87 results on '"Qiao, Hong"'
Search Results
2. Determination of Trans-loxoprofen-alcohol Tromethamine in Pregnant SD Rats by a Validated LC-MS/MS Method:Application to a Toxicokinetics and Tissue Distribution Study
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Xu Lingling, Shao Qing, Yuan Yanjuan, Qiao Hong-qun, and Zhou Wenjun
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Chromatography ,Tromethamine ,Chemistry ,Lc ms ms ,Biophysics ,Pharmaceutical Science ,Molecular Medicine ,Toxicokinetics ,Tissue distribution ,Biochemistry ,Loxoprofen alcohol - Abstract
Background: As an anti-inflammatory prodrug, loxoprofen is metabolized into transloprofenol to treat diseases related to pain and inflammation. Although loxoprofen has fewer adverse effects than other NSAIDs, the safety of its usage during pregnancy remains unclear and needs to be considered. Fortunately, the toxicokinetics and tissue distribution study of transloxoprofen- alcohol in pregnant rats can resolve the problem. Objective: The purpose of this study is to establish a simple, sensitive, and effective LC-MS/MS analysis method for determining the concentration of trans-loxoprofen alcohol in plasma and tissues. Methods: The analytic samples were precipitated by methanol in one step and separated using a reverse-phase Poroshell 120 EC-C18 column (4.6 mm×50 mm; 2.7 μm). And the mobile gradient phase at a flow rate of 0.6 mL/min was composed of acetonitrile and 0.1% formic acid in water. The quantitative detection was achieved by multiple-reaction monitoring mode with a positive electrospray ionization source, transitional ion pairs of m/z 265.9>184.8 for trans-loxoprofenalcohol, and 268.8>187.9 for rac-trans-loxoprofen-D3 alcohol (Internal standard). Results: A good linearity of calibration curves for plasma and tissues was observed in the concentration range from 5.0 to 5000 ng/mL, and the lower limit of quantification was detected at 5.0 ng/mL. The intra-day and inter-day precision in plasma and tissues were within 8.94% and 7.26%, respectively. The mean extraction recovery and matrix effects in plasma and tissues were in the range of 89.08~109.27% and 89.00~106.80%, respectively. Precision of stability in plasma and tissues was within 8.91% and 7.08%, respectively. Conclusion: Complying with the requirements of bioanalytical guidelines by validation, this method was successfully adopted to the toxicokinetics and tissue distribution study after intravenously administrated trans-loxoprofen-alcohol into pregnant SD rats.
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- 2022
3. Targeted 19F-tags to detect amino acids in complex mixtures using NMR spectroscopy
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Keeton Montgomery, Aya Elhabashy, Guanglin Chen, Qiao-Hong Chen, and V.V. Krishnan
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Inorganic Chemistry ,Organic Chemistry ,Environmental Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2023
4. Pharmacokinetics of Recombinant Human Growth Hormone (rhGH) in Beagles by ELISA
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Qian Yueyue, Xu Quanyu, Shao Qing, and Qiao Hong-qun
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Chemistry ,Human growth hormone ,030232 urology & nephrology ,Biophysics ,Pharmaceutical Science ,030209 endocrinology & metabolism ,Pharmacology ,Biochemistry ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,law ,Recombinant DNA ,Molecular Medicine - Abstract
Background:: Somatropin is recombinant human growth (GH) used for the treatment of growth failure in children and GH deficiency in adults. At present, rhGH marketed in China is mostly freeze-dried powder injection. As the lyophilization process is unstable, time-consuming and costly, rhGH has been prepared into an aqueous solution for administering directly. Introduction:: In this study, the pharmacokinetics of two dosage forms of rhGH in beagle dogs after single subcutaneous administration was determined by enzyme-linked immunosorbent assay (ELISA). Methods: Twelve healthy beagles (male, 6:female, 6) were used for the pharmacokinetic study and were equally divided into two groups. Subcutaneous injection of 0.2 IU/kg with rhGH in the two formulations. The blood samples were taken from forearms, 0, 0.033, 0.083, 0.25, 0.5, 1, 2, 3, 4, 7, 10, 24 h and collected the beagle plasma on time. The pharmacokinetic parameters of rhGH after subcutaneous (s.c.) injection were determined experimentally on beagles. Primary PK endpoints were area under the serum concentration-time curve (AUC0-t) and maximum serum concentration (Cmax). Serum rhGH level was determined by enzyme-linked immunosorbent assay. Results:: The calibration curves obtained were linear over the concentration range of 25 to 1600 ng/ml for recombinant human growth. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. The analysis samples were stable under different storage conditions and temperature. Conclusions:: The developed ELISA method has been successfully applied to the studies of pharmacokinetic of recombinant human growth hormone in beagles.
- Published
- 2020
5. A Quantitative LC-MS/MS Method for Determination of Liposomal Amphotericin B in Rat Plasma and Tissues and its Application to a Toxicokinetic and Tissue Distribution Study
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Qian Yueyue, Yuan Yanjuan, He Xuejun, Shao Qing, Qiao Hong-qun, and Xu Quanyu
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0303 health sciences ,Chromatography ,030309 nutrition & dietetics ,Chemistry ,Biophysics ,Pharmaceutical Science ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Biochemistry ,03 medical and health sciences ,Lc ms ms ,Molecular Medicine ,Toxicokinetics ,Liposomal amphotericin ,Tissue distribution ,0210 nano-technology - Abstract
Background:: Among the existing antifungal drugs, Amphotericin B is the first drug in the treatment of systemic fungal infections. However, its large adverse reactions limit the clinical application and Liposome Amphotericin B resolves the problem. Objective:: In the present study, a rapid, simple, sensitive and efficient method based on LCMS/ MS for determination of liposomal Amphotericin B in rat plasma and tissue samples using natamycin as the internal standard has been developed and validated. Methods: The analytical samples contain the plasma and various tissues disposed of by protein precipitation and determination of liposomal Amphotericin B by an LC-MS/MS. Chromatographic separation was achieved on a Poroshell 120 EC-C18 column (4.6 mm × 50 mm, 2.7 μm) with 10 mmol/L ammonium acetate in water-acetonitrile by gradient elution at a flow rate of 0.7 mL/min. The MS analysis was conducted in positive electrospray ionization with Multiple Reaction Monitoring (MRM). Results:: The calibration curves of plasma and tissues showed good linear range from 50 to 10000 ng/mL. The analytical samples containing plasma and tissues were stable under different storage conditions and temperature. Conclusions: : The developed LC-MS/MS method has been successfully applied to the studies of toxicokinetics and tissue distribution after intravenous injection of liposomal Amphotericin B to rats.
- Published
- 2020
6. 5-Substituted 3, 3', 4', 7-tetramethoxyflavonoids - A novel class of potent DNA triplex specific binding ligands
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Vanessa M. Rangel, Landy Gu, Guanglin Chen, Qiao-Hong Chen, and Liang Xue
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Biological Products ,Binding Sites ,Molecular Structure ,Organic Chemistry ,Clinical Biochemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,DNA ,Ligands ,Molecular Biology ,Biochemistry - Abstract
Herein, we present a class of potent triplex DNA binding ligands derived from the natural product quercetin, which is the first of its kind that has ever been reported in the literature. The binding of 5-substituted quercetin derivatives (3, 3', 4', 7-tetramethoxyflavonoids) to triplex and duplex DNA was investigated using several biophysical tools, including thermal denaturation monitored by UV, circular dichroism, differential scanning calorimetry, and isothermal titration calorimetry. Experimental data reveal that several 5-substituted 3, 3', 4', 7-tetramethoxyflavonoids have remarkable effects on binding to DNA triple helices, and they do not influence the double-helical DNA structures. A few derivatives such as compounds 5 and 7 have comparable (if not better) binding affinities to neomycin, a well-known DNA triplex binding ligand, under the same conditions. The amino-containing side chains at the 5-position of 3, 3', 4', 7-tetramethoxyflavonoids are crucial for the observed binding affinity and specificity.
- Published
- 2021
7. Synthesis and biological evaluation of niclosamide PROTACs
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Erick, Munoz, Guanglin, Chen, Ahamed, Hossain, Sitong, Wu, Esveidy, Oceguera Nava, Jasmine, Hang, Tong, Lee, Qiang, Zhang, Guangdi, Wang, and Qiao-Hong, Chen
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Male ,Ubiquitin-Protein Ligases ,Organic Chemistry ,Clinical Biochemistry ,Prostatic Neoplasms ,Pharmaceutical Science ,Ligands ,Biochemistry ,Receptors, Androgen ,Proteolysis ,Drug Discovery ,Humans ,Niclosamide ,Molecular Medicine ,Molecular Biology - Abstract
Roughly 268,000 new cases of prostate cancer and 34,000 deaths from prostate cancer are projected by the American Cancer Society to occur in the United States in 2022. Androgen receptor is a key protein in the proliferation and survival of prostate cancer cells and has been revealed to be overexpressed in 30% to 50% of castration-resistant prostate cancer patients. One promising approach to reducing the level of this protein is Proteolysis Targeting Chimeras (PROTACs) that is an emerging drug discovery technology. PROTACs are hetero-bifunctional molecules where one end binds to a protein of interest and the other to an E3 ligase ligand, initiating the Ubiquitin-Proteasome Pathway for protein degradation. Two PROTACs with niclosamide as androgen receptor ligand and VHL-032 as the E3 ligase ligand have been designed and synthesized for suppressing proliferation of androgen receptor-positive prostate cancer cells via degrading androgen receptor. The in vitro antiproliferative assessment suggested that they can selectively suppress PC-3, LNCaP, and 22Rv1 prostate cancer cell proliferation, but cannot inhibit DU145 cell proliferation. However, the mechanism of both compounds in suppressing prostate cancer cell proliferation is not through the AR PROTAC mechanism because they did not degrade AR in our Western Blotting assay up to 1 µM.
- Published
- 2022
8. Physicochemical characteristics and antioxidant activities of non-starch polysaccharides from different kiwifruits
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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.
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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. Effects of extraction methods on the physicochemical characteristics and biological activities of polysaccharides from okra (Abelmoschus esculentus)
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Wen Liu, Qing Zhang, Xi-Rui Nie, Wen Qin, Shang Lin, Su Yan, Qiao-Hong Han, Qin Yuan, Ding-Tao Wu, Li Zhao, Yuan Fu, and Derong Lin
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Antioxidant ,medicine.medical_treatment ,02 engineering and technology ,Polysaccharide ,Biochemistry ,03 medical and health sciences ,Abelmoschus ,Polysaccharides ,Structural Biology ,medicine ,Monosaccharide ,Glycoside Hydrolase Inhibitors ,Food science ,Molecular Biology ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Molecular mass ,biology ,Extraction (chemistry) ,alpha-Glucosidases ,Water extraction ,General Medicine ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Hot water extraction ,chemistry ,alpha-Amylases ,0210 nano-technology - Abstract
The impacts of three extraction techniques, including hot water extraction (HWE), pressurized water extraction (PWE), and microwave assisted extraction (MAE), on the physicochemical characteristics, antioxidant activities, in vitro binding properties, and in vitro inhibitory activities on α-amylase and α-glucosidase of okra polysaccharides (OPPs) were investigated and compared. The extraction yields, constituent monosaccharides, and FT-IR spectra of OPP-W, OPP-P, and OPP-M extracted by HWE, PWE, and MAE, respectively, were similar. However, their molecular weights, intrinsic viscosities, uronic acids, and degree of esterification were different. Furthermore, results showed that OPP-W, OPP-P, and OPP-M exhibited remarkable antioxidant activities, binding capacities, and inhibitory activities on α-amylase and α-glucosidase. Indeed, the antioxidant activities of OPP-W were significantly lower than those of OPP-M and OPP-P, which might be attributed to the low molecular weights and high contents of unmethylated galacturonic acid of OPP-P and OPP-M. However, the binding capacities and inhibitory activities on α-amylase and α-glucosidase of OPP-W and OPP-P were similar, but significantly higher than those of OPP-M, which might be attributed to the low molecular weights of OPP-M. Results suggested that the PWE method could be a good potential technique for the extraction of OPPs with high bioactivities for industrial applications.
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- 2019
11. 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
12. Difference of proteomics vernalization-induced in bolting and flowering transitions of Beta vulgaris
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Qiao-Hong Liu, Dayou Cheng, Chengfei Luo, Liang Naiguo, and Jie Cui
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Proteomics ,0301 basic medicine ,Bolting ,Phenylpropanoid ,biology ,Physiology ,fungi ,Quantitative proteomics ,food and beverages ,Flowers ,Plant Science ,Vernalization ,biology.organism_classification ,03 medical and health sciences ,030104 developmental biology ,Biochemistry ,Germination ,Genetics ,Gibberellin ,Hormone metabolism ,Sugar beet ,Beta vulgaris ,Plant Proteins - Abstract
Sugar beet (Beta vulgaris) is a biennial crop that accounts for 30% sugar production of the world. Vernalization is an essential factor for sugar beet reproductative growth under long days. Although genes association with bolting and flowering were well explored, the difference of proteomics in the two growth stages were still poorly understood. To address the molecular mechanism at the level of proteins, an isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach was employed to the three different growth stages (germination, bolting, flowering) of vernalized samples and the corresponding stage germination (17W weeks), 19W and 20W of nonvernalized samples. A total of 1110 peptides, 842 unique peptides and 570 proteins were identified. Most of them were assigned to phenylpropanoid biosynthesis, hormone metabolism and protein processing pathway. IAA and Gibberellins (GA3) promoted growth and development in a threshold manner at growth stage germination after vernalization. A novel discovery was that IAA biosynthetic pathway of sugar beet was the Trp-dependent. In addition, two predominant pathways of protein processing association with vernalization were also identified in sugar beet at growth stage flowering. This study provided an in-depth understanding of the molecular mechanism of vernalization at the level of proteomics.
- Published
- 2018
13. 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
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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
14. An amide mimic of desTHPdactylolide: Total synthesis and antiproliferative evaluation
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Guanglin Chen, Maricarmen Gonzalez, Guangdi Wang, Qiang Zhang, Ziran Jiang, and Qiao-Hong Chen
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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
15. 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
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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
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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
16. 5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models
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Guangdi Wang, Xiaojie Zhang, Nandini Nair, Bao Vue, Sheng Zhang, Shilong Zheng, Guanglin Chen, Qiang Zhang, Timmy Lee, and Qiao-Hong Chen
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Male ,0301 basic medicine ,medicine.medical_specialty ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Article ,Flow cytometry ,Structure-Activity Relationship ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,DU145 ,Cell Line, Tumor ,Internal medicine ,Drug Discovery ,LNCaP ,medicine ,Humans ,Potency ,Molecular Biology ,Cell Proliferation ,medicine.diagnostic_test ,Cell growth ,Chemistry ,Organic Chemistry ,Prostatic Neoplasms ,Cell cycle ,medicine.disease ,G1 Phase Cell Cycle Checkpoints ,030104 developmental biology ,Endocrinology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Silymarin - Abstract
To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles. Our WST-1 cell proliferation assay data indicate that nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved antiproliferative potency as compared with silybin toward both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O-Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can consistently inhibit cell proliferation in three prostate cancer cell models with all IC50 values lower than 8 μM. Our flow cytometry-based assays also demonstrate that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the G0/G1 phase and activates PC-3 cell apoptosis.
- Published
- 2017
17. Extraction, antioxidant and antibacterial activities of Broussonetia papyrifera fruits polysaccharides
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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
18. Fluorinated bisbenzimidazoles: a new class of drug-like anion transporters with chloride-mediated, cell apoptosis-inducing activity
- Author
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Wen-Hua Chen, Xiao-Qiao Hong, and Xi-Hui Yu
- Subjects
Halogenation ,Apoptosis ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Chloride ,Structure-Activity Relationship ,Chlorides ,Cell Line, Tumor ,medicine ,Structure–activity relationship ,Humans ,Cellular anion homeostasis ,Physical and Theoretical Chemistry ,Cytotoxicity ,Liposome ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Hydrogen Bonding ,0104 chemical sciences ,Drug Design ,Cancer cell ,Lipophilicity ,Biophysics ,Bisbenzimidazole ,Hydrophobic and Hydrophilic Interactions ,medicine.drug - Abstract
Anion transporters have attracted substantial interest due to their ability to induce cell apoptosis by disrupting cellular anion homeostasis. In this paper we describe the synthesis, anion recognition, transmembrane anion transport and cell apoptosis-inducing activity of a series of fluorinated 1,3-bis(benzimidazol-2-yl)benzene derivatives. These compounds were synthesized from the condensation of 1,3-benzenedialdehyde or 5-fluoro-1,3-benzenedialdehyde with the corresponding 1,2-benzenediamines and fully characterized. They are able to form stable complexes with chloride anions, and exhibit potent liposomal and in vitro anionophoric activity. Their anion transport efficiency may be ameliorated by the total number of fluorine atoms, and the enhanced anionophoric activity was a likely consequence of the increased lipophilicity induced by fluorination. Most of these fluorinated bisbenzimidazoles exhibit potent cytotoxicity toward the selected cancer cells. Mechanistic investigations suggest that these compounds are able to trigger cell apoptosis probably by disrupting the homeostasis of chloride anions.
- Published
- 2019
19. 3- O -Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells
- Author
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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
20. Synthesis and biological effect of lysosome-targeting fluorescent anion transporters with enhanced anionophoric activity
- Author
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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
21. Synthesis and evaluation of isoprenylation-resveratrol dimer derivatives against Alzheimer's disease
- Author
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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
22. Optimization of diarylpentadienones as chemotherapeutics for prostate cancer
- Author
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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
23. Optimized synthesis and antiproliferative activity of desTHPdactylolides
- Author
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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
24. Novel 8-hydroxyquinoline derivatives targeting β-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease
- Author
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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
25. A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation
- Author
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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
26. Genome-wide Screening of Human Papillomavirus-Specific CTL Epitopes Presented by HLA-A Alleles in Cervical Cancer
- Author
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Zhang Lili, Li Yao, Yu-Hong Xia, Xi-Hong Zhang, Bei-Bei Liu, Xue-Ling Lou, Zhan-Xin Zhang, Xiang-Yang Gao, and Qiao-Hong Wang
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Virtual screening ,Bioengineering ,Peptide binding ,Peptide ,Computational biology ,Human leukocyte antigen ,Biology ,Biochemistry ,Genome ,Virology ,Epitope ,Analytical Chemistry ,HLA-A ,03 medical and health sciences ,030104 developmental biology ,chemistry ,Drug Discovery ,Molecular Medicine ,Cytotoxic T cell - Abstract
Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, which can increase the risk of cervical cancer. Development of HPV-specific vaccines that can be recognized and presented by human leukocyte antigen (HLA) system is considered as an important approach to prevention and treatment of cervical cancer. In this study, a combination of bioinformatics analysis and peptide binding assay was described to identify potential cytotoxic T lymphocyte epitopes from the HPV genome. In the procedure, a structure-based quantitative structure–activity relationship (SB-QSAR) was used to analyze the intermolecular interactions between HLA proteins and peptide epitopes, and the obtained nonbonded descriptors were then correlated linearly and nonlinearly with HLA–peptide affinities by using partial least squares regression and support vector machine, respectively. Several SB-QSAR models were established and evaluated rigorously, from which the best predictor was applied to virtual screening against thousands of nonapeptide segments generated from the HPV-16 genome. With this protocol a number of peptide ligands were inferred to have high affinity for a variety of frequently observed HLA-A alleles, including 0101, 0201, 0202, 0203, 0206 and 0301, from which several promising candidates were selected and tested in vitro to determine their binding strength toward HLA proteins. Consequently, several peptides were identified as potent HLA binders with half-maximal binding BL50 at micromolar level. The molecular mechanism underlying the high-affinity binding of identified peptide ligands to HLA proteins was also investigated in detail.
- Published
- 2015
27. Targeting miR-21 sensitizes Ph+ ALL Sup-b15 cells to imatinib-induced apoptosis through upregulation of PTEN
- Author
-
Man-Yu Liu, Weizhang Wang, Jianwen Mao, Qing-Qing Wu, Li Li, Xiaobao Jin, Qiao-Hong Pu, Xiang-Hua Lin, Li-Rong Wu, and Jiayong Zhu
- Subjects
medicine.drug_class ,Oligonucleotides ,Biophysics ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Tyrosine-kinase inhibitor ,Downregulation and upregulation ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,medicine ,Humans ,PTEN ,RNA, Small Interfering ,Protein Kinase Inhibitors ,neoplasms ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,biology ,Chemistry ,PTEN Phosphohydrolase ,Antagomirs ,Imatinib ,Cell Biology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Molecular biology ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Drug Resistance, Neoplasm ,Cell culture ,Imatinib Mesylate ,Cancer research ,biology.protein ,RNA Interference ,medicine.drug - Abstract
Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) cells are insensitive to BCR-ABL tyrosine kinase inhibitor imatinib, the underlying mechanisms remain largely unknown. Here, we showed that imatinib treatment induced significant upregulation of miR-21 and downregulation of PTEN in Ph+ ALL cell line Sup-b15. Transient inhibition of miR-21 resulted in increased apoptosis, PTEN upregulation and AKT dephosphorylation, whereas ectopic overexpression of miR-21 further conferred imatinib resistance. Furthermore, knockdown of PTEN protected the cells from imatinib-induced apoptosis achieved by inhibition of miR-21. Additionally, PI3K inhibitors also notably enhanced the effects of imatinib on Sup-b15 cells and primary Ph+ ALL cells similar to miR-21 inhibitor. Therefore, miR-21 contributes to imatinib resistance in Ph+ ALL cells and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to imatinib therapy.
- Published
- 2014
28. Rational Design and Multibiological Profiling of Novel Donepezil-Trolox Hybrids against Alzheimer's Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties
- Author
-
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
29. Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease
- Author
-
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
30. 3-O-Substituted-3',4',5'-trimethoxyflavonols: Synthesis and cell-based evaluation as anti-prostate cancer agents
- Author
-
Xiang Li, Guangdi Wang, Maizie Lee, Qiao-Hong Chen, Shilong Zheng, Guanglin Chen, and Qiang Zhang
- Subjects
0301 basic medicine ,Male ,Flavonols ,Clinical Biochemistry ,Cell ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Article ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,DU145 ,Cell Line, Tumor ,Drug Discovery ,LNCaP ,medicine ,Potency ,Humans ,Molecular Biology ,Cell Proliferation ,Cell growth ,Chemistry ,Organic Chemistry ,Prostatic Neoplasms ,Cell Cycle Checkpoints ,Cell cycle ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
Twenty-two 3- O -substituted-3′,4′,5′-trimethoxyflavonols have been designed and synthesized for their anti-proliferative activity towards three human prostate cancer cell lines. Our results indicate that most of them are significantly more potent than the parent 3′,4′,5′-trimethoxyflavonol in inhibiting the cell proliferation in PC-3 and LNCaP prostate cancer cell models. 3- O -Substituted-3′,4′,5′-trimethoxyflavonols have generally higher potency towards PC-3 and LNCaP cell lines than the DU145 cell line. Incorporation of an ethyl group to 3-OH of 3′,4′,5′-trimethoxyflavonol leads to 3- O -ethyl-3′,4′,5′-trimethoxyflavonol as the optimal derivative with up to 36-fold enhanced potency as compared with the corresponding lead compound 3′,4′,5′-trimethoxyflavonol, but with reversed PC-3 cell apoptotic response. Introduction of a dipentylaminopropyl group to 3-OH increases not only the antiproliferative potency but also the ability in activating PC-3 cell apoptosis. Our findings imply that modification on 3-OH of trimethoxyflavonol can further enhance its in vitro anti-proliferative potency and PC-3 cell apoptosis induction.
- Published
- 2017
31. Synthesis and pharmacological evaluation of multi-functional homoisoflavonoid derivatives as potent inhibitors of monoamine oxidase B and cholinesterase for the treatment of Alzheimer's disease† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available. See DOI: 10.1039/c7md00199a
- Author
-
Xue-Lian Yang, Pei Cai, Qiao-Hong Liu, Xiao-Bing Wang, Ling-Yi Kong, Jia-Jia Wu, and Fan Li
- Subjects
0301 basic medicine ,Monoamine oxidase ,Aché ,Pharmaceutical Science ,Pharmacology ,Inhibitory postsynaptic potential ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Non-competitive inhibition ,Drug Discovery ,IC50 ,Cholinesterase ,biology ,Organic Chemistry ,Acetylcholinesterase ,language.human_language ,Chemistry ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,language ,Molecular Medicine ,Monoamine oxidase B - Abstract
A series of homoisoflavonoid derivatives was designed, synthesized and evaluated as potential multi-functional anti-Alzheimer's agents for their inhibitory activity on cholinesterase and monoamine oxidase. Among them, compound 16 showed moderate acetylcholinesterase (AChE) inhibitory activity (eeAChE IC50 = 0.89 ± 0.02 μM; hAChE IC50 = 0.657 ± 0.002 μM) and significant monoamine oxidase B (MAO-B) inhibitory activity (hMAO-B IC50 = 0.0372 ± 0.0002 μM). Kinetic analysis of AChE, MAO-B inhibition and molecular modeling studies revealed that compound 16 is a dual binding site inhibitor of AChE and noncompetitive inhibitor of MAO-B. Furthermore, 16 could penetrate through the blood–brain barrier (BBB) in vitro. Most importantly, oral administration of 16 demonstrated no marked signs of acute toxicity and it could significantly reverse scopolamine-induced memory impairment in mice. These results suggested that compound 16 is a promising multifunctional drug candidate with potential effect for the treatment of Alzheimer's disease.
- Published
- 2017
32. Effects of Melatonin on Anti-oxidative Systems and Photosystem II in Cold-Stressed Rice Seedlings
- Author
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Lijun Zhou, Jinqiu Liao, Ming Yuan, Zhong-Wei Zhang, Shu Yuan, Bo Huang, Chunbang Ding, Qiao-Hong Han, Yang-Er Chen, Chao Hu, and Yan Huang
- Subjects
0106 biological sciences ,0301 basic medicine ,Antioxidant ,Photosystem II ,medicine.medical_treatment ,melatonin ,Plant Science ,Biology ,lcsh:Plant culture ,Photosynthesis ,01 natural sciences ,Melatonin ,03 medical and health sciences ,chemistry.chemical_compound ,medicine ,lcsh:SB1-1110 ,Food science ,Chlorophyll fluorescence ,Photosystem ,Original Research ,chemistry.chemical_classification ,reactive oxygen species ,Reactive oxygen species ,chlorophyll fluorescence ,food and beverages ,photosynthetic parameters ,Malondialdehyde ,030104 developmental biology ,chemistry ,Biochemistry ,cold stress ,hormones, hormone substitutes, and hormone antagonists ,010606 plant biology & botany ,medicine.drug - Abstract
Melatonin (N-acetyl-5-methoxytryptamine) plays important role in multiple plant developmental processes and stress responses. We investigated the possible mediatory role of melatonin in growth, photosynthesis, and the response to cold stress in rice by using three different experiments: soaking seed; immersing roots, and spraying to leaves with 0, 20 or 100 μM melatonin. After 6 days of cold stress, the growth of rice seedlings was significantly inhibited, but this inhibition was alleviated by exogenous melatonin. Furthermore, exogenous melatonin pretreatment alleviated the accumulation of reactive oxygen species (ROS), malondialdehyde and cell death induced by cold stress. Melatonin pretreatment also relieved the stress-induced inhibitions to photosynthesis and photosystem (PS) II activities. Further investigations showed that, antioxidant enzyme activities and non-enzymatic antioxidant levels were increased by melatonin pretreatments. The treatment methods of seed soaking and root immersion were more effective in improving cold stress resistance than the spraying method. The results also indicated the dose-dependent response of melatonin on rice physiological, biochemical and photosynthetic parameters.
- Published
- 2017
33. Synthesis and pharmacological evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease
- Author
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Qiao-Hong Liu, Xue-Lian Yang, Pei Cai, Ling-Yi Kong, Jin Wang, Jia-Jia Wu, Xiao-Bing Wang, and Fan Li
- Subjects
Antioxidant ,Monoamine Oxidase Inhibitors ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Apoptosis ,Pharmacology ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,PC12 Cells ,Antioxidants ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,Alzheimer Disease ,Drug Discovery ,medicine ,Animals ,Humans ,Chelation ,Molecular Biology ,IC50 ,Monoamine Oxidase ,Amyloid beta-Peptides ,Binding Sites ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Hydrogen Peroxide ,In vitro ,0104 chemical sciences ,Protein Structure, Tertiary ,Rats ,Metal chelation ,Molecular Docking Simulation ,Inhibitory potency ,Oxidative Stress ,Neuroprotective Agents ,Blood-Brain Barrier ,Chromones ,Chromone ,Molecular Medicine ,Reactive Oxygen Species ,Oxidative stress ,Copper - Abstract
In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC50 value of 5.12μM for hMAO-A and 0.816μM for hMAO-B), moderate inhibition of Aβ aggregation (75.1% at 20μM), metal chelation, control of ROS generation and antioxidant activity (ORAC=3.62). In addition, s19 could reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results suggested that s19 might be a promising multitargeted compound for AD treatment.
- Published
- 2017
34. Total synthesis of fuzinoside
- Author
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Feng-Peng Wang, Jing-Song Yang, Qiao-Hong Chen, Ping He, and Xiao-Huan Li
- Subjects
Chromatography ,biology ,Organic Chemistry ,Total synthesis ,Cardiac activity ,biology.organism_classification ,Biochemistry ,Nmr data ,chemistry.chemical_compound ,chemistry ,Bullfrog ,Galactose ,Yield (chemistry) ,Drug Discovery ,Aconitum - Abstract
The first total syntheses of fuzinoside (1b) were achieved from d -galactose through two strategies (BCA and ABC) in 11 (total yield: 5.0%) and 15 (total yield: 3.7%) steps, respectively. Comparison of NMR data of synthetic compound 1b and those of the fuzinoside isolated from the lateral roots of Aconitum carmicaelii suggests that the structure reported in the literature 1 , 2 might not be accurate. The synthetic fuzinoside (1b) exhibited moderate cardiac activity in the isolated bullfrog heart assay.
- Published
- 2014
35. Further revisions on the diterpenoid alkaloids reported in a JNP paper (2012, 75, 1145–1159)
- Author
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Hong-Ying Deng, Feng-Peng Wang, Dong-Lin Chen, Xi-Xian Jian, Xiao-Yu Liu, and Qiao-Hong Chen
- Subjects
biology ,Chemistry ,Stereochemistry ,Chemical shift ,Alkaloid ,Organic Chemistry ,biology.organism_classification ,Biochemistry ,Nmr data ,Terpenoid ,Aconitum carmichaelii ,chemistry.chemical_compound ,Drug Discovery ,Acetone - Abstract
We have corrected (Tetrahedron 2013, 69, 5859–5866) the structures of diterpenoid alkaloids reported in the Journal of Natural Products 2012, 75, 1145–1159. Our follow-up experiments compel us to present further revisions and clarifications on the diterpenoid alkaloids: (1) The naturally occurring forms of carmichaelines B, C, and D in Shi's paper (Journal of Natural Products 2012, 75, 1145–1159) are neither quaternary ammonium hydroxides 2–4 nor the initially revised trifluoroacetates. They are indeed the vakognavine-type C20-diterpenoid alkaloids 11–13. (2) The samples' concentration is the critical factor to the signals' intensity for F3CCOO− in the alkaloid trifluoroacetates. Incorporation of TFA into the corresponding salts resulted in signals' enhancement due to the closeness of δ values (∼116 ppm, ∼159 ppm) of free TFA and those of F3CCOO−. After removal of free TFA, the carbon signals of CF3COO− could become weaker, but their chemical shifts remained almost unchanged. The possible reason might be the ionization of TFA in acetone. (3) The NMR data cannot distinguish TFA from trifluoroacetates (e.g., F3CCOONa and C19-diterpenoid alkaloid trifluoroacetates), indicating that the signal at around δ −76 cannot be used to exclude the existence of trifluoroacetates. In addition to the NMR and CSI-MS data, 1H–15N HMBC technique was also used to distinguish the free alkaloids from their trifluoroacetates. (4) The X-ray crystallographic analysis of compound 20 confirmed that the ‘new alkaloid’ (-b) in the Shi's paper is indeed the known compound aconifine trifluoroacetate. (5) Collectively, Shi's paper mixed-up the free alkaloids with their salts and the concepts of structure and conformation. Naming different structures with A-b and A-c is also confusing.
- Published
- 2014
36. Natural Product Reports
- Author
-
David G. I. Kingston, Qiao-Hong Chen, Chemistry, Virginia Tech. Department of Chemistry, Center for Drug Discovery, and California State University, Fresno. Department of Chemistry
- Subjects
Bridged-Ring Compounds ,Zampanolide ,Paclitaxel ,Stereochemistry ,Antineoplastic Agents ,Marine Biology ,Anti-cancer drugs ,010402 general chemistry ,Microtubules ,01 natural sciences ,Biochemistry ,Lactones ,chemistry.chemical_compound ,Tubulin ,Microtubule ,Drug Discovery ,medicine ,Cytotoxic T cell ,Cytotoxic agents ,Cytotoxicity ,Molecular Structure ,biology ,010405 organic chemistry ,Organic Chemistry ,Dactylolide ,Bridged Bicyclo Compounds, Heterocyclic ,3. Good health ,0104 chemical sciences ,Multi-drug resistance ,Chemistry ,Microtubule stabilizing agents ,Mechanism of action ,chemistry ,biology.protein ,Taxoids ,Macrolides ,medicine.symptom - Abstract
Zampanolide and its structural relative dactylolide are promising new tubulin-assembly agents with the potential to become new anticancer drugs. This review covers their sources and isolation, structures, anticancer potential, mechanism of action, and syntheses., Covering: through January 2014 Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability. This review provides an overview of current developments of zampanolide and its related but less potent analogue dactylolide, covering their natural sources and isolation, structure and conformation, cytotoxic potential, structure–activity studies, mechanism of action, and syntheses.
- Published
- 2014
37. Revisions of the diterpenoid alkaloids reported in a JNP paper (2012, 75, 1145–1159)
- Author
-
Qi-Feng Chen, Zhong-Tang Zhang, Xiao-Yu Liu, Qiao-Hong Chen, Feng-Peng Wang, Dong-Lin Chen, and Ling Wang
- Subjects
Stereochemistry ,Chemistry ,Organic Chemistry ,Drug Discovery ,Cyclohexane conformation ,Free base ,Protonation ,DEPT ,Carbon-13 NMR ,Ring (chemistry) ,Biochemistry ,Conformational isomerism ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Eleven C19-diterpenoid alkaloids reported in Shi's paper were isolated or synthesized. Their 13C NMR and DEPT spectra were recorded using (CD3)2CO+TFA as solvents. Comparison of the acquired NMR data with those reported in Shi's paper, in combination with the fact that all alkaloids, expect for 8, 27, and 28, reported in Shi's paper were isolated using TFA as part of solvent system, led to the following revisions of Shi's paper: (1) compounds 1–4, 6, 7a, 9–26 should be their respective trifluoroacetates. Their structures were revised as 1a–4a, 6a, 7a′, 9a–26a; (2) compounds 7, 27a, and 28a are trifluoroacetates of free bases 8, 27, and 28, respectively; compound 7 should be corrected as 7b; (3) ring A of free bases (such as 8, 27, and 28) exists as chair conformation; while ring A of the protonated versions (such as 7, 27a, 28a, 6a, 9a–26a) exists as boat conformation. Consequently, compounds 7 and 8 are apparently not a pair of conformational isomers, instead, they are indeed a free base and its protonated version existing as a trifluoroacetate, respectively; (4) ‘new’ compounds 6, 13, and 15 are the protonated versions 6a, 13a, and 15a, respectively, of the corresponding known alkaloids, aconifine, deoxyaconitine, 14-benzoylaconine. In addition, all 1H (13C) NMR data for the free bases of new compounds 8, 9, 10, 17, and 24 (Tables 3 and 4) were also assigned based on their 2D NMR spectra.
- Published
- 2013
38. Rice protein exerts a hypocholesterolemic effect through regulating cholesterol metabolism-related gene expression and enzyme activity in adult rats fed a cholesterol-enriched diet
- Author
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Chun-Zhi Cheng, Yu-Jun Duan, Guo Han, Qiong Wu, Hongjuan He, Qiao-Hong Liu, and Lin Yang
- Subjects
Male ,medicine.medical_specialty ,7-Dehydrocholesterol reductase ,Hypercholesterolemia ,Sterol O-acyltransferase ,Gene Expression ,Reductase ,Cholesterol, Dietary ,chemistry.chemical_compound ,Internal medicine ,Casein ,Gene expression ,medicine ,Animals ,PPAR alpha ,RNA, Messenger ,Rats, Wistar ,Cholesterol 7-alpha-Hydroxylase ,Liver X Receptors ,Plant Proteins ,Sterol Regulatory Element Binding Proteins ,biology ,Cholesterol ,Anticholesteremic Agents ,Caseins ,Oryza ,Lipid Metabolism ,Orphan Nuclear Receptors ,Enzyme assay ,Sterol ,Diet ,Rats ,Endocrinology ,Liver ,chemistry ,Biochemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Acyl Coenzyme A ,Dietary Proteins ,Sterol O-Acyltransferase ,Food Science - Abstract
The major aim of this study is to elucidate the hypocholesterolemic mechanism exerted by rice protein (RP) in adult rats under cholesterol-enriched dietary condition. Compared with casein, the cholesterol levels in plasma and the liver were significantly reduced by RP, accompanying significant inhibition of cholesterol absorption. RP increased the activity and mRNA level of cholesterol 7α-hydroxylase, whereas acyl-CoA:cholesterol acyltransferase activity and gene expression were significantly depressed with consumption of RP. Neither the activity nor gene expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase of RP differed from that of casein. The gene expression of the peroxisome proliferator-activated receptor α and liver X receptor α were significantly activated by consumption of RP. RP did not modify the mRNA level of sterol regulatory element-binding protein-2 with respect to casein. These results suggest RP can induce a cholesterol-lowering effect through modifying cholesterol metabolism-related gene expression and enzyme activity in adult rats.
- Published
- 2013
39. Bis-Diterpenoid Alkaloids fromAconitum tanguticumvar.trichocarpum
- Author
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Qiao-Hong Chen, Zhong-Tang Zhang, Feng-Peng Wang, and Dong-Lin Chen
- Subjects
Inorganic Chemistry ,Aconitum tanguticum ,Phytochemical ,Traditional medicine ,Chemistry ,Alkaloid ,Organic Chemistry ,Drug Discovery ,Physical and Theoretical Chemistry ,Biochemistry ,Catalysis ,Terpenoid - Abstract
Phytochemical investigation of the whole herbs of Aconitum tanguticum (Maxim.) Stapf var. trichocarpum Hand.-Mazz. led to the isolation of one heteratisine-hetidine-type bis-diterpenoid alkaloid, trichocarpidine (1), three hetidine-hetisine type bis-diterpenoid alkaloids, trichocarpinine A–C (2–4, resp.), together with nine known compounds. Their structures were elucidated by spectroscopic analyses.
- Published
- 2013
40. Effect of oxygen free radicals and nitric oxide on apoptosis of immune organ induced by selenium deficiency in chickens
- Author
-
Zi-wei, Zhang, Jiu-li, Zhang, Yu-hong, Gao, Yu-hong, Zhang, Qiao-hong, Wang, Shu, Li, Xiao-long, Wang, and Shi-wen, Xu
- Subjects
Nitric Oxide Synthase Type II ,Apoptosis ,Spleen ,Biology ,Nitric Oxide ,medicine.disease_cause ,Antioxidants ,General Biochemistry, Genetics and Molecular Biology ,Nitric oxide ,Biomaterials ,Selenium ,chemistry.chemical_compound ,Immune system ,Selenium deficiency ,Malondialdehyde ,medicine ,Animals ,Bursa of Fabricius ,TUNEL assay ,Caspase 3 ,Metals and Alloys ,medicine.disease ,Molecular biology ,Oxidative Stress ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Immune System ,Reactive Oxygen Species ,General Agricultural and Biological Sciences ,Chickens ,Oxidative stress - Abstract
Selenium is an essential element with antioxidant roles in immune regulation, but there is little understanding of how Se acts in apoptosis in the immune organs of birds. The aim of study was to evaluate the influence of Se deficiency on oxygen free radicals, NO and apoptosis in immune organ of chickens. 160 1-day-old chickens were randomly assigned to two groups of 80 each and were fed on a low-Se diet (0.032 mg/kg Se) or a control diet (0.282 mg/kg Se), respectively. OFR production in blood was determined on days 30, 45, 60 and 75, respectively. The iNOS-NO system activity in immune organ (thymus, spleen, bursa of fabricius) was identified by NO content and NOS activity assay on days 30, 45, 60 and 75, respectively. Apoptosis was measured by DNA ladder analysis, ultrastructural observations, TdT-mediated dUTP nick end labeling TUNEL assay and flow cytometric analysis of apoptotic DNA. The transcription of factor-associated suicide, caspase-3 mRNA was tested by fluorescence quantitative PCR. The results showed that OFR production, NO and inducible NO synthases (iNOS) activity in the low-Se group were significantly increased (p < 0.05) than in the control group. In addition, apoptosis was observed in chicken immune organ in the low-Se group. The degree and the number of apoptotic cells rose in a time-dependent manner. The expression of Fas and caspase-3 mRNA increased (p < 0.05) than in the control group. It indicated that the oxidative stress and NO played a causative role in the apoptosis of immune tissues induced by selenium deficiency.
- Published
- 2013
41. Bivalent Carbamates as Novel Control Agents of the Malaria Mosquito, Anopheles gambiae
- Author
-
Maxim Totrov, Dawn M. Wong, Qiao-Hong Chen, Jianyong Li, Polo C-H. Lam, Paul R. Carlier, James M. Mutunga, Jeffrey R. Bloomquist, and Aaron D. Gross
- Subjects
0106 biological sciences ,Peripheral site ,Carbamate ,Insecticides ,Mosquito Control ,medicine.medical_treatment ,Anopheles gambiae ,Catalytic site ,010402 general chemistry ,01 natural sciences ,Bivalent (genetics) ,Anticholinesterase ,Insecticide Resistance ,chemistry.chemical_compound ,Anopheles ,parasitic diseases ,medicine ,Potency ,Animals ,QD1-999 ,Cross-resistance ,biology ,General Medicine ,General Chemistry ,medicine.disease ,biology.organism_classification ,Acetylcholinesterase ,0104 chemical sciences ,Malaria ,010602 entomology ,Chemistry ,Biochemistry ,chemistry ,Active compound ,Drug Design ,Molecular docking ,Carbamates ,Cholinesterase Inhibitors - Abstract
Widespread pyrethroid resistance has caused an urgent need to develop new insecticides for control of the malaria mosquito, Anopheles gambiae. Insecticide discovery efforts were directed towards the construction of bivalent inhibitors that occupy both the peripheral and catalytic sites of the mosquito acetylcholinesterase (AChE). It was hypothesized that this approach would yield a selective, high potency inhibitor that would also circumvent known catalytic site mutations (e.g. G119S) causing target site resistance. Accordingly, a series of bivalent phthalimide-pyrazole carbamates were prepared having an alkyl chain linker of varying length, along with other modifications. The most active compound was (1-(3-(1,3-dioxoisoindolin-2-yl)propyl)-1H-pyrazol-4-yl methylcarbamate, 8a), which has a chain length of three carbons, good mosquito anticholinesterase activity, and ca. 5-fold selectivity compared to human AChE. Moreover, this compound was toxic to mosquitoes by topical application (LD50 = 63 ng/female) with only 6-fold cross resistance in the Akron strain of Anopheles gambiae that showed 50- to 60-fold resistance to conventional carbamate insecticides. However, contact lethality in the WHO paper assay was disappointing. The implications of these results for design of new mosquitocides are discussed.
- Published
- 2016
42. Immune Modulation of Asian Folk Herbal Medicines and Related Chemical Components for Cancer Management
- Author
-
Qiao-Hong Chen and Manee Patanapongpibul
- Subjects
Herbal Medicine ,Biochemistry ,Origin of species ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neoplasms ,Drug Discovery ,Medicine ,Humans ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Cancer prevention ,Traditional medicine ,business.industry ,Plant Extracts ,Organic Chemistry ,Cancer ,Immune modulation ,medicine.disease ,Cancer treatment ,Immune Modulators ,030220 oncology & carcinogenesis ,Immune System ,Cancer management ,Molecular Medicine ,Plants, Edible ,business ,Agaricales - Abstract
Various exciting immunotherapies aiming to address immune deficiency induced by tumor and treatment hold promise in improving the quality of life and survival rate of cancer patients. It is thus becoming an important and rewarding arena to develop some appropriate immune modulators for cancer prevention and/or treatment. Exploitation of natural products-based immune modulators is of particular imperative because the potential of numerous traditional herbal medicines and edible mushrooms in boosting human immune system has long been verified by folklore practices. This review summarizes the immune modulations of various herbal medicines and edible mushrooms, their crude extracts, and/or key chemical components that have been, at least partly, associated with their cancer management. This article also tabulates the origin of species, key chemical components, and clinical studies of these herbal medicines and edible mushrooms.
- Published
- 2016
43. Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease
- Author
-
Pei Cai, Jia-Jia Wu, Zhi-Min Wang, Ling-Yi Kong, Xue-Lian Yang, Qiao-Hong Liu, Kelvin D.G. Wang, and Xiao-Bing Wang
- Subjects
0301 basic medicine ,Parkinson's disease ,Monoamine Oxidase Inhibitors ,Monoamine oxidase ,Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Apoptosis ,Mice, Inbred Strains ,Pharmacology ,Biochemistry ,Neuroprotection ,Cell Line ,Small Molecule Libraries ,03 medical and health sciences ,Mice ,Structure-Activity Relationship ,In vivo ,Drug Discovery ,medicine ,Animals ,Molecular Biology ,Monoamine Oxidase ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Parkinson Disease ,medicine.disease ,Small molecule ,Acute toxicity ,In vitro ,Rats ,030104 developmental biology ,Neuroprotective Agents ,nervous system ,Molecular Medicine - Abstract
The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.
- Published
- 2016
44. Design, Synthesis, and Biological Evaluation of 1,9-Diheteroarylnona-1,3,6,8-tetraen-5-ones as a New Class of Anti-Prostate Cancer Agents
- Author
-
Qiao-Hong Chen, Shilong Zheng, Guanglin Chen, Qiang Zhang, Guangdi Wang, German Ruiz Perez, Xiaojie Zhang, and Rubing Wang
- Subjects
0301 basic medicine ,Male ,Curcumin ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Cell Line, Tumor ,Drug Discovery ,medicine ,Potency ,Humans ,Molecular Biology ,Cell Proliferation ,Cell growth ,Organic Chemistry ,Cell Cycle ,Prostate ,Cancer ,Prostatic Neoplasms ,Cell cycle ,medicine.disease ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Drug Design ,Wittig reaction ,Cancer research ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
In search of more effective chemotherapeutics for the treatment of castration-resistant prostate cancer and inspired by curcumin analogues, twenty five (1E,3E,6E,8E)-1,9-diarylnona-1,3,6,8-tetraen-5-ones bearing two identical terminal heteroaromatic rings have been successfully synthesized through Wittig reaction followed by Horner-Wadsworth-Emmons reaction. Twenty-three of them are new compounds. The WST-1 cell proliferation assay was employed to assess their anti-proliferative effects toward both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Eighteen out of twenty-five synthesized compounds possess significantly improved potency as compared with curcumin. The optimal compound, 78, is 14- to 23-fold more potent than curcumin in inhibiting prostate cancer cell proliferation. It can be concluded from our data that 1,9-diarylnona-1,3,6,8-tetraen-5-one can serve as a new potential scaffold for the development of anti-prostate cancer agents and that pyridine-4-yls and quinolin-4-yl act as optimal heteroaromatic rings for the enhanced potency of this scaffold. Two of the most potent compounds, 68 and 75, effectively suppress PC-3 cell proliferation by activating cell apoptosis and by arresting cell cycle in the G0/G1 phase.
- Published
- 2016
45. A new class of flavonol-based anti-prostate cancer agents: Design, synthesis, and evaluation in cell models
- Author
-
Guangdi Wang, Xiang Li, Xiaojie Zhang, Qiang Zhang, Shilong Zheng, Qiao-Hong Chen, and Guanglin Chen
- Subjects
0301 basic medicine ,Male ,Cell cycle checkpoint ,Flavonols ,Clinical Biochemistry ,Cell ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,Drug Discovery ,medicine ,Structure–activity relationship ,Humans ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Flavonoids ,Cell growth ,Organic Chemistry ,Prostatic Neoplasms ,G2 Phase Cell Cycle Checkpoints ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Drug Design ,Molecular Medicine ,M Phase Cell Cycle Checkpoints ,Quercetin ,Fisetin - Abstract
Flavonoids are a large class of polyphenolic compounds ubiquitously distributed in dietary plants with an array of biological activities. Flavonols are a major sub-class of flavonoids featuring a hydroxyl group at C-3. Certain natural flavonols, such as quercetin and fisetin, have been shown by in vitro cell-based and in vivo animal experiments to be potential anti-prostate cancer agents. However, the Achilles' heel of flavonols as drug candidates is their moderate potency and poor pharmacokinetic profiles. This study aims to explore the substitution effect of 3-OH in flavonols on the in vitro anti-proliferative potency against both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Our first lead flavonol (3',4'-dimethoxyflavonol), eight 3-O-alkyl-3',4'-dimethoxyflavonols, and six 3-O-aminoalkyl-3',4'-dimethoxyflavonols have been synthesized through aldol condensation and the Algar-Flynn-Oyamada (AFO) reaction. The WST-1 cell proliferation assay indicates (i) that all synthesized 3-O-alkyl-3',4'-dimethoxyflavonols and 3-O-aminoalkyl-3',4'-dimethoxyflavonols are more potent than the parent 3',4'-dimethoxyflavonol and the natural flavonol quercetin in suppressing prostate cancer cell proliferation; and (ii) that incorporation of a dibutylamino group to the 3-OH group through a three- to five-carbon linker leads to the optimal derivatives with up to 292-fold enhanced potency as compared with the parent flavonol. Flow cytometry analysis showed that the most potent derivative 22 can activate PC-3 cell cycle arrest at the G2/M phase and induce PC-3 cell apoptosis. No inhibitory ability of 22 up to 50μM concentration was observed against PWR-1E normal human epithelial prostate cells, suggesting its in vitro safety profile. The results indicate that chemical modulation at 3-OH is a vital strategy to optimize flavonols as anti-prostate cancer agents.
- Published
- 2016
46. The Potential of Flavonolignans in Prostate Cancer Management
- Author
-
Bao Vue and Qiao-Hong Chen
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Synthetic derivatives ,Tumor Promoters ,Prostate cancer cell ,Apoptosis ,Biochemistry ,Flavonolignans ,03 medical and health sciences ,Prostate cancer ,Structure-Activity Relationship ,0302 clinical medicine ,Internal medicine ,Small class ,Drug Discovery ,medicine ,Flavonolignan ,Humans ,Prostate tumors ,Pharmacology ,Plants, Medicinal ,business.industry ,Plant Extracts ,Organic Chemistry ,Prostatic Neoplasms ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Silybin ,Cancer research ,Molecular Medicine ,business ,Silymarin - Abstract
Background The generic name "flavonolignan" was created in 1968 for a relatively small class of naturally occurring hybrid molecules biogenetically originated from ubiquitous flavonoids and lignans (phenylpropanoids). The first group of flavonolignans was extracted from Silybum marianum that has long been used for hepatoprotection. Recently, the medicinal merit of flavonolignans has been extended to the prostate cancer management. Methods Systematic interpretation and summarization of the relevant literature. Results Over forty naturally occurring flavonolignans have so far been obtained from various plants. Certain flavonolignans have been demonstrated by in vitro cell-based and in vivo animal-based experiments, and human clinical studies i) to possess effective chemopreventive function against various tumor promoters; ii) to show the anti-angiogenic efficacy; iii) to have potential in treating prostate cancer; iv) to sensitize prostate tumors to chemotherapeutic agents through down-regulation of P-glycoprotein and other mechanisms; and v) to be used by prostate cancer patients to protect or treat the hepatotoxicity caused by several chemotherapies. Certain flavonolignans can synergize with well-established chemotherapeutic agents for prostate cancer. Conclusion This review provides a systematic and in-depth overview of the promise and potential of flavonolignans in prostate cancer management, which covers their chemopreventive effect, chemotherapeutic treatment, mechanisms of actions, synthetic derivatives, structure-activity relationships, and the difference in inhibiting prostate cancer cell proliferation between certain flavonoligans and their respective flavonoid counterpart. This summarization aims to provide valuable insights into further and rational development of flavonolignans for prostate cancer management by interpreting the data reported in the literature.
- Published
- 2016
47. Novel skeletal rearrangements of a diterpene derived from deltaline
- Author
-
Pei Tang, Ling Wang, Xi-Xian Jian, Feng-Peng Wang, Qi-Feng Chen, and Qiao-Hong Chen
- Subjects
chemistry.chemical_compound ,chemistry ,Stereochemistry ,Alkaloid ,Organic Chemistry ,Drug Discovery ,Diterpene ,Ring (chemistry) ,Biochemistry ,Two-dimensional nuclear magnetic resonance spectroscopy ,Terpenoid - Abstract
Treatment of imines 5 and 7 , both prepared from the C 19 -diterpenoid alkaloid deltaline ( 1 ), with NaNO 2 –HCl resulted in the formation of diterpene 6 with an eight-membered ring through a sequence of denitrogenation and enlargement of ring B. In addition, two unusual skeletal rearrangements of diterpene 6 were also observed, leading to two structurally novel products 8 and 10 . The structures of compounds 8 and 10 were confirmed by their X-ray crystallographic analyses and 2D NMR data.
- Published
- 2012
48. New reactivities of deltaline analogs: an efficient O-demethylation at C-1 and an unusual extrusion of the C-14 atom
- Author
-
Feng-Peng Wang, Qiao-Hong Chen, Qi-Feng Chen, Xi-Xian Jian, Pei Tang, and Ling Wang
- Subjects
Grob fragmentation ,Stereochemistry ,Organic Chemistry ,Oxetane ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Atom ,Nucleophilic substitution ,SN2 reaction ,Enone ,Derivative (chemistry) ,Demethylation - Abstract
O-Demethylation at C-1 in the C19-diterpenoid alkaloids is very challenging. In this paper, it was firstly observed that 10-OH group in deltaline (1) is a determining factor for the O-demethylation reaction. After removal of this hydroxyl group, 1-O-methyl group in the corresponding deltaline analogs can be readily removed by treatment with HBr–HOAc. Meanwhile, the C-14 atom in bromides 18 or 20 can be extruded under basic condition probably via a sequence, including Grob fragmentation, aerobic oxidation, deformylation, and SN2 nucleophilic substitution, to give enone 21 (70%) and oxetane 22 (14%). The structure of compound 22 was confirmed by X-ray crystallographic analysis of its derivative 21.
- Published
- 2012
49. Novel reactions of a deltaline analog: an unusual skeletal rearrangement of E/F ring system
- Author
-
Pei Tang, Qi-Feng Chen, Feng-Peng Wang, Ling Wang, Xi-Xian Jian, and Qiao-Hong Chen
- Subjects
chemistry.chemical_classification ,Ketone ,Methanesulfonyl chloride ,Stereochemistry ,Organic Chemistry ,Ring (chemistry) ,Biochemistry ,chemistry.chemical_compound ,Thionyl chloride ,chemistry ,Yield (chemistry) ,Drug Discovery ,Lactam ,Two-dimensional nuclear magnetic resonance spectroscopy ,Lactone - Abstract
Lactam 2, prepared from deltaline (1), is an analog of C19-diterpenoid alkaloid with a hydroxyl group at C-6 and a ketone carbonyl group at C-7. Treatment of this lactam with thionyl chloride or methanesulfonyl chloride, or reaction of this lactam under Chugaev condition led to an unusual rearrangement of its E/F ring system to yield a lactone 10 in a yield range of 43–74%. The structure of 10 was confirmed by its 2D NMR data and X-ray crystallographic analysis.
- Published
- 2012
50. Alkali treatment affects in vitro digestibility and bile acid binding activity of rice protein due to varying its ratio of arginine to lysine
- Author
-
Jia-Hou Chen, Hua Zhang, Lin Yang, Qiao-Hong Liu, Ya-Nan Li, Hong-Kun Yang, Xue Peng, and Wei Qiu
- Subjects
Arginine ,Chemistry ,Lysine ,food and beverages ,Stimulation ,General Medicine ,Bile acid binding ,Alkali metal ,In vitro ,Analytical Chemistry ,Biochemistry ,Rice protein ,Bile-acid Binding Activity ,Food Science - Abstract
To elucidate whether the alkali treatment, which is a common process for rice protein extraction, is responsible for the regulation of digestibility and bile acid binding of rice protein, the effects of different degree of alkali treatment (from 0.1% to 0.3% of NaOH), as well as different ratio of arginine (Arg) to lysine (Lys) by 3.0, 3.5, 4.0, 4.5 and 5.0, which was induced by the addition of Arg to rice protein, on the in vitro digestibility and the bile acid binding activity were investigated. The present study clearly demonstrates the alkali treatment plays a major role in controlling the digestibility and the bile acid binding of rice protein through the modification of amino acid composition. Results indicate that the digestibility and the bile acid binding activity of rice protein are closely varying with the ratio of Arg to Lys. This shows the inhibition of digestibility and stimulation of bile acid binding are enhanced by the increase Arg/Lys ratio through the addition of Arg to rice protein. The present study suggests the Arg/Lys ratio controlled by the concentration of Arg and the alkali treatment may be the main modulator responsible for the physiological function of rice protein involved in cholesterol metabolism.
- Published
- 2012
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