149 results on '"Qiao, Hong"'
Search Results
2. Vertically Aligned MoS2 with In-Plane Selectively Cleaved Mo–S Bond for Hydrogen Production
- Author
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Yang Li, Jing Zhang, Huabin Zhang, Xin Wu, Jian Zhang, Shouwei Zuo, and Qiao-Hong Li
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Materials science ,Mechanical Engineering ,Bioengineering ,02 engineering and technology ,General Chemistry ,Electronic structure ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Catalysis ,chemistry.chemical_compound ,Crystallography ,Adsorption ,chemistry ,Vacancy defect ,General Materials Science ,Metal-organic framework ,0210 nano-technology ,Molybdenum disulfide ,Coordination geometry ,Hydrogen production - Abstract
Perturbing the periodic electronic structure of the MoS2 basal plane via vacancy engineering offers an opportunity to explore its intrinsic activity. A significant challenge is the design of vacancy states, which include its type, distribution, and accessibility. Here, well-dispersed and vertically aligned MoS2 nanosheets with an in-plane selectively cleaved Mo-S bond on a carbon matrix (c-MoS2-C) have been prepared by a self-engaged strategy, which synergistically realizes uniform vacancy manufacturing and three-dimensional (3D) self-assembly of the defective MoS2 nanosheets. X-ray adsorption spectroscopy investigation confirms that the cleaved MoS2 basal plane generates newly active edge sites, where the Mo centers feature unsaturated coordination geometry. Theoretical calculations reveal that the exposed interior edge Mo sites represent new active centers for hydrogen adsorption/desorption. As expected, the synthesized c-MoS2-C exhibits markedly enhanced hydrogen evolution activity and superior stability. This in-plane activation strategy could be extended to other types of transition-metal dichalcogenides and catalytic reaction systems.
- Published
- 2021
3. Transcriptomic and anatomic profiling reveal the germination process of different wheat varieties in response to waterlogging stress
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Liu Yuanhai, Qiao Hong, Xiling Chen, Ying Zhang, Xingqi Ou, Xing Liu, Changwei Shen, Wang Zijuan, Jingping Yuan, Fei Wang, and Xiujuan Ren
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0106 biological sciences ,0301 basic medicine ,lcsh:QH426-470 ,Starch ,Germination ,Differentially expressed gene ,Biology ,01 natural sciences ,Endosperm ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,Gene Expression Regulation, Plant ,Stress, Physiological ,Genetics ,Amyloplast ,Cultivar ,Genetics (clinical) ,Triticum ,Abiotic component ,food and beverages ,Waterlogged ,Floods ,Horticulture ,lcsh:Genetics ,030104 developmental biology ,Gene Ontology ,Phenotype ,Anatomical structure ,chemistry ,Seeds ,Wheat ,Carbohydrate Metabolism ,010606 plant biology & botany ,Waterlogging (agriculture) ,Research Article - Abstract
Background Waterlogging is one of the most serious abiotic stresses affecting wheat-growing regions in China. Considerable differences in waterlogging tolerance have been found among different wheat varieties, and the mechanisms governing the waterlogging tolerance of wheat seeds during germination have not been elucidated. Results The results showed no significant difference between the germination rate of ‘Bainong 207’ (BN207) (after 72 h of waterlogging treatment) and that of the control seeds. However, the degree of emulsification and the degradation rate of endosperm cells under waterlogging stress were higher than those obtained with the control treatment, and the number of amyloplasts in the endosperm was significantly reduced by waterlogging. Transcriptomic data were obtained from seed samples (a total of 18 samples) of three wheat varieties, ‘Zhoumai 22’ (ZM22), BN207 and ‘Bainong 607’ (BN607), subjected to the waterlogging and control treatments. A comprehensive analysis identified a total of 2775 differentially expressed genes (DEGs). In addition, an analysis of the correlations among the expression difference levels of DEGs and the seed germination rates of the three wheat varieties under waterlogging stress revealed that the relative expression levels of 563 and 398 genes were positively and negatively correlated with the germination rate of the wheat seeds, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the difference in the waterlogging tolerance among the three wheat varieties was related to the abundance of key genes involved in the glycolysis pathway, the starch and sucrose metabolism pathway, and the lactose metabolism pathway. The alcohol dehydrogenase (ADH) gene in the endosperm of BN607 was induced immediately after short-term waterlogging, and the energy provided by the glycolysis pathway enabled the BN607 seeds to germinate as early as possible; in addition, the expression of the AP2/ERF transcription factor was upregulated to further enhance the waterlogging tolerance of this cultivar. Conclusions Taken together, the results of this study help elucidate the mechanisms through which different wheat varieties respond to waterlogging stress during germination.
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- 2020
4. Privet golden leaves adapt unexpectedly well to light changes
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Zhong-Wei Zhang, Li-Hua Dong, Bo Huang, Shu Yuan, Ming Yuan, Yong Yang, Chunbang Ding, Yang-Er Chen, Qiao-Hong Han, and Chao Hu
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chemistry.chemical_classification ,Canopy ,biology ,ved/biology ,Privet ,ved/biology.organism_classification_rank.species ,Plant physiology ,Plant Science ,Horticulture ,biology.organism_classification ,Photosynthetic capacity ,Shrub ,chemistry.chemical_compound ,chemistry ,Chlorophyll ,Ornamental plant ,Carotenoid ,Biotechnology - Abstract
Golden-leaf privet (Ligustrum × vicaryi) is widely used as a horticultural shrub because of its upper golden leaves, but its lower leaves are green. However, the putative mechanisms of its upper golden leaves and the leaf color changes in response to light shifts have not been well studied so far. Here, chlorophylls (Chl), carotenoids, and Chl precursors from both golden and green leaves grown in full sunlight (approximately 1200 μmol photons m−2 s−1 at noon) or low-light conditions (180 μmol m−2 s−1) were determined spectrophotometrically. In addition, their gas exchange parameters and Chl fluorescence were measured in situ. Metabolic flux analysis of chlorophyll intermediates indicated that the conversion of prochlorophyllide to chlorophyllide was significantly blocked in golden leaves when compared with green leaves. Green leaves showed higher photosynthetic capacity in low light than golden leaves, but golden leaves presented unexpectedly stronger photosynthetic capacity and lower reactive oxygen species accumulation under the high-light condition. Furthermore, golden leaves showed a higher level of nonphotochemical quenching (NPQ) after the light-to-dark shift and presented a stronger adaptive ability to a broad range of light environments. Higher NPQ values and less oxidative damage in golden leaves may be correlated with their higher carotenoid levels. The results imply that lower chlorophyll levels and higher carotenoid levels in canopy leaves may help privet plants acclimate better to illumination changes. This study demonstrates the key role of irradiance in generating the two types of Ligustrum × vicaryi leaves and sheds a light on cultivation of other ornamental foliage plants.
- Published
- 2020
5. Application of Hydrogen Proton Magnetic Resonance Technology Combined with Brain Neurometabolite Analysis in the Treatment of Cognitive Impairment Caused by Type 2 Diabetes Mellitus
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Changhao Yin, Xu Lian, Siou Li, Qiao Hong, and Weina Zhao
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Adult ,Male ,medicine.medical_specialty ,Medial cortex ,Proton Magnetic Resonance Spectroscopy ,Prefrontal Cortex ,Type 2 diabetes ,White matter ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Cognitive Dysfunction ,Prefrontal cortex ,Aged ,Aspartic Acid ,business.industry ,Type 2 Diabetes Mellitus ,Cognition ,Middle Aged ,medicine.disease ,Treatment Outcome ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,030220 oncology & carcinogenesis ,Female ,Surgery ,Neurology (clinical) ,Glycated hemoglobin ,Protons ,business ,030217 neurology & neurosurgery ,Hydrogen - Abstract
This study used hydrogen proton magnetic resonance imaging to detect the changes of white matter and the medial cortex in the prefrontal cortex of patients with type 2 diabetes, analyzed its relationship with cognitive function and blood glucose level, and discussed the recognition of patients with type 2 diabetes from the perspective of brain metabolism. We discuss the neural mechanisms affected by the disorder. The experiment recruited 65 volunteers, including 32 control subjects and 33 patients with type 2 diabetes. All volunteers underwent clinical cognitive function and psychological evaluation, including a simple intelligent mental state examination scale, digital breadth test, Raven intelligence test, Flanker paradigm experiment, connection test, auditory word learning test, depression self-evaluation scale, and anxiety self-rating scale. All subjects underwent multivoxel proton magnetic resonance scanning, and the spectral data were processed and metabolite concentration analysis was completed by Functool software. The detected regions of interest included the bilateral prefrontal white matter and bilateral prefrontal cortex. This study found that the N-acetylaspartate (NAA) and NAA/myo-inositol (MI) of the right prefrontal cortex were reduced, the right prefrontal white matter choline-containing compounds increased, and the MI of the bilateral prefrontal cortex increased in the type 2 diabetes group compared with the control group. The NAA value of the right prefrontal cortex in the type 2 diabetes group was negatively correlated with the glycated hemoglobin concentration. The study found that the right prefrontal cortex NAA value of patients with type 2 diabetes was negatively correlated with the glycated hemoglobin concentration, reflecting that recent blood glucose levels can affect the changes of brain metabolites, and reasonable control of blood glucose can effectively delay brain neurons caused by diabetes.
- Published
- 2020
6. Changes of phenolic compounds, antioxidant capacities, and inhibitory effects on digestive enzymes of kiwifruits (Actinidia chinensis) during maturation
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Li Zhao, Xi-Rui Nie, Qing Zhang, Ding-Tao Wu, Wen Qin, Hong-Yi Li, Si-Yu Wei, Qiao-Hong Han, and Suqing Li
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Antioxidant ,Actinidia chinensis ,General Chemical Engineering ,medicine.medical_treatment ,01 natural sciences ,Industrial and Manufacturing Engineering ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Chlorogenic acid ,medicine ,Caffeic acid ,Gallic acid ,Food science ,Safety, Risk, Reliability and Quality ,Procyanidin B2 ,chemistry.chemical_classification ,Neochlorogenic acid ,biology ,010401 analytical chemistry ,04 agricultural and veterinary sciences ,biology.organism_classification ,040401 food science ,0104 chemical sciences ,Enzyme ,chemistry ,Food Science - Abstract
Phenolic compounds are considered the main bioactive components in kiwifruit. In order to well understand the accumulation pattern of health-beneficial phenolics, and to obtain high-quality kiwifruits with health-promoting characteristics, the changes of physicochemical properties, phenolic compounds, antioxidant capacities, and inhibitory effects on digestive enzymes of “Donghong” kiwifruits during maturation were systematically investigated. Noticeable variations in physicochemical properties and phenolic profiles were observed throughout the maturation stages of “Donghong” kiwifruit. According to the HPLC analysis, phenolic compounds, including chlorogenic acid, (−)-epicatechin, procyanidin B2, quercetin-3-O-rhamnoside, gallic acid, neochlorogenic acid, and caffeic acid, were found in “Donghong” kiwifruit, while chlorogenic acid was the most abundant phenolic compound. Considering the accumulation patterns of both total phenolics and soluble solids content, the optimum harvest time of kiwifruit with relatively high level of health-beneficial components was determined. Furthermore, “Donghong” kiwifruit exerted remarkable antioxidant capacities, and inhibitory effects on pancreatic lipase and α-glucosidase. Indeed, the Pearson’s correlation showed that chlorogenic acid, caffeic acid, (−)-epicatechin, and quercetin-3-O-rhamnoside could be major contributors to the antioxidant activity and inhibitory effects on digestive enzymes. Results are beneficial for better understanding of the accumulation patterns of health-beneficial phenolic compounds, which can aid in the targeting of specific developmental stages with an optimal phenolic profile for the production of health-beneficial products.
- Published
- 2020
7. Physicochemical characteristics and antioxidant activities of non-starch polysaccharides from different kiwifruits
- Author
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Li Zhao, Wen Liu, Gang Du, Qiao-Hong Han, Suqing Li, Qin Yuan, Ding-Tao Wu, Hong-Yi Li, Yuan Fu, Qing Zhang, and Wen Qin
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Arabinose ,Antioxidant ,Chemical Phenomena ,medicine.medical_treatment ,Actinidia ,02 engineering and technology ,Nitric Oxide ,Polysaccharide ,Biochemistry ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,Species Specificity ,Functional food ,Polysaccharides ,Structural Biology ,medicine ,Monosaccharide ,Benzothiazoles ,Food science ,Molecular Biology ,030304 developmental biology ,Actinidia deliciosa ,chemistry.chemical_classification ,0303 health sciences ,biology ,Viscosity ,Monosaccharides ,Extraction (chemistry) ,General Medicine ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Molecular Weight ,Hot water extraction ,chemistry ,Sulfonic Acids ,0210 nano-technology - Abstract
Non-starch polysaccharides are considered the main bioactive ingredients in kiwifruits. In order to well understand the chemical structures and antioxidant activities of non-starch polysaccharides from different varieties of kiwifruits (KPSs), the physicochemical characteristics and antioxidant activities of KPSs extracted by hot water extraction from Actinidia deliciosa cv. Hayward, A. chinensis cv. Hort16A, A. chinensis cv. Jinshi, A. chinensis cv. Hongshi, A. polygama , A. macrosperma , and A. arguta were investigated and compared. Results showed that extraction yields and contents of total uronic acids in KPSs ranged from 2.60% to 5.52%, and from 35.07% to 42.20%, respectively. Molecular weights and intrinsic viscosities of KPSs ranged from 1.405 × 10 5 to 1.620 × 10 6 Da, and from 0.34 dL/g to 1.24 dL/g, respectively. The dominant constituent monosaccharides of KPSs were galacturonic acid, arabinose, and galactose. Furthermore, KPSs from kiwifruits, especially KPSs extracted from A. arguta , exerted remarkable 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid and nitric oxide radical scavenging activities, which might be partially attributed to their high content of unmethylated galacturonic acids. Results are helpful for better understanding of the chemical structures and antioxidant activities of KPSs, and KPSs had potential to be further explored as natural antioxidants for the application in the functional food industry.
- Published
- 2019
8. A novel curcumin analog inhibits canonical and non-canonical functions of telomerase through STAT3 and NF-κB inactivation in colorectal cancer cells
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Seyung S Chung, Pranabananda Dutta, Nathaniel Chard, Jaydutt V. Vadgama, Guanglin Chen, Yong Wu, and Qiao-Hong Chen
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0301 basic medicine ,cancer stem cells ,Telomerase ,Caspase 3 ,colorectal cancer ,NF-κB ,STAT3 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cancer stem cell ,Telomerase reverse transcriptase ,curcumin analog ,biology ,Clusterin ,CD44 ,3. Good health ,030104 developmental biology ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Curcumin ,Research Paper - Abstract
Curcumin is a biologically active polyphenol that exists in Indian spice turmeric. It has been reported that curcumin exerted anti-inflammatory, anti-oxidant and anti-cancer effects in numerous in vitro and in vivo studies. However, it is not well-understood the molecular mechanism of curcumin for the cancer stem cells and telomerase in colorectal cancer. In this study, compound 19, a nitrogen-containing curcumin analog, was used to treat human colorectal cancer cells. Compound 19 showed a greater anti-proliferative activity than curcumin while displayed no significant toxicity toward normal human colon epithelial cells. Compound 19 exerted anti-inflammatory activities by deactivating STAT3 and NF-κB. In cancer stem cell populations, CD44, Oct-4 and ALDHA1 expressions were abolished upon treating with compound 19. Cancer stem cell biomarkers CD51 and CD133 positive populations were reduced and telomerase activities were decreased with the reduced STAT3 binding to hTERT promoters. This means compound 19 dually inhibits canonical and non-canonical functions of telomerase. Furthermore, compound 19 treatments induced cell cycle arrest at G1 phase and apoptosis. Human apoptosis-related array screening revealed that activated caspase 3, catalase, clusterin and cytochrome C led to apoptosis. Taken together, our data suggest that compound 19 can be a novel therapeutic agent for metastatic colorectal cancer by concurrently targeting STAT3 and NF-κB signaling pathways.
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- 2019
9. Targeting of PP2Cδ By a Small Molecule C23 Inhibits High Glucose-Induced Breast Cancer Progression In Vivo
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Xiaoting Yu, Yong Wu, Roshni Iyer, Qiao-Hong Chen, Kevin T Kemp nd, Ying-Li Wu, Guanglin Chen, Qiongyu Hao, Xianghua Yi, Kytai T. Nguyen, Ke Wu, Guangdi Wang, Donghui Zhu, Shilong Zheng, Zhimin Huang, Jaydutt V. Vadgama, and Yahya Elshimali
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Models, Molecular ,0301 basic medicine ,Physiology ,Clinical Biochemistry ,Cell ,Biochemistry ,Mice ,chemistry.chemical_compound ,Enzyme Inhibitors ,Phosphorylation ,General Environmental Science ,biology ,NF-kappa B ,Acetylation ,Protein Phosphatase 2C ,Original Research Communications ,medicine.anatomical_structure ,Disease Progression ,Female ,Growth inhibition ,Curcumin ,Antineoplastic Agents ,Breast Neoplasms ,03 medical and health sciences ,Hsp27 ,Cell Line, Tumor ,Heat shock protein ,medicine ,Animals ,Humans ,Molecular Biology ,Protein kinase C ,Glycogen Synthase Kinase 3 beta ,030102 biochemistry & molecular biology ,Cell growth ,Cancer ,NF-κB ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,Glucose ,030104 developmental biology ,chemistry ,Hyperglycemia ,biology.protein ,Cancer research ,General Earth and Planetary Sciences ,Tumor Suppressor Protein p53 ,Reactive Oxygen Species - Abstract
Aims: Epidemiologic evidence indicates that diabetes may increase risk of breast cancer (BC) and mortality in patients with cancer. The pathophysiological relationships between diabetes and cancer are not fully understood, and personalized treatments for diabetes-associated BC are urgently needed. Results: We observed that high glucose (HG), via activation of nuclear phosphatase PP2Cδ, suppresses p53 function, and consequently promotes BC cell proliferation, migration, and invasion. PP2Cδ expression is higher in tumor tissues from BC patients with hyperglycemia than those with normoglycemia. The mechanisms underlying HG stimulation of PP2Cδ involve classical/novel protein kinase-C (PKC) activation and GSK3β phosphorylation. Reactive oxygen species (ROS)/NF-κB pathway also mediates HG induction of PP2Cδ. Furthermore, we identified a 1,5-diheteroarylpenta-1,4-dien-3-one (Compound 23, or C23) as a novel potent PP2Cδ inhibitor with a striking cytotoxicity on MCF-7 cells through cell-based screening assay for growth inhibition and activity of a group of curcumin mimics. Beside directly inhibiting PP2Cδ activity, C23 blocks HG induction of PP2Cδ expression via heat shock protein 27 (HSP27) induction and subsequent ablation of ROS/NF-κB activation. C23 can thus significantly block HG-triggered inhibition of p53 activity, leading to the inhibition of cancer cell proliferation, migration, and invasion. In addition, hyperglycemia promotes BC development in diabetic nude mice, and C23 inhibits the xenografted BC tumor growth. Conclusions and Innovation: Our findings elucidate mechanisms that may have contributed to diabetes-associated BC progression, and provide the first evidence to support the possible alternative therapeutic approach to BC patients with diabetes. Antioxid. Redox Signal. 30, 1983-1998.
- Published
- 2019
10. Synthesis and antiproliferative evaluation of new zampanolide mimics
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James D. White, Guangdi Wang, Guanglin Chen, Manee Patanapongpibul, Qiang Zhang, Ziran Jiang, Qiao-Hong Chen, and Shilong Zheng
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Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,Structure-Activity Relationship ,chemistry.chemical_compound ,DU145 ,In vivo ,Tumor Cells, Cultured ,Side chain ,Humans ,Structure–activity relationship ,Physical and Theoretical Chemistry ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Cell growth ,Organic Chemistry ,Combinatorial chemistry ,0104 chemical sciences ,chemistry ,Cancer cell ,Macrolides ,Bioisostere ,Drug Screening Assays, Antitumor ,Lead compound - Abstract
(–)–Zampanolide is a marine microtubule-stabilizing macrolide that has been shown by in vitro experiments to be a promising anticancer lead compound. Through its unique covalent-binding with β-tubulin, zampanolide exhibits cytotoxic potency towards multi-drug resistant cancer cells that is superior to paclitaxel. However, the limited availability of zampanolide impedes its further in vivo evaluation as a viable drug candidate. Zampanolide is envisioned to become more drug-like if its chemically fragile side chain can be stabilized; hence, this project aims to develop mimics of zampanolide with a stable side chain using straightforward synthetic methods. To this end, twelve novel zampanolide mimics (51-62) with conjugated and planar side chains have been synthesized via a 24-step sequence for each mimic from commercially available 2-butyn-1-ol as starting material. A Horner-Wadsworth-Emmons reaction incorporates the α,β-unsaturated ketone side chain and also closes the core macrocycle. WST-1 cell proliferation assays in three docetaxel-sensitive and two docetaxel-resistant human prostate cancer cell models confirm that a suitably designed side chain can serve as a bioisostere for the N-acyl hemiaminal side chain in zampanolide. Mimic 52 with a 17R chiral center was identified as the optimal candidate with IC(50) values of 0.29–0.46 μM against both docetaxel-sensitive (PC-3 and DU145) and docetaxel-resistant prostate cancer cell lines (PC-3/DTX and DU145/DTX). Zampanolide mimic 52 exhibited equivalent antiproliferative potency towards both docetaxel-sensitive and docetaxel-resistant cell lines, with relative resistance in the range of 0.9–1.6.
- Published
- 2019
11. Select β- and γ-branched 1-alkylpyrazol-4-yl methylcarbamates exhibit high selectivity for inhibition of Anopheles gambiae versus human acetylcholinesterase
- Author
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Paul R. Carlier, Qiao-Hong Chen, Astha Verma, James M. Mutunga, Jianyong Li, Jeffrey R. Bloomquist, Fan Tong, Alex M. Shimozono, Dawn M. Wong, Max Totrov, Jasmin Müller, and Rafique Islam
- Subjects
0301 basic medicine ,Carbamate ,Strain (chemistry) ,Molecular model ,biology ,Chemistry ,Aché ,Stereochemistry ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Aryl ,Anopheles gambiae ,General Medicine ,biology.organism_classification ,Acetylcholinesterase ,language.human_language ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,medicine ,language ,Selectivity ,Agronomy and Crop Science - Abstract
The widespread emergence of pyrethroid-resistant Anopheles gambiae has intensified the need to find new contact mosquitocides for indoor residual spraying and insecticide treated nets. With the goal of developing new species-selective and resistance-breaking acetylcholinesterase (AChE)-inhibiting mosquitocides, in this report we revisit the effects of carbamate substitution on aryl carbamates, and variation of the 1-alkyl group on pyrazol-4-yl methylcarbamates. Compared to aryl methylcarbamates, aryl dimethylcarbamates were found to have lower selectivity for An. gambiae AChE (AgAChE) over human AChE (hAChE), but improved tarsal contact toxicity to G3 strain An. gambiae. Molecular modeling studies suggest the lower species-selectivity of the aryl dimethylcarbamates can be attributed to a less flexible acyl pocket in AgAChE relative to hAChE. The improved tarsal contact toxicity of the aryl dimethylcarbamates relative to the corresponding methylcarbamates is attributed to a range of complementary phenomena. With respect to the pyrazol-4-yl methylcarbamates, the previously observed low An. gambiae-selectivity of compounds bearing α-branched 1-alkyl groups was improved by employing β- and γ-branched 1-alkyl groups. Compounds 22a (cyclopentylmethyl), 21a (cyclobutylmethyl), and 26a (3-methylbutyl) offer 250-fold, 120-fold, and 96-fold selectivity, respectively, for inhibition of AgAChE vs. hAChE. Molecular modeling studies suggests the high species-selectivity of these compounds can be attributed to the greater mobility of the W84 sidechain in the choline-binding site of AgAChE, compared to that of W86 in hAChE. Compound 26a has reasonable contact toxicity to G3 strain An. gambiae (LC50 = 269 μg/mL) and low cross-resistance to Akron strain (LC50 = 948 μg/mL), which bears the G119S resistance mutation.
- Published
- 2018
12. Anticancer Agents
- Author
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Qiao-Hong Chen
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chemistry.chemical_compound ,Virtual screening ,Natural product ,chemistry ,Design synthesis ,Computer science ,Docking (molecular) ,Drug discovery ,Computational biology ,Immune modulation ,Protein degradation ,Chemical synthesis - Published
- 2021
13. 1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel
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Karan Modi, Michael Kurtz, Ashakumary Lakshmikuttyamma, Qiao-Hong Chen, Scott Lawson, Deepthi Tumuluri, Guanglin Chen, G. Cristina Brailoiu, and Inga Rekhtman
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0301 basic medicine ,medicine.medical_treatment ,Triple Negative Breast Neoplasms ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,curcumin ,Breast ,lcsh:QH301-705.5 ,Spectroscopy ,Triple-negative breast cancer ,Chemistry ,Drug Synergism ,General Medicine ,Computer Science Applications ,Mitochondria ,Gene Expression Regulation, Neoplastic ,Cytokine ,Paclitaxel ,030220 oncology & carcinogenesis ,triple-negative breast cancer ,Female ,Benzopyrone ,Epithelial-Mesenchymal Transition ,Cell Survival ,Down-Regulation ,Antineoplastic Agents ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Cell Proliferation ,IL-6 ,Interleukin-6 ,Organic Chemistry ,Epithelial Cells ,In vitro ,Bioavailability ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cell culture ,Chromones ,Cancer research ,Curcumin ,Reactive Oxygen Species - Abstract
Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial&ndash, mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.
- Published
- 2020
14. Preparation and Characterization of Temperature-Adjusting Asphalt with Diatomite-Supported PEG as an Additive
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Jia Jian, Qiao Hong, Yanmin Wang, Zhi-Min Liu, Huadong Sun, and Huiru Wang
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Materials science ,technology, industry, and agriculture ,0211 other engineering and technologies ,020101 civil engineering ,macromolecular substances ,02 engineering and technology ,Building and Construction ,Polyethylene glycol ,0201 civil engineering ,chemistry.chemical_compound ,chemistry ,Mechanics of Materials ,Asphalt ,021105 building & construction ,PEG ratio ,General Materials Science ,Composite material ,Civil and Structural Engineering - Abstract
To solve the rutting damage of asphaltic pavement and the adverse effects of urban heat islands, diatomite-adsorbing polyethylene glycol (PEG), that is, diatomite-supported PEG (PEG/diatomi...
- Published
- 2020
15. Effect of Low Temperature on Chlorophyll Biosynthesis and Chloroplast Biogenesis of Rice Seedlings during Greening
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Shu Yuan, Yuqing Zhao, Lijun Zhou, Shiling Feng, Chunbang Ding, Ming Yuan, Yan Huang, Tao Chen, Jinqiu Liao, Zhong-Wei Zhang, Qiao-Hong Han, and Yang-Er Chen
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Chlorophyll ,0106 biological sciences ,0301 basic medicine ,Chloroplasts ,Photosystem II ,01 natural sciences ,lcsh:Chemistry ,chemistry.chemical_compound ,Gene Expression Regulation, Plant ,Malondialdehyde ,Plastids ,Intramolecular Transferases ,lcsh:QH301-705.5 ,Spectroscopy ,Cell Death ,biology ,epidermal characteristics ,Temperature ,food and beverages ,General Medicine ,Computer Science Applications ,Chloroplast ,Horticulture ,chloroplast biogenesis ,Thylakoid ,oryza sativa l ,Oxidoreductases Acting on CH-CH Group Donors ,Down-Regulation ,Lyases ,Photosystem I ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Greening ,Microscopy, Electron, Transmission ,Protochlorophyllide ,Oryza sativa L ,Physical and Theoretical Chemistry ,Molecular Biology ,chlorophyll biosynthesis ,Photosystem I Protein Complex ,Cold-Shock Response ,Organic Chemistry ,chilling stress ,Photosystem II Protein Complex ,Oryza ,Aminolevulinic Acid ,biology.organism_classification ,Plant Leaves ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Seedlings ,Seedling ,Plant Stomata ,Epidermis ,Reactive Oxygen Species ,010606 plant biology & botany - Abstract
Rice (Oryza sativa L.) frequently suffers in late spring from severe damage due to cold spells, which causes the block of chlorophyll biosynthesis during early rice seedling greening. However, the inhibitory mechanism by which this occurs is still unclear. To explore the responsive mechanism of rice seedlings to low temperatures during greening, the effects of chilling stress on chlorophyll biosynthesis and plastid development were studied in rice seedlings. Chlorophyll biosynthesis was obviously inhibited and chlorophyll accumulation declined under low temperatures during greening. The decrease in chlorophyll synthesis was due to the inhibited synthesis of &delta, aminolevulinic acid (ALA) and the suppression of conversion from protochlorophyllide (Pchlide) into chlorophylls (Chls). Meanwhile, the activities of glutamate-1-semialdehyde transaminase (GSA-AT), Mg-chelatase, and protochlorophyllide oxidoreductase (POR) were downregulated under low temperatures. Further investigations showed that chloroplasts at 18 °, C had loose granum lamellae, while the thylakoid and lamellar structures of grana could hardly develop at 12 °, C after 48 h of greening. Additionally, photosystem II (PSII) and photosystem I (PSI) proteins obviously declined in the stressed seedlings, to the point that the PSII and PSI proteins could hardly be detected after 48 h of greening at 12 °, C. Furthermore, the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) and cell death were all induced by low temperature. Chilling stress had no effect on the development of epidermis cells, but the stomata were smaller under chilling stress than those at 28 °, C. Taken together, our study promotes more comprehensive understanding in that chilling could inhibit chlorophyll biosynthesis and cause oxidative damages during greening.
- Published
- 2020
16. Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties
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Xue-Lian Yang, Qiao-Hong Liu, Hua-Li Yang, Pei Cai, Xiao-Bing Wang, Ling-Yi Kong, and Si-Qiang Fang
- Subjects
0301 basic medicine ,Antioxidant ,DPPH ,medicine.medical_treatment ,Cholinergic Agents ,Pharmacology ,PC12 Cells ,Antioxidants ,Cell Line ,Mice ,Protein Aggregates ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Alzheimer Disease ,Drug Discovery ,medicine ,Animals ,Butylated hydroxytoluene ,Donepezil ,Amyloid beta-Peptides ,ABTS ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,General Medicine ,Butylated Hydroxytoluene ,Acetylcholinesterase ,Rats ,Neuroprotective Agents ,030104 developmental biology ,chemistry ,Indans ,Cholinesterase Inhibitors ,Trolox ,Monoamine oxidase B ,030217 neurology & neurosurgery ,medicine.drug - Abstract
The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075 μM for eeAChE and 0.75 μM for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4 μM for hMAO-B), excellent antioxidant activity (71.7 μM of IC50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, hAChE-induced Aβ aggregation. Moreover, 7d possessed neuroprotective potency against H2O2-induced oxidative damage on PC12 cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD.
- Published
- 2018
17. Structure-activity relationship and pharmacokinetic studies of 3-O-substitutedflavonols as anti-prostate cancer agents
- Author
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Aaron Gonzalez, Ryan Fong, Guanglin Chen, Pravien Rajaram, Qiang Zhang, Shanchun Guo, Maizie Lee, Guangdi Wang, Xiang Li, Changde Zhang, Shilong Zheng, and Qiao-Hong Chen
- Subjects
Male ,0301 basic medicine ,Flavonols ,Antineoplastic Agents ,Article ,Pyrrolidine ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Humans ,Potency ,Structure–activity relationship ,Cells, Cultured ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Prostatic Neoplasms ,General Medicine ,medicine.disease ,Rats ,Bioavailability ,030104 developmental biology ,Mechanism of action ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Drug Screening Assays, Antitumor ,medicine.symptom ,Linker - Abstract
Thirty-eight 3-O-substituted-3′,4′-dimethoxyflavonols and twenty-five 3-O-substituted-3′,4′,7-trimethoxyflavonols have been synthesized for systematic investigation on the structure-activity relationships of 3-O-substituted-3′,4′-dimethoxyflavonols in three human prostate cancer cell models. Our findings indicate that incorporation of an appropriate amino group to 3-OH of 3′,4′-dimethoxyflavonol and 3′,4′,7-trimethoxyflavonol through a 3- to 5-carbon linker can substantially improve the in vitro antiproliferative potency in three human prostate cancer cell models, but not in two non-neoplastic human epithelial cell models (MCF 10A and PWR-1E). 1-Methylpiperazine, pyrrolidine, and dibutylamine are optimal terminal amine groups that, in combination with a 3- to 5-carbon linker, are notably beneficial to the anti-proliferative potency of 3-O-substituted-3′,4′-dimethoxyflavonols. It is worth noting that 3-O-(4-methylpiperazin-1-yl)propyl-3′,4′,7-trimethoxyflavonol (76) induces PC-3 cell death in a completely different way from 3-O-pyrrolidinopentyl-3′,4′,7-trimethoxyflavonol (81) even though they belong to 3-O-substituted-3′,4′,7-trimethoxyflavonols and exhibit similar potency in inhibiting PC-3 cell proliferation, suggesting that the mechanism of action for each specific 3-O-substitutedflavonol varies with different amino moiety. 3-O-(N,N-Dibutylamino)propyl-3′,4′-dimethoxyflavonol (42) emerged as the most promising derivative due to its substantially improved potency in cell models, superior bioavailability in rats, and good selectivity of inhibiting prostate cancer cell proliferation over non-neoplastic human epithelial cell proliferation.
- Published
- 2018
18. 2D Boron Imidazolate Framework Nanosheets with Electrocatalytic Applications for Oxygen Evolution and Carbon Dioxide Reduction Reaction
- Author
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Shu-Mei Chen, Tianhua Zhou, Chris Ritchie, Yonghua Du, Min Liu, Tian Wen, Qiao-Hong Li, and Jian Zhang
- Subjects
Materials science ,Oxygen evolution ,chemistry.chemical_element ,02 engineering and technology ,General Chemistry ,Overpotential ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,7. Clean energy ,0104 chemical sciences ,Biomaterials ,chemistry.chemical_compound ,Chemical engineering ,chemistry ,13. Climate action ,Imidazolate ,General Materials Science ,Metal-organic framework ,0210 nano-technology ,Boron ,Faraday efficiency ,Biotechnology ,Nanosheet ,Electrochemical reduction of carbon dioxide - Abstract
Ultrathin 2D materials possess unique properties that translate to enhanced efficiency as electrocatalysts, stimulating research toward methodologies that support their preparation. Herein, a two-step strategy is reported that involves the preparation of the new boron imidazolate framework (BIF-73) which is subsequently utilized as a precursor to yield the crystalline 2D nanosheet material (Fe@BIF-73-NS) via post-synthetic modification. This new electrocatalytic material stabilizes ultra-small (Fe2 O3 ) fragments resulting in an excellent electrocatalytic performance for the oxygen evolution reaction (OER: lower overpotential with 291 mV at the current density of 10 mA cm-2 ) and carbon dioxide reduction reaction (faradaic efficiency of CO reaching 88.6% at -1.8 V vs Ag/AgCl) without the need for noble metals. Additionally, theoretical calculations and microscopy reveal that the superior OER performance can be attributed to the increased exposure of binding sites within the material to which the catalytically active Fe3+ centers are bound through a post-synthetic modification procedure. A red-shift of the Fermi level around the valence band is observed and is proposed to be a result of the aforementioned interactions. This work opens an avenue toward the development of 2D functional metal organic framework nanosheets for energy conversion applications.
- Published
- 2019
19. New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation
- Author
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Guangdi Wang, Qiang Zhang, Ziran Jiang, Guanglin Chen, and Qiao-Hong Chen
- Subjects
Male ,natural product ,synthesis ,zampanolide ,Pharmaceutical Science ,Antineoplastic Agents ,Docetaxel ,01 natural sciences ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,stomatognathic system ,Biomimetics ,Drug Discovery ,Side chain ,Tumor Cells, Cultured ,Humans ,Physical and Theoretical Chemistry ,Cell Proliferation ,chemistry.chemical_classification ,Natural product ,010405 organic chemistry ,Organic Chemistry ,Prostatic Neoplasms ,Combinatorial chemistry ,3. Good health ,0104 chemical sciences ,anticancer agent ,chemistry ,Chemistry (miscellaneous) ,Covalent bond ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Drug Design ,Hemiaminal ,Molecular Medicine ,Bioisostere ,Macrolides ,Sharpless asymmetric dihydroxylation ,Yamaguchi esterification ,Lactone - Abstract
Zampanolide is a promising microtubule-stabilizing agent (MSA) with a unique chemical structure. It is superior to the current clinically used MSAs due to the covalent nature of its binding to &beta, tubulin and high cytotoxic potency toward multidrug-resistant cancer cells. However, its further development as a viable drug candidate is hindered by its limited availability. More importantly, conversion of its chemically fragile side chain into a stabilized bioisostere is envisioned to enable zampanolide to possess more drug-like properties. As part of our ongoing project aiming to develop its mimics with a stable side chain using straightforward synthetic approaches, 2-fluorobenzyl alcohol was designed as a bioisosteric surrogate for the side chain based on its binding conformation as confirmed by the X-ray structure of tubulin complexed with zampanolide. Two new zampanolide mimics with the newly designed side chain have been successfully synthesized through a 25-step chemical transformation for each. Yamaguchi esterification and intramolecular Horner&ndash, Wadsworth&ndash, Emmons condensation were used as key reactions to construct the lactone core. The chiral centers at C17 and C18 were introduced by the Sharpless asymmetric dihydroxylation. Our WST-1 cell proliferation assay data in both docetaxel-resistant and docetaxel-naive prostate cancer cell lines revealed that compound 6 is the optimal mimic and the newly designed side chain can serve as a bioisostere for the chemically fragile N-acetyl hemiaminal side chain in zampanolide.
- Published
- 2019
20. PP2Cδ inhibits p300-mediated p53 acetylation via ATM/BRCA1 pathway to impede DNA damage response in breast cancer
- Author
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Jieqing Li, Ke Wu, Guanglin Chen, Qun Li, Jonathan R. Pollack, Yong Wu, Yahya Elshimali, Qiao-Hong Chen, Donghui Zhu, Wei Cao, Jay Vadgama, and Qiongyu Hao
- Subjects
endocrine system diseases ,DNA damage ,Phosphatase ,Mice, Nude ,Apoptosis ,Breast Neoplasms ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,medicine.disease_cause ,Dephosphorylation ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Phosphorylation ,skin and connective tissue diseases ,Research Articles ,Cancer ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,BRCA1 Protein ,Chemistry ,SciAdv r-articles ,Life Sciences ,Acetylation ,3. Good health ,Cell biology ,Protein Phosphatase 2C ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Female ,Tumor Suppressor Protein p53 ,Carcinogenesis ,E1A-Associated p300 Protein ,DNA ,Research Article ,DNA Damage ,Signal Transduction - Abstract
Aberrant PP2Cδ inhibits p300-mediated p53 acetylation and activation via the ATM/BRCA1 pathway, leading to cancer progression., Although nuclear type 2C protein phosphatase (PP2Cδ) has been demonstrated to be pro-oncogenic with an important role in tumorigenesis, the underlying mechanisms that link aberrant PP2Cδ levels with cancer development remain elusive. Here, we found that aberrant PP2Cδ activity decreases p53 acetylation and its transcriptional activity and suppresses doxorubicin-induced cell apoptosis. Mechanistically, we show that BRCA1 facilitates p300-mediated p53 acetylation by complexing with these two proteins and that S1423/1524 phosphorylation is indispensable for this regulatory process. PP2Cδ, via dephosphorylation of ATM, suppresses DNA damage–induced BRCA1 phosphorylation, leading to inhibition of p300-mediated p53 acetylation. Furthermore, PP2Cδ levels correlate with histological grade and are inversely associated with BRCA1 phosphorylation and p53 acetylation in breast cancer specimens. C23, our newly developed PP2Cδ inhibitor, promotes the anticancer effect of doxorubicin in MCF-7 xenograft–bearing nude mice. Together, our data indicate that PP2Cδ impairs p53 acetylation and DNA damage response by compromising BRCA1 function.
- Published
- 2019
21. Synthesis and properties of a lysosome-targeting fluorescent ionophore based on coumarins and squaramides
- Author
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Kun Zhang, Wen-Hua Chen, Xiao-Qiao Hong, and Xi-Hui Yu
- Subjects
Fluorophore ,010405 organic chemistry ,Organic Chemistry ,Squaramide ,Ionophore ,010402 general chemistry ,Coumarin ,01 natural sciences ,Biochemistry ,Fluorescence ,0104 chemical sciences ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Lysosome ,Biophysics ,medicine ,Physical and Theoretical Chemistry ,Derivative (chemistry) - Abstract
In this paper we present the first example of a lysosome-targeting fluorescent ionophore. Specifically, we synthesized a squaramide derivative bearing a coumarin fluorophore and a morpholinyl group, and found that it was able to target and efficiently deacidify lysosomes. In contrast, an analogue without a morpholinyl group exhibits much lower ability to localize in lysosomes and is much less active in regulating the lysosomal pH.
- Published
- 2018
22. 3-O-Carbamoyl-5,7,20-O-trimethylsilybins: Synthesis and Preliminary Antiproliferative Evaluation
- Author
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Qiao-Hong Chen, Guanglin Chen, Sitong Wu, Guangdi Wang, and Qiang Zhang
- Subjects
Pharmaceutical Science ,Silibinin ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Prostate cancer ,QD241-441 ,DU145 ,androgen receptor ,Drug Discovery ,LNCaP ,medicine ,Physical and Theoretical Chemistry ,carbamoylation ,silibinin ,Natural product ,Cell growth ,Organic Chemistry ,prostate cancer ,medicine.disease ,Androgen receptor ,cell proliferation ,chemistry ,Chemistry (miscellaneous) ,Cancer research ,Molecular Medicine ,Lead compound - Abstract
To search for novel androgen receptor (AR) modulators for the potential treatment of castration-resistant prostate cancer (CRPC), naturally occurring silibinin was sought after as a lead compound because it possesses a moderate potency towards AR-positive prostate cancer cells and its chemical scaffold is dissimilar to all currently marketed AR antagonists. On the basis of the structure–activity relationships that we have explored, this study aims to incorporate carbamoyl groups to the alcoholic hydroxyl groups of silibinin to improve its capability in selectively suppressing AR-positive prostate cancer cell proliferation together with water solubility. To this end, a feasible approach was developed to regioselectively introduce a carbamoyl group to the secondary alcoholic hydroxyl group at C-3 without causing the undesired oxidation at C2–C3, providing an avenue for achieving 3-O-carbamoyl-5,7,20-O-trimethylsilybins. The application of the synthetic method can be extended to the synthesis of 3-O-carbamoyl-3′,4′,5,7-O-tetramethyltaxifolins. The antiproliferative potency of 5,7,20-O-trimethylsilybin and its nine 3-carbamoyl derivatives were assessed in an AR-positive LNCaP prostate cancer cell line and two AR-null prostate cancer cell lines (PC-3 and DU145). Our preliminary bioassay data imply that 5,7,20-O-trimethylsilybin and four 3-O-carbamoyl-5,7,20-O-trimethylsilybins emerge as very promising lead compounds due to the fact that they can selectively suppress AR-positive LNCaP cell proliferation. The IC50 values of these five 5,7,20-O-trimethylsilybins against the LNCaP cells fall into the range of 0.11–0.83 µM, which exhibit up to 660 times greater in vitro antiproliferative potency than silibinin. Our findings suggest that carbamoylated 5,7,20-O-trimethylsilybins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.
- Published
- 2021
23. An amide mimic of desTHPdactylolide: Total synthesis and antiproliferative evaluation
- Author
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Guanglin Chen, Maricarmen Gonzalez, Guangdi Wang, Qiang Zhang, Ziran Jiang, and Qiao-Hong Chen
- Subjects
Lactams ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,01 natural sciences ,Biochemistry ,Article ,Lactones ,chemistry.chemical_compound ,Prostate cancer ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Molecular Biology ,Cell Proliferation ,Natural product ,010405 organic chemistry ,Chemistry ,Cell growth ,Organic Chemistry ,Cancer ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,0104 chemical sciences ,Androgen receptor ,010404 medicinal & biomolecular chemistry ,Cancer cell ,Lactam ,Molecular Medicine ,Bioisostere ,Drug Screening Assays, Antitumor - Abstract
(-)-Zampanolide is a unique microtubule stabilizing agent (MSA) with covalent-binding mechanism and low nanomolar anitproliferative potency towards multi-drug resistant cancer cells. MSAs have a special connection with prostate cancer by inhibiting androgen receptor nuclear translocation. Zampanolide and the structurally related dactylolide have thus been sought after by us as lead compounds for development of anti-prostate cancer agents. DesTHPdactylolide is a simplified mimic of dactylolide and has previously been synthesized by us in both configurations, with the (17R) configuration being more potent in suppressing prostate cancer cell proliferation. The current study aims to synthesize an amide mimic of (17R) desTHPdactylolide that was anticipated to be metabolically more stable than (17R) desTHPdactylolide. To this end, the amide mimic has been successfully synthesized through a 26-step transformation from 2-butyn-1-ol. Our WST-1 cell proliferation assay in five human prostate cancer cell models indicated that the lactam moiety can serve as a bioisostere for the lactone in desTHPdactylolide.
- Published
- 2021
24. Design, synthesis and evaluation of coumarin-pargyline hybrids as novel dual inhibitors of monoamine oxidases and amyloid- β aggregation for the treatment of Alzheimer's disease
- Author
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Qiao-Hong Liu, Xue-Lian Yang, Pei Cai, Jin Wang, Xiao-Bing Wang, Ling-Yi Kong, Fan Li, Hua-Li Yang, and Jia-Jia Wu
- Subjects
Male ,0301 basic medicine ,Monoamine Oxidase Inhibitors ,Amyloid β ,Cell Survival ,Synthetic membrane ,Mice, Inbred Strains ,Pharmacology ,Inhibitory postsynaptic potential ,PC12 Cells ,01 natural sciences ,Mice ,Protein Aggregates ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Alzheimer Disease ,Coumarins ,Drug Discovery ,medicine ,Animals ,Humans ,Monoamine Oxidase ,IC50 ,Amyloid beta-Peptides ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,General Medicine ,Pargyline ,Coumarin ,In vitro ,Rats ,0104 chemical sciences ,030104 developmental biology ,Monoamine neurotransmitter ,Biochemistry ,Drug Design ,medicine.drug - Abstract
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood-brain barrier. Collectively, these findings demonstrate that compound 4x was an effective and promising candidate for AD therapy.
- Published
- 2017
25. Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: Antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies
- Author
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Chengsheng Chen, Manee Patanapongpibul, Yan Dong, Xiaojie Zhang, Qiu Zhong, German Ruiz Perez, Shanchun Guo, Qiao-Hong Chen, Qiang Zhang, Guangdi Wang, Shilong Zheng, Rubing Wang, Nithya Subrahmanyam, Joshua Keith, Changde Zhang, and Guanglin Chen
- Subjects
Male ,0301 basic medicine ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Article ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,Pharmacokinetics ,Prostate ,Cell Line, Tumor ,Drug Discovery ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Potency ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,Cell growth ,Chemistry ,Cell Cycle ,Organic Chemistry ,Prostatic Neoplasms ,Epithelial Cells ,General Medicine ,medicine.disease ,Rats ,Bioavailability ,Alkadienes ,030104 developmental biology ,medicine.anatomical_structure ,Microsomes, Liver ,Curcumin ,Drug Screening Assays, Antitumor - Abstract
To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones ( 25 – 58 ) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58 , with IC 50 values in the range of 0.03–0.12 μM, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G 0 /G 1 phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone.
- Published
- 2017
26. Design, synthesis, biological evaluation and molecular docking study on peptidomimetic analogues of XK469
- Author
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Liang Yang, Ji-Feng Wu, Xun Li, Yuemao Shen, Wei Hu, Chen Li, Han Xuemei, Qiao-Hong Xia, and Zhi-Yu Li
- Subjects
Protein Conformation ,Stereochemistry ,Peptidomimetic ,Antineoplastic Agents ,Chemistry Techniques, Synthetic ,01 natural sciences ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Quinoxaline ,Quinoxalines ,Drug Discovery ,medicine ,Animals ,Humans ,Moiety ,Doxorubicin ,Neoplasm Metastasis ,Cytotoxicity ,Cell Proliferation ,Pharmacology ,010405 organic chemistry ,Organic Chemistry ,DNA ,General Medicine ,Xenograft Model Antitumor Assays ,Combinatorial chemistry ,0104 chemical sciences ,Molecular Docking Simulation ,DNA Topoisomerases, Type II ,chemistry ,Drug Design ,030220 oncology & carcinogenesis ,Kinetoplast ,Peptidomimetics ,Topoisomerase-II Inhibitor ,medicine.drug - Abstract
XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds (e.g. 13a and 13b) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert-butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA (kDNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b, 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization.
- Published
- 2016
27. Extraction, antioxidant and antibacterial activities of Broussonetia papyrifera fruits polysaccharides
- Author
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Zhong-Wei Zhang, Chunbang Ding, Liang-Qi Sun, Jing Liu, Bo Huang, Ming Yuan, Jinqiu Liao, Chao Hu, Lijun Zhou, Yang-Er Chen, Shu Yuan, Yan Huang, Zi-Li Wu, and Qiao-Hong Han
- Subjects
Arabinose ,Antioxidant ,Rhamnose ,medicine.medical_treatment ,02 engineering and technology ,Uronic acid ,Polysaccharide ,01 natural sciences ,Biochemistry ,Antioxidants ,chemistry.chemical_compound ,Structural Biology ,medicine ,Molecular Biology ,chemistry.chemical_classification ,Chromatography ,biology ,010405 organic chemistry ,Extraction (chemistry) ,General Medicine ,Broussonetia ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,chemistry ,Fruit ,0210 nano-technology ,Antibacterial activity - Abstract
Polysaccharides were extracted from Broussonetia papyrifera ((L.) L'Herit. ex Vent.) fruits (BPP), and response surface methodology was used to maximize extraction yield. The optimum extraction conditions were: ratio of water to solid, 30mL/g; extraction duration, 50min; extraction power, 180W; and extraction temperature, 60°C. Under these conditions, the yield of BPP was 8.61%. Then, BPP was purified, and three purified fractions (designated BPP-1, BPP-2 and BPP-3) were obtained for further physicochemical properties, antioxidant activity and antibacterial activity analysis. These fractions were mainly composed of glucose, mannose and arabinose residue, meanwhile, BPP-3 had a significantly higher rhamnose and uronic acid content than BPP-1 and BPP-2. And BPP-3 showed the best hydroxyl radial scavenging activity, ferric reducing activity power (FRAP), antihemolytic activity and antibacterial activity.
- Published
- 2016
28. Mosquito Acetylcholinesterase as a Target for Novel Phenyl-Substituted Carbamates
- Author
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James M. Mutunga, Joshua A. Hartsel, Max Totrov, Ming Ma, Jeffrey R. Bloomquist, Qiao-Hong Chen, Sha Ding, Dawn M. Wong, Paul R. Carlier, and Chemistry
- Subjects
0106 biological sciences ,Insecticides ,Carbamate ,Aché ,Stereochemistry ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Anopheles gambiae ,Phenylcarbamates ,Substituent ,lcsh:Medicine ,01 natural sciences ,Article ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Anopheles ,medicine ,Animals ,Humans ,Potency ,030304 developmental biology ,0303 health sciences ,biology ,lcsh:R ,Public Health, Environmental and Occupational Health ,insecticide ,toxicity ,anticholinesterase ,biology.organism_classification ,Acetylcholinesterase ,In vitro ,language.human_language ,010602 entomology ,chemistry ,Toxicity ,language ,Female ,Cholinesterase Inhibitors - Abstract
New insecticides are needed for control of disease-vectoring mosquitoes and this research evaluates the activity of new carbamate acetylcholinesterase (AChE) inhibitors. Biochemical and toxicological characterization of carbamates based on the parent structure of terbam, 3-tert-butylphenyl methylcarbamate, was performed. In vitro enzyme inhibition selectivity (Anopheles gambiae versus human) was assessed by the Ellman assay, as well as the lethality to whole insects by the World Health Organization (WHO) paper contact assay. Bromination at the phenyl C6 position increased inhibitory potency to both AChEs, whereas a 6-iodo substituent led to loss of potency, and both halogenations caused a significant reduction of mosquitocidal activity. Similarly, installation of a hexyl substituent at C6 drastically reduced inhibition of AgAChE, but showed a smaller reduction in the inhibition of hAChE. A series of 4-carboxamido analogs of the parent compound gave reduced activity against AgAChE and generally showed more activity against hAChE than AgAChE. Replacement of the 3-t-buyl group with CF3 resulted in poor anticholinesterase activity, but this compound did have measurable mosquitocidal activity. A series of methyl- and fluoro- analogs of 3-trialkylsilyl compounds were also synthesized, but unfortunately resulted in disappointing activity. Finally, a series of sulfenylated proinsecticides showed poor paper contact toxicity, but one of them had topical activity against adult female Anopheles gambiae. Overall, the analogs prepared here contributed to a better understanding of carbamate structure&ndash, activity relationships (SAR), but no new significant leads were generated.
- Published
- 2019
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29. Physicochemical properties, phenolic profiles, antioxidant capacities, and inhibitory effects on digestive enzymes of okra (Abelmoschus esculentus) fruit at different maturation stages
- Author
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Li Zhao, Li Xu, Wen Qin, Qing Zhang, Jie Zhou, Qiao-Hong Han, Ding-Tao Wu, Mo-Ting Li, Shen Dandan, Ya-Li Qin, and Shang Lin
- Subjects
chemistry.chemical_classification ,0303 health sciences ,Antioxidant ,biology ,030309 nutrition & dietetics ,Chemistry ,medicine.medical_treatment ,Flavonoid ,food and beverages ,Catechin ,04 agricultural and veterinary sciences ,biology.organism_classification ,040401 food science ,Protocatechuic acid ,03 medical and health sciences ,chemistry.chemical_compound ,Rutin ,0404 agricultural biotechnology ,Enzyme ,medicine ,Abelmoschus ,Original Article ,Food science ,Quercetin ,Food Science - Abstract
Phenolic compounds are considered the main bioactive components in okra fruits. In order to well understand the accumulation pattern of phenolic compounds in okra fruits during maturation, and to obtain okra fruits with high level of health-beneficial phenolic compounds, physicochemical properties, phenolic profiles, antioxidant capacities, and inhibitory effects on digestive enzymes of okra fruits at different maturation stages were investigated. Noticeable variations in physicochemical properties and phenolic profiles of okra were observed at different maturation stages. Phenolic compounds, including quercetin-3-O-gentiobioside, quercetin-3-O-glucoside (isoquercitrin), rutin, quercetin derivative, protocatechuic acid, and catechin derivative, were determined to be the major compounds in okra fruits, while quercetin-3-O-gentiobioside was the most abundant phenolic compound. Considering the accumulation patterns of fruit size, firmness, and total flavonoid content of okra fruits, the optimal harvest time of okra fruits with relatively high level of health-beneficial phenolic compounds was determined. Furthermore, okra fruits at different maturation stages exerted remarkable antioxidant capacities and inhibitory effects on the pancreatic lipase, α-glucosidase, and α-amylase. The Pearson’s correlation showed that quercetin-3-O-gentiobioside was one of the major contributors to the antioxidant capacities and inhibitory effects on digestive enzymes. Results are beneficial for understanding of the accumulation pattern of phenolic compounds in okra fruits during maturation, and can aid in the targeting of specific maturation stages with an optimal phenolic profile for the production of health-beneficial products.
- Published
- 2019
30. Phenolic Profiles, Antioxidant Capacities, and Inhibitory Effects on Digestive Enzymes of Different Kiwifruits
- Author
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Yu-Ling Yang, Jing-Liu He, Derong Lin, Wen Qin, Ding-Tao Wu, Hong-Yi Li, Qiao-Hong Han, Shuxiang Liu, Qin Yuan, Li Zhao, and Qing Zhang
- Subjects
Actinidia chinensis ,Antioxidant ,HPLC analysis ,medicine.medical_treatment ,Actinidia ,Phytochemicals ,Pharmaceutical Science ,phenolic compounds ,antioxidant capacity ,High-performance liquid chromatography ,Antioxidants ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Chlorogenic acid ,Dry weight ,Phenols ,lcsh:Organic chemistry ,Limit of Detection ,kiwifruit ,Drug Discovery ,medicine ,Gallic acid ,Food science ,Physical and Theoretical Chemistry ,Enzyme Inhibitors ,Procyanidin B1 ,Procyanidin B2 ,enzyme inhibition ,Chromatography, High Pressure Liquid ,biology ,Chemistry ,Plant Extracts ,Organic Chemistry ,alpha-Glucosidases ,04 agricultural and veterinary sciences ,biology.organism_classification ,040401 food science ,Chemistry (miscellaneous) ,Fruit ,Molecular Medicine - Abstract
In order to obtain high-quality kiwifruits with health-promoting characteristics, physicochemical properties, phenolic profiles, antioxidant capacities, and inhibitory effects on digestive enzymes (pancreatic lipase and &alpha, glucosidase), of fourteen different types of kiwifruit obtained from China were systematically investigated and compared. Noticeable variations in the fruits&rsquo, physicochemical properties and phenolic profiles were observed among them. The total phenolic content of Actinidia chinensis cv. Hongshi, A. chinensis cv. Jinshi, and A. chinensis cv. Jinlong were 16.52 ±, 0.26 mg GAE/g DW (dry weight), 13.38 ±, 0.20 mg GAE/g DW, and 11.02 ±, 0.05 mg GAE/g DW, respectively, which were much higher than those of the other tested kiwifruits. According to high performance liquid chromatography (HPLC) analysis, phenolic compounds, including procyanidin B1, procyanidin B2, (&minus, )-epicatechin, chlorogenic acid, gallic acid, and quercetin-3-rhamnoside, were found to be the major compounds in kiwifruits, while procyanidin B1, procyanidin B2, and chlorogenic acid were the most abundant phenolic compounds. Furthermore, all the tested kiwifruits exerted remarkable antioxidant capacities and inhibitory effects on pancreatic lipase and &alpha, glucosidase. Indeed, A. chinensis cv. Hongshi, Actinidia chinensis cv. Jinshi, and Actinidia chinensis cv. Jinlong exhibited much better antioxidant capacities and inhibitory effects on digestive enzymes than those of the other tested kiwifruits. Particularly, A. polygama showed the highest inhibitory activity on &alpha, glucosidase. Therefore, Actinidia chinensis cv. Hongshi, Actinidia chinensis cv. Jinshi, and Actinidia chinensis cv. Jinlong, as well as A. polygama could be important dietary sources of natural antioxidants and natural inhibitors against pancreatic lipase and &alpha, glucosidase, which is helpful for meeting the growing demand for high-quality kiwifruits with health-promoting characteristics in China.
- Published
- 2018
31. Synthesis and evaluation of isoprenylation-resveratrol dimer derivatives against Alzheimer's disease
- Author
-
Xue-Lian Yang, Pei Cai, Qiao-Hong Liu, Yan-Wei Tang, Cun-Jian Shi, Ling-Yi Kong, Hua-Li Yang, and Xiao-Bing Wang
- Subjects
Antioxidant ,Monoamine Oxidase Inhibitors ,DPPH ,medicine.medical_treatment ,Resveratrol ,medicine.disease_cause ,01 natural sciences ,Neuroprotection ,Antioxidants ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Alzheimer Disease ,Drug Discovery ,medicine ,Animals ,Humans ,Monoamine Oxidase ,030304 developmental biology ,Pharmacology ,Prenylation ,0303 health sciences ,ABTS ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,General Medicine ,0104 chemical sciences ,Rats ,Oxidative Stress ,Neuroprotective Agents ,Biochemistry ,Blood-Brain Barrier ,Trolox ,Monoamine oxidase B ,Dimerization ,Oxidative stress - Abstract
A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (hMAO-B). In particular, 3 and 7 showed the better inhibitory activity for hMAO-B (IC50 = 3.91 ± 0.23 μM, 0.90 ± 0.01 μM) respectively. Compound 3 (IC50 = 46.95 ± 0.21 μM for DPPH, 1.43 and 1.74 trolox equivalent by ABTS and FRAP method respectively), and 7 (IC50 = 35.33 ± 0.15 μM for DPPH, 1.70 and 1.97 trolox equivalent by ABTS method and FRAP method respectively) have excellent antioxidant effects. Cellular assay shown that 3 and 7 had lower toxicity and were resistant to neurotoxicity induced by oxidative toxins (H2O2, rotenone and oligomycin-A). More importantly, the selected compounds have neuroprotective effects against ROS generation, H2O2-induced apoptosis and a significant in vitro anti-inflammatory activity. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that 3 and 7 would be predominant to cross the blood-brain barrier. In this study, mouse microglia BV2 cells were used to establish cell oxidative stress injury model with H2O2 and to explore the protective effect and mechanism of 3 and 7. In general, 3 and 7 can be considered candidates for potential treatment of AD.
- Published
- 2018
32. Synthesis and biological effect of lysosome-targeting fluorescent anion transporters with enhanced anionophoric activity
- Author
-
Wen-Hua Chen, Kin Yip Tam, Xiang-Yu He, and Xiao-Qiao Hong
- Subjects
Morpholines ,Clinical Biochemistry ,Substituent ,Pharmaceutical Science ,01 natural sciences ,Biochemistry ,Chloride ,Cathepsin B ,chemistry.chemical_compound ,Chlorides ,Coumarins ,Lysosome ,Drug Discovery ,medicine ,Humans ,Molecular Biology ,chemistry.chemical_classification ,Ion Transport ,Trifluoromethyl ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Transporter ,Hydrogen-Ion Concentration ,Fluorescence ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,medicine.anatomical_structure ,Enzyme ,Molecular Medicine ,Lysosomes ,Cyclobutanes ,HeLa Cells ,medicine.drug - Abstract
Two lysosome-targeting fluorescent anion transporters derived from coumarins, trifluoromethylated arylsquaramides and morpholines were synthesized, and their specificity and efficiency to target and alkalize lysosomes were investigated. They are able to target lysosomes specifically. Compared with the previous analogue without trifluoromethyl substituents, these two conjugates, in particular the one having a 3,5-bis(trifluoromethyl) substituent, exhibit significantly higher ability to facilitate the transport of chloride anions, alkalize lysosomes and reduce the activity of lysosomal Cathepsin B enzyme. The present finding suggests that improving the anionophoric activity of lysosome-targeting fluorescent anion transporters is favorable to the efficiency to alkalize lysosomes and deactivate lysosomal Cathepsin B enzyme.
- Published
- 2020
33. 3- O -Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells
- Author
-
Sheng Zhang, Guanglin Chen, Michael Huang, Guangdi Wang, Xiaojie Zhang, Shilong Zheng, Qiang Zhang, Qiao-Hong Chen, Bao Vue, and Timmy Lee
- Subjects
Male ,0301 basic medicine ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Silibinin ,Antineoplastic Agents ,Apoptosis ,Alkylation ,Biochemistry ,Article ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Drug Discovery ,LNCaP ,Humans ,Structure–activity relationship ,Molecular Biology ,Alkyl ,Cell Proliferation ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,Cell growth ,Chemistry ,Organic Chemistry ,Prostatic Neoplasms ,Cell Cycle Checkpoints ,Cell cycle ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Silymarin - Abstract
Eight 3-O-alkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin through two synthetic approaches. A one-pot reaction, starting with aerobic oxidation of silibinin followed by direct alkylation of the phenolic hydroxyl group in the subsequent 2,3-dehydrosilibinin, furnishes the desired derivatives in 11–16% yields. The three-step procedure employing benzyl ether to protect 7-OH in silibinin generates the desired derivatives in 30–46% overall yields. The antiproliferative activity of the 2,3-dehydrosilibinin derivatives against both androgen-sensitive and androgen-insensitive prostate cancer cells have been assessed using a WST-1 cell proliferation assay. All derivatives exhibited greater antiproliferative potency than silibinin, with 2,3-dehydrosilibinins each possessing a three- to five-carbon linear alkyl group to 3-OH (IC50 values in a range of 1.71 to 3.06 μM against PC-3 and LNCaP cells) as the optimal derivatives. The optimal potency was reached with three- to five-carbon alkyl groups. Our findings suggest that 3-O-propyl-2,3-dehydrosilibinin effectively inhibits the growth of PC-3 prostate cancer cells by arresting cell cycle in the G0/G1 phase, but not by activating PC-3 cell apoptosis.
- Published
- 2016
34. Synthesis and evaluation of 1,7-diheteroarylhepta-1,4,6-trien-3-ones as curcumin-based anticancer agents
- Author
-
Rubing Wang, Guanglin Chen, Qiao-Hong Chen, Qiang Zhang, Shilong Zheng, Guangdi Wang, Xiaojie Zhang, Chengsheng Chen, and Qiu Zhong
- Subjects
Male ,Curcumin ,Cell cycle checkpoint ,Uterine Cervical Neoplasms ,Antineoplastic Agents ,Pharmacology ,Trientine ,01 natural sciences ,Article ,HeLa ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Humans ,Structure–activity relationship ,Cytotoxicity ,Cell Proliferation ,biology ,010405 organic chemistry ,Cell growth ,Organic Chemistry ,Prostatic Neoplasms ,General Medicine ,medicine.disease ,biology.organism_classification ,0104 chemical sciences ,chemistry ,Apoptosis ,Drug Design ,030220 oncology & carcinogenesis ,Female ,Drug Screening Assays, Antitumor ,HeLa Cells - Abstract
Thirty (1E,4E,6E)-1,7-diaryl-1,4,6-heptatrien-3-ones, featuring a central linear trienone linker and two identical nitrogen-containing heteroaromatic rings, were designed and synthesized as curcumin-based anticancer agents on the basis of their structural similarity to the enol-tautomer of curcumin, in addition to taking advantage of the possibly enhanced pharmacokinetic profiles contributed by the basic nitrogen-containing heteroaromatic rings. Their cytotoxicity and antiproliferative activity were evaluated towards both androgen-dependent and androgen-independent prostate cancer cell lines, as well as HeLa human cervical cancer cells. Among them, the ten most potent analogues are 5- to 36-fold more potent than curcumin in inhibiting cancer cell proliferation. The acquired structure-activity relationship data indicate (i) that (1E,4E,6E)-1,7-diaryl-1,4,6-heptatrien-3-ones represent a potential scaffold for development of curcumin-based agents with substantially improved cytotoxicity and anti-proliferative effect; and (ii) 1-alkyl-1H-imidazol-2-yl and 1-alkyl-1H-benzo[d]imidazole-2-yl serve as optimal heteroaromatic rings for increased in vitro potency of this scaffold. Two of most potent compounds displayed no apparent cytotoxicity toward MCF-10A normal mammary epithelial cells at 1 μM concentration. Treatment of PC-3 prostate cancer cells with the most potent compound led to appreciable cell cycle arrest at a G1/G0 phase and cell apoptosis induction.
- Published
- 2016
35. Silibinin derivatives as anti-prostate cancer agents: Synthesis and cell-based evaluations
- Author
-
Konstantinos Parisis, Xiaojie Zhang, Sheng Zhang, Shilong Zheng, Qiang Zhang, Qiao-Hong Chen, Bao Vue, and Guangdi Wang
- Subjects
Male ,0301 basic medicine ,Silibinin ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Article ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Drug Discovery ,LNCaP ,medicine ,Humans ,Structure–activity relationship ,Potency ,Cell Proliferation ,Cell growth ,Chemistry ,Cell Cycle ,Organic Chemistry ,G1 Phase ,Prostate ,Prostatic Neoplasms ,Cancer ,General Medicine ,Cell cycle ,medicine.disease ,030104 developmental biology ,Silybin ,030220 oncology & carcinogenesis ,Silymarin - Abstract
This study aims to systematically explore the alkylation effect of 7-OH in silibinin and 2,3-dehydrosilibinin on the antiproliferative potency toward three prostate cancer cell lines. Eight 7-O-alkylsilibinins, eight 7-O-alkyl-2,3-dehydrosilibinins, and eight 3,7-O-dialkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin for the in vitro cell-based evaluation. The WST-1 cell proliferation assay indicates that nineteen out of twenty-four silibinin derivatives have significantly improved antiproliferative potency when compared with silibinin. 7-O-Methylsilibinin (2) and 7-O-ethylsilibinin (3) have been identified as the most potent compounds with 98- and 123-fold enhanced potency against LNCaP human androgen-dependent prostate cancer cell line. Among 2,3-dehydrosilibinin derivatives, 7-O-methyl-2,3-dehydrosilibinin (10) and 7-O-ethyl-2,3-dehydrosilibinin (11) have been identified as the optimal compounds with the highest potency towards both androgen-dependent LNCaP and androgen-independent PC-3 prostate cancer cell lines. 7-O-Ethyl-2,3-dehydrosilibinin (11) was demonstrated to arrest PC-3 cell cycle at the G0/G1 phase and to induce PC-3 cell apoptosis. The findings in this study suggest that antiproliferative potency of silibinin and 2,3-dehydrosilibinin can be appreciably enhanced through suitable chemical modifications on the phenolic hydroxyl group at C-7 and that introduction of a chemical moiety with the potential to improve bioavailability through a linker to 7-OH in silibinin and 2,3-dehydrosilibinin would be a feasible strategy for the development of silibinin derivatives as anti-prostate cancer agents.
- Published
- 2016
36. A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation
- Author
-
Rubing Wang, Liva Harinantenaina Rakotondraibe, Qiao-Hong Chen, Andrew Hoover, Guanglin Chen, Kevin Yu, Francisco Leon, Xiaojie Zhang, Ermias Addo Mekuria, and Nithya Subrahmanyam
- Subjects
Curcumin ,Clinical Biochemistry ,Pharmaceutical Science ,Genistein ,Antineoplastic Agents ,Pharmacology ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Structure–activity relationship ,Molecular Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Drug Synergism ,chemistry ,Drug Design ,Chromone ,Cancer cell ,Molecular Medicine ,Bioisostere ,Drug Screening Assays, Antitumor ,Pharmacophore ,Linker - Abstract
Inspired by the synergistic effects of dietary natural products with different scaffolds on the inhibition of cancer cell proliferation, incorporation of central (1E,4E)-1,4-penta-dien-3-one linker (an optimal substitute for the central metabolically unstable diketone linker of curcumin), 1-alkyl-1H-imidazol-2-yl (a promising bioisostere of terminal aryl group in curcumin), and chromone (the common pharmacophore in genistein and quercetin) into one chemical entity resulted in ten new hybrid molecules, 3-((1E,4E)-5-(1-alkyl-1H-imidazol-2-yl)-3-oxopenta-1,4-dien-1-yl)-4H-chromen-4-ones. They were synthesized through a three-step transformation using acid-catalyzed aldol condensation as key step. The WST-1 cell proliferation assay showed that they have greater anti-proliferative potency than curcumin, quercetin, and genistein on both androgen-dependent and androgen-independent human prostate cancer cells.
- Published
- 2015
37. X-ray powder diffraction data for ertapenem side chain, C20H19N3O7S
- Author
-
Xiang Lin, Qiao Hong Du, Xi Lin Peng, Hui Li, and Wei Ling Zhuo
- Subjects
Radiation ,Materials science ,X-ray ,Condensed Matter Physics ,Space (mathematics) ,chemistry.chemical_compound ,Crystallography ,Volume (thermodynamics) ,chemistry ,Impurity ,Group (periodic table) ,Side chain ,General Materials Science ,Instrumentation ,Ertapenem ,Powder diffraction - Abstract
X-ray powder diffraction data, unit-cell parameters, and space group for ertapenem side chain, C20H19N3O7S, are reported [a = 4.907(6) Å, b = 18.686(3) Å, c = 22.071(1) Å, α = γ = 90°, β = 90.759(5)°, unit-cell volume V = 2023.82 Å3, Z = 4, ρcal = 1.462 g cm−3, and space group P21/c]. All measured lines were indexed and are consistent with the P21/c space group. No detectable impurity was observed.
- Published
- 2017
38. Second-Generation Androgen Receptor Antagonists as Hormonal Therapeutics for Three Forms of Prostate Cancer
- Author
-
Nicholas Olveda, Alyssa Rivera, Kevin Muthima, Hubert Muchalski, Pravien Rajaram, and Qiao-Hong Chen
- Subjects
Male ,Oncology ,Pharmaceutical Science ,Review ,Analytical Chemistry ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,androgen receptor ,Drug Discovery ,Medicine ,Androgen Receptor Antagonists ,apalutamide ,0303 health sciences ,enzalutamide ,Drug discovery ,darolutamide ,Apalutamide ,prostate cancer ,Prostatic Neoplasms, Castration-Resistant ,Darolutamide ,Thiohydantoins ,Receptors, Androgen ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Benzamides ,Molecular Medicine ,Signal Transduction ,medicine.medical_specialty ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Internal medicine ,Nitriles ,Phenylthiohydantoin ,Humans ,Enzalutamide ,Physical and Theoretical Chemistry ,030304 developmental biology ,business.industry ,Organic Chemistry ,Prostatic Neoplasms ,medicine.disease ,Androgen receptor ,chemistry ,Drug Resistance, Neoplasm ,Pyrazoles ,business ,Hormone - Abstract
Enzalutamide is the first second-generation nonsteroidal androgen receptor (AR) antagonist with a strong binding affinity to AR. Most significantly, enzalutamide can prolong not only overall survival time and metastatic free survival time for patients with lethal castration-resistant prostate cancer (CRPC), but also castration-resistant free survival time for patients with castration-sensitive prostate cancer (CSPC). Enzalutamide has thus been approved by the US Food and Drug Administration (FDA) for the treatment of both metastatic (in 2012) and non-metastatic (in 2018) CRPC, as well as CSPC (2019). This is an inspiring drug discovery story created by an amazing interdisciplinary collaboration. Equally important, the successful clinical use of enzalutamide proves the notion that the second-generation AR antagonists can serve as hormonal therapeutics for three forms of advanced prostate cancer. This has been further verified by the recent FDA approval of the other two second-generation AR antagonists, apalutamide and darolutamide, for the treatment of prostate cancer. This review focuses on the rational design and discovery of these three second-generation AR antagonists, and then highlights their syntheses, clinical studies, and use. Strategies to overcome the resistance to the second-generation AR antagonists are also reviewed.
- Published
- 2020
39. 23-O-Substituted-2,3-Dehydrosilybins Selectively Suppress Androgen Receptor-Positive LNCaP Prostate Cancer Cell Proliferation
- Author
-
Ziran Jiang, Guanglin Chen, Yogeshwari Oka, Nagat Alrubati, Qiao-Hong Chen, Alexia Orozco, Qiang Zhang, Jasleen Kaur, Arman Sekhon, and Guangdi Wang
- Subjects
Pharmacology ,0303 health sciences ,Natural product ,Antiandrogens ,Androgen Receptor Positive ,Silibinin ,Plant Science ,General Medicine ,medicine.disease ,Androgen receptor ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Complementary and alternative medicine ,chemistry ,030220 oncology & carcinogenesis ,Drug Discovery ,LNCaP ,Cancer research ,medicine ,Flavonolignan ,030304 developmental biology - Abstract
As part of our ongoing project to search for natural product-based antiandrogens, nine derivatives of 2,3-dehydrosilybin have been synthesized for the evaluation of its antiproliferative activity in an androgen receptor-positive prostate cancer cell model. Specifically, 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin was synthesized through two approaches, and eight 23- O-substituted-3,5,7,20- O-tetramethyl-2,3-dehydrosilybins were achieved from 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin. The antiproliferative potency of 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and its eight derivatives were assessed in an androgen receptor (AR)-positive LNCaP prostate cancer cell line, as well as in two AR-negative (PC-3 and DU145) prostate cancer cell models as a comparison. Our WST cell proliferation assay data indicate 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and most of its 23- O-substituents can selectively inhibit AR-positive LNCaP prostate cancer cell proliferation. Our data suggest that 3,5,7,20- O-tetramethyl-2,3-dehydrosilibins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.
- Published
- 2020
40. Optimization of diarylpentadienones as chemotherapeutics for prostate cancer
- Author
-
Manee Patanapongpibul, Qiao-Hong Chen, Guangdi Wang, Qiang Zhang, Guanglin Chen, Shanchun Guo, Shilong Zheng, and Changde Zhang
- Subjects
0301 basic medicine ,Ullmann condensation ,Male ,Curcumin ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Pharmacology ,Biochemistry ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,Structure-Activity Relationship ,0302 clinical medicine ,Drug Stability ,In vivo ,Cell Line, Tumor ,Drug Discovery ,medicine ,Potency ,Animals ,Humans ,Molecular Biology ,Cell Proliferation ,Organic Chemistry ,Prostatic Neoplasms ,Stereoisomerism ,medicine.disease ,Bioavailability ,Formylation ,Rats ,Alkadienes ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Drug Design ,Cancer cell ,Microsomes, Liver ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Half-Life - Abstract
Our earlier studies indicate that (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yl)penta-1,4-diene-3-ones and (1E,4E)-1,5-bis(1-alkyl-1H-benzo[d] imidazol-2-yl)penta-1,4-diene-3-ones exhibit up to 121-fold greater antiproliferative potency than curcumin in human prostate cancer cell models, but only 2–10 fold increase in mouse plasma concentrations. The present study aims to further optimize them as anti-prostate cancer agents with both good potency and bioavailability. (1E,4E)-1,5-Bis(1H-imidazol-2-yl)penta-1,4-diene-3-one, the potential metabolic product of (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yl)penta-1,4-diene-3-ones, was synthesized and evaluated for its anti-proliferative activity. The promising potency of 1,5-bis(1-alkyl-1H-imidazol-2-yl)penta-1,4-diene-3-ones was completely abolished by removing the 1-alkyl group, suggesting the critical role of an appropriate group on the N1 position. We then envisioned that N-aryl substitution to exclude the C-H bond on the carbon adjacent to the N1 position (α-H) may increase the metabolic stability. Consequently, seven (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yl)penta-1,4-dien-3-ones and three (1E,4E)-1,5-bis(1-aryl-1H-benzo[d]imidazol-2-yl)penta-1,4-dien-3-ones, as well as three (1E,4E)-1,5-bis(1-aryl-1H-pyrrolo[3,2-b]pyridine-2-yl)penta-1,4-dien-3-ones, were synthesized through a three-step transformation, including N-arylation via Ullmann condensation, formylation, and Horner-Wadsworth-Emmons reaction. Six optimal (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yl)penta-1,4-dien-3-ones exhibit 24- to 375-fold improved potency as compared with curcumin. Replacement of the imidazole with bulkier benzoimidazole and 4-azaindole results in a substantial decrease in the potency. (1E,4E)-1,5-Bis(1-(2-methoxyphenyl)-1H-imidazol-2-yl)penta-1,4-dien-3-one (17d) was established as an optimal compound with both superior potency and good bioavailability that is sufficient to provide the therapeutic efficacy necessary to suppress in vivo tumor growth.
- Published
- 2018
41. Optimized synthesis and antiproliferative activity of desTHPdactylolides
- Author
-
Rubing Wang, Guangdi Wang, Qiang Zhang, Bao Vue, Shilong Zheng, Guanglin Chen, Qiao-Hong Chen, Manee Patanapongpibul, and James D. White
- Subjects
Zampanolide ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Docetaxel ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,chemistry.chemical_compound ,Lactones ,DU145 ,Cell Line, Tumor ,Drug Discovery ,Humans ,Molecular Biology ,Cell Proliferation ,010405 organic chemistry ,Cell growth ,Allyl iodide ,Organic Chemistry ,Stereoisomerism ,Bridged Bicyclo Compounds, Heterocyclic ,Combinatorial chemistry ,0104 chemical sciences ,Williamson ether synthesis ,chemistry ,Drug Resistance, Neoplasm ,Yield (chemistry) ,Molecular Medicine ,Taxoids ,Enantiomer ,Lead compound - Abstract
Dactylolide and certain analogues are attractive targets for study due to their structural resemblance to zampanolide, a very promising anticancer lead compound and a unique covalent-binding microtubule stabilizing agent. The primary goal of this project is identification and synthesis of simplified analogues of dactylolide that would be easier to prepare and could be investigated for antiproliferative activity in comparison with zampanolide. Extension of Almann's concept of a simplified zampanolide analogue to dactylolide in the form of desTHPdactylolide was attractive not only for reasons of synthetic simplification but also for the prospect that analogues of dactylolide could be prepared in both (17S) and (17R) configurations. Since Altmann's overall yield for the six-step procedure leading to the C9-C18 fragment of desTHPdactylolide was only 8.7%, a study focused on optimized synthesis and antiproliferative evaluation of each enantiomer of desTHPdactylolide was initiated using Altmann's route as a framework. To this end, two optimized approaches to this fragment C9-C18 were successfully developed by us using allyl iodide or allyl tosylate as the starting material for a critical Williamson ether synthesis. Both (17S) and (17R) desTHPdactylolides were readily synthesized in our laboratory using optimized methods in yields of 37-43%. Antiproliferative activity of the pair of enantiomeric desTHPdactylolides, together with their analogues, was evaluated in three docetaxel-sensitive and two docetaxel-resistant prostate cancer cell models using a WST-1 cell proliferation assay. Surprisingly, (17R) desTHPdactylolide was identified as the eutomer in the prostate cancer cell models. It was found that (17S) and (17R) desTHPdactylolide exhibit equivalent antiproliferative potency towards both docetaxel-sensitive (PC-3 and DU145) and docetaxel-resistant prostate cancer cell lines (PC-3/DTX and DU145/DTX).
- Published
- 2018
42. Novel 8-hydroxyquinoline derivatives targeting β-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease
- Author
-
Ling-Yi Kong, Pei Cai, Xue-Lian Yang, Yong Yin, Qiao-Hong Liu, Xiao-Bing Wang, and Jia-Jia Wu
- Subjects
0301 basic medicine ,Male ,Antioxidant ,Oxygen radical absorbance capacity ,Cell Survival ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,medicine.disease_cause ,Biochemistry ,Neuroprotection ,PC12 Cells ,Antioxidants ,Permeability ,03 medical and health sciences ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,0302 clinical medicine ,In vivo ,Alzheimer Disease ,Drug Discovery ,medicine ,Animals ,Chelation ,Molecular Biology ,Chelating Agents ,Amyloid beta-Peptides ,Organic Chemistry ,Body Weight ,Neurotoxicity ,medicine.disease ,Oxyquinoline ,Rats ,Oxidative Stress ,030104 developmental biology ,chemistry ,Blood-Brain Barrier ,Metals ,Drug Design ,Molecular Medicine ,Trolox ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer’s disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced Aβ1−42 aggregation and potential antioxidant properties especially compound 5b (IC50 = 5.64 μM for self-induced Aβ aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu2+/Zn2+-induced Aβ1−42 aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H2O2 and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood–brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo. Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy.
- Published
- 2018
43. Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption
- Author
-
Chen-he Zhou, Jia-hong Meng, Yu-te Yang, Bin Hu, Jian-qiao Hong, Zheng-tao Lv, Kun Chen, Boon Chin Heng, Guang-yao Jiang, Jian Zhu, Zhao-hui Cheng, Wei Zhang, Le Cao, Wei Wang, Wei-liang Shen, Shi-gui Yan, and Hao-bo Wu
- Subjects
0301 basic medicine ,Agonist ,medicine.drug_class ,Osteoporosis ,Bone resorption ,03 medical and health sciences ,chemistry.chemical_compound ,Osteoclast ,cepharanthine ,medicine ,Cepharanthine ,Pharmacology (medical) ,Protein kinase B ,Anisomycin ,Original Research ,Pharmacology ,biology ,Akt ,lcsh:RM1-950 ,medicine.disease ,osteoporosis ,030104 developmental biology ,medicine.anatomical_structure ,osteoclasts ,lcsh:Therapeutics. Pharmacology ,chemistry ,RANKL ,Cancer research ,biology.protein ,JNK - Abstract
Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata) exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist) and/or SC79 (an AKT agonist) in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.
- Published
- 2018
44. Design, Synthesis, and Evaluation of Genistein Analogues as Anti-Cancer Agents
- Author
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Francisco Leon, Qiang Zhang, Guangdi Wang, Shilong Zheng, Qiao-Hong Chen, Xiaojie Zhang, Rubing Wang, Eduardo DeLa Torre, and Pahoua Xiong
- Subjects
Male ,Spectrometry, Mass, Electrospray Ionization ,Cancer Research ,Magnetic Resonance Spectroscopy ,Cell ,Uterine Cervical Neoplasms ,Genistein ,Antineoplastic Agents ,Pharmacology ,Article ,HeLa ,Prostate cancer ,chemistry.chemical_compound ,Cell Line, Tumor ,LNCaP ,medicine ,Humans ,Cytotoxicity ,Cell Proliferation ,biology ,Cell growth ,Prostatic Neoplasms ,food and beverages ,Cancer ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,chemistry ,Drug Design ,Molecular Medicine ,Female - Abstract
Genistein is a bioactive isoflavone derived from soybeans. The tie-in between the intake of genistein and the decreased incidence of some solid tumors (including prostate cancer) has been demonstrated by epidemiological studies. The potential of genistein in treating prostate cancer has also been displayed by in vitro cell-based and in vivo animal experiments. Genistein has entered clinical trials for both chemoprevention and potential treatment of prostate cancer. Even though the low oral bioavailability has presented the major challenges to genistein’s further clinical development, chemical modulation of genistein holds the promise to generate potential anti-prostate cancer agents with enhanced potency and/or better pharmacokinetic profiles than genistein. As part of our ongoing project to develop natural products-based anti-prostate cancer agents, the current study was undertaken to synthesize eight genistein analogues for cytotoxic evaluation in three prostate cancer cell lines (PC-3, DU-145, LNCaP; both androgen-sensitive and androgen-refractory cell lines), as well as one aggressive cervical cancer cell line (HeLa). Eight genistein analogues have been successfully synthesized with Suzuki-Miyaura coupling reaction as a key step. Their in vitro anti-cancer potential was evaluated by trypan blue exclusion assay and WST-1 cell proliferation assay against a panel of four human cancer cell lines. The acquired data suggest i) that the C-5 and C-7 hydroxyl groups in genistein are very important for the cytotoxicity and anti-proliferative activity; and ii) that 1-alkyl-1H-pyrazol-4-yl and pyridine-3-yl might act as good bioisosteres for the 4'-hydroxyphenyl moiety in genistein.
- Published
- 2015
45. Fabrication of BPPO Isoporous Membranes for Water Treatment
- Author
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Bing Yu, Hua Yuan, Hai Lin Cong, Ming Chi, Yong Li Luo, and Qiao Hong Peng
- Subjects
Materials science ,Chromatography ,Microfiltration ,General Engineering ,Oxide ,Permeation ,chemistry.chemical_compound ,Membrane ,Chemical engineering ,chemistry ,Phenylene ,Water treatment ,Self-assembly ,Biosensor - Abstract
A isoporous brominated poly (phenylene oxide) (BPPO) microfiltration membrane system, fabricated by figure breath method, was demonstrated for the effective removal of impurity from contaminated water. The water permeation flux of BPPO membrane is higher. Such ordered isoporous membranes can also be applied in other size-based separation systems, enabling new opportunities in bioseparation and biosensors.
- Published
- 2015
46. The Synthesis and Property of Neutral Silicone Glass Sealant
- Author
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Hua Yuan, Hai Lin Cong, Xiao Hui Gao, Xin Chen, Xiaodan Xu, Shu Jing Yang, Bing Yu, Qiao Hong Peng, and Rui Xia Yang
- Subjects
Silica nanoparticles ,chemistry.chemical_compound ,Materials science ,Silicone ,chemistry ,Sealant ,General Engineering ,Plasticizer ,Composite material - Abstract
The neutral silicone glass sealant was prepared and the mechanical performance of this silicone glass sealant was researched in this paper. The recipe of neutral silicone glass sealant was studied. Besides, the influence of different cross-linking agents was researched; meanwhile, the effect of plasticizer and reinforcing agent on the mechanical properties of the material was studied. To obtain the best properties of neutral silicone glass sealant, the recipe should be taken further efforts to optimize.
- Published
- 2015
47. Structure–Activity Relationship and Pharmacokinetic Studies of 1,5-Diheteroarylpenta-1,4-dien-3-ones: A Class of Promising Curcumin-Based Anticancer Agents
- Author
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Xiaojie Zhang, Changde Zhang, Chengsheng Chen, Qiao-Hong Chen, Qiang Zhang, Rubing Wang, Qiu Zhong, Guanglin Chen, Guangdi Wang, and Shilong Zheng
- Subjects
Male ,Models, Molecular ,Curcumin ,Stereochemistry ,Uterine Cervical Neoplasms ,Antineoplastic Agents ,Article ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,Prostate ,Pentanones ,Drug Discovery ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Potency ,Structure–activity relationship ,Tissue Distribution ,Cytotoxicity ,Chromatography, High Pressure Liquid ,Cell Proliferation ,Trifluoromethyl ,Molecular Structure ,Chemistry ,Prostatic Neoplasms ,In vitro ,Mice, Inbred C57BL ,Thiazoles ,medicine.anatomical_structure ,Drug Design ,Molecular Medicine ,Female ,Linker - Abstract
Forty-three 1,5-diheteroaryl-1,4-pentadien-3-ones were designed as potential curcumin mimics, structurally featuring a central five-carbon dienone linker and two identical nitrogen-containing aromatic rings. They were synthesized using a Horner–Wadsworth–Emmons reaction as the critical step and evaluated for their cytotoxicity and antiproliferative activities toward both androgen-insensitive and androgen-sensitive prostate cancer cell lines and an aggressive cervical cancer cell line. Most of the synthesized compounds showed distinctly better in vitro potency than curcumin in the four cancer cell lines. The structure–activity data acquired from the study validated (1E,4E)-1,5-dihereroaryl-1,4-pentadien-3-ones as an excellent scaffold for in-depth development for clinical treatment of prostate and cervical cancers. 1-Alkyl-1H-imidazol-2-yl, ortho pyridyl, 1-alkyl-1H-benzo[d]imidazole-2-yl, 4-bromo-1-methyl-1H-pyrazol-3-yl, thiazol-2-yl, and 2-methyl-4-(trifluoromethyl)thiazol-5-yl were identified as optimal heteroaromatic rings for the promising in vitro potency. (1E,4E)-1,5-Bis(2-methyl-4-(trifluoromethyl)thiazol-5-yl)penta-1,4-dien-3-one, featuring thiazole rings and trifluoromethyl groups, was established as the optimal lead compound because of its good in vitro potency and attractive in vivo pharmacokinetic profiles.
- Published
- 2015
48. Curcumin-Based Anti-Prostate Cancer Agents
- Author
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Qiao-Hong Chen
- Subjects
Male ,Drug ,Cancer Research ,Curcumin ,media_common.quotation_subject ,Biological Availability ,Antineoplastic Agents ,Pharmacology ,Structure-Activity Relationship ,chemistry.chemical_compound ,Prostate cancer ,Pharmacokinetics ,Animals ,Humans ,Medicine ,media_common ,business.industry ,Prostatic Neoplasms ,Cancer ,medicine.disease ,Bioavailability ,Solubility ,chemistry ,Drug development ,Docetaxel ,Cancer research ,Molecular Medicine ,business ,medicine.drug - Abstract
Prostate cancer possesses the highest occurrence rate and is the second-paramount disease that causes cancer-affiliated death among men in the United States. Approximately 30,000 men die each year of castration-resistant prostate cancer due to the inevitable progression of resistance to first-line treatment with docetaxel. The safety profile of dietary curcumin in humans has been well-documented, and its therapeutic prospect in treating prostate cancer, especially for castration-resistant prostate cancer, has been evidenced in several cell culture systems and human xenograft mouse models. The critical disadvantage of curcumin as a drug candidate is its low bioavailability caused by poor water solubility and rapid in vivo metabolism. Curcumin is characteristic of regulating multiple targets, representing a good example for the philosophy to search for multitargeted drugs in the realm of drug design and drug development. This feature, together with its potential in treating castration-resistant prostate cancer and its safety profile, enables curcumin to serve as an ideal lead compound for the design and syntheses of curcumin-based agents with improved potential for the clinical therapies of prostate cancer. Several researches aiming to improve its bioavailability and potency resulted in the discovery and development of a wealth of curcumin-based compounds with an enhanced anticancer potential and/or an improved pharmacokinetic profile. This review starts with a brief summarization of the prospect of curcumin in treating prostate cancer and its mechanisms of action, then provides an in-depth overview of current development of curcumin-based anti-prostate cancer agents and their structure-activity relationships, and ends with the syntheses and pharmacokinetic studies of curcumin.
- Published
- 2015
49. Rational Design and Multibiological Profiling of Novel Donepezil-Trolox Hybrids against Alzheimer's Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties
- Author
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Qiao-Hong Liu, Ling-Yi Kong, Si-Qiang Fang, Xue-Lian Yang, Hao Hong, Jia-Jia Wu, Pei Cai, and Xiao-Bing Wang
- Subjects
0301 basic medicine ,Male ,Antioxidant ,Physiology ,DPPH ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,Biochemistry ,PC12 Cells ,Antioxidants ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Donepezil ,Chelating Agents ,Mice, Inbred ICR ,ABTS ,General Medicine ,Oxidants ,Acetylcholinesterase ,Molecular Docking Simulation ,Blood-Brain Barrier ,Indans ,Monoamine oxidase B ,Microglia ,medicine.drug ,Monoamine Oxidase Inhibitors ,Cognitive Neuroscience ,Neurotoxins ,Protein Aggregation, Pathological ,Cell Line ,03 medical and health sciences ,Structure-Activity Relationship ,Alzheimer Disease ,medicine ,Animals ,Humans ,Chromans ,Amyloid beta-Peptides ,Neurotoxicity ,Cell Biology ,medicine.disease ,Peptide Fragments ,Rats ,030104 developmental biology ,chemistry ,Drug Design ,Trolox ,Cholinesterase Inhibitors ,030217 neurology & neurosurgery ,Copper ,Central Nervous System Agents - Abstract
A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer’s disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41.33 μM IC50 by DPPH method, 1.72 and 1.79 trolox equivalent by ABTS and ORAC methods), excellent copper chelation, and Aβ1–42 aggregation inhibition effect. Furthermore, cellular tests indicated that 6d has very low toxicity and is capable of combating oxidative toxin (H2O2, rotenone, and oligomycin-A) induced neurotoxicity. Most importantly, oral administration of 6d demonstrated notable improvements on cognition and spatial memory against scopolamine-induced acute memory deficit as well as ...
- Published
- 2017
50. Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease
- Author
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Xue-Lian Yang, Qiao-Hong Liu, Xiao-Bing Wang, Si-Qiang Fang, Yan-Wei Tang, Ling-Yi Kong, Pei Cai, Hua-Li Yang, and Cheng Wang
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Antioxidant ,Monoamine Oxidase Inhibitors ,DPPH ,Cell Survival ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Ligands ,01 natural sciences ,Biochemistry ,Neuroprotection ,PC12 Cells ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Protein Aggregates ,Structure-Activity Relationship ,Alzheimer Disease ,Drug Discovery ,medicine ,Animals ,Humans ,Molecular Biology ,IC50 ,Monoamine Oxidase ,ABTS ,Amyloid beta-Peptides ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,Biological activity ,Hydrogen Peroxide ,Peptide Fragments ,Salicylates ,0104 chemical sciences ,Rats ,Molecular Docking Simulation ,030104 developmental biology ,chemistry ,Drug Design ,Molecular Medicine ,Trolox ,Monoamine oxidase B ,Imines ,Microglia - Abstract
A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-β (Aβ) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aβ1-42 aggregation (91.3±2.1%, 25μM), inhibition of hMAO-B (IC50, 1.73±0.39μM), antioxidant effects (43.4±2.6μM of IC50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H2O2-induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs.
- Published
- 2017
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