252 results on '"Antitumor Agents"'
Search Results
2. NAD(P)H:Quinone Acceptor Oxidoreductase 1 (NQO1) Activatable Salicylamide H+/Cl− Transporters.
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Roy, Naveen J., Save, Shreyada N., Sharma, Virender Kumar, Abraham, Benchamin, Kuttanamkuzhi, Abhijith, Sharma, Shilpy, Lahiri, Mayurika, and Talukdar, Pinaki
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NAD (Coenzyme) , *MITOCHONDRIAL membranes , *SMALL molecules , *CANCER cells , *OXIDATIVE stress , *CHLORIDE channels - Abstract
NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a detoxifying enzyme overexpressed in tumors, plays a key role in protecting cancer cells against oxidative stress and thus has been considered an attractive candidate for activating prodrug(s). Herein, we report the first use of NQO1 for the selective activation of 'protransporter' systems in cancer cells leading to the induction of apoptosis. Salicylamides, easily synthesizable small molecules, have been effectively used for efficient H+/Cl− symport across lipid membranes. The ion transport activity of salicylamides was efficiently abated by caging the OH group with NQO1 activatable quinones via either ether or ester linkage. The release of active transporters, following the reduction of quinone caged 'protransporters' by NQO1, was verified. Both the transporters and protransporters exhibited significant toxicity towards the MCF‐7 breast cancer line, mediated via the induction of oxidative stress, mitochondrial membrane depolarization, and lysosomal deacidification. Induction of cell death via intrinsic apoptotic pathway was verified by monitoring PARP1 cleavage. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Selective Photodynamic Activity of Tetrakis(4‐aminophenyl)porphyrins with and without Acetyl Protecting Groups on Cancer and Normal Cells.
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Okuno, Masafumi, Yamana, Keita, Kawamura, Shogo, Nishimura, Kotaro, Hino, Shodai, Kawasaki, Riku, and Ikeda, Atsushi
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ACETYL group , *PORPHYRINS , *CANCER cells , *POLYSACCHARIDES , *ZINC porphyrins , *METALLOPORPHYRINS , *SUPRAMOLECULAR chemistry - Abstract
Tetrakis(4‐aminophenyl)porphyrin (1) and tetrakis(4‐acetamidophenyl)porphyrin (2) were dissolved in water with the incorporation of a polysaccharide (λ‐carrageenan (CGN)) as a water‐solubilizing agent. Although the photodynamic activity of the CGN‐2 complex was considerably lower than that of the CGN‐1 complex, the selectivity index (SI; IC50 in a normal cell/IC50 in a cancer cell) of the CGN‐2 complex was considerably higher than that of the CGN‐1 complex. This is because the photodynamic activity of the CGN‐2 complex was significantly affected by the intracellular uptakes by the normal and cancer cells. During in vivo experiments, the CGN‐2 complex inhibited tumor growth under light irradiation with high blood retention compared with the CGN‐1 complex and Photofrin, which exhibited lower blood retention. This study showed that the photodynamic activity and SI are influenced by substituent groups of arene in the meso‐positions of porphyrin analogs. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Synthesis, Theoretical Studies, Cytotoxicity of 2-((4-(Dimethylamino)Benzylidene)Amino)-5-Methylphenol with Potential JNK1 Inhibitory Activity.
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KARAOSMANOĞLU, Oğuzhan, BERBER, Halil, and UYSAL, Ülkü Dilek
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DIMETHYLAMINE , *CISPLATIN , *DRUG resistance in cancer cells , *CANCER cells - Abstract
Cisplatin, doxorubicin, hydroxycamptothecin, leucovorin, vincristine and 5-fluorouracil resistance of cancer cells are associated with the activities of C-Jun N-Terminal Kinase 1 (JNK1). Inhibition of the JNK1 by pharmacological agents could be a beneficial attempt for reversing the chemoresistance of various cancer cells. However, there is no FDA-approved JNK inhibitor for safe use in clinics in today's clinics. In this study, a Schiff base 2-((4-(dimethylamino)benzylidene)amino)-5-methylphenol, (7S4) has been synthesized and characterized by 1H, 13C-NMR, FT-IR and elemental analysis. The stable geometry of 7S4 has been determined by DFT method with Gaussian09 program (B3LYP/6-311g++(d,p))). The Gibbs Free energies, stable tautomer forms, H-bond, Mulliken charges, dipole moment, natural bond orbital (NBO), HOMO, LUMO and band gap energy (EGAP), molecular electrostatic potential (MEP) and solvent accessibility surface areas (SASA) have been calculated. Drug-likeness, anticancer and JNK1 inhibitory activities of 7S4 have been evaluated. Enol tautomer form of trans 7S4 was characterized as the most stable structure. 7S4 was observed to be a reactive compound in chemical reactions with a low EGAP value. In addition, high and low electron density regions of 7S4 are responsible for the establishment of chemical bonds in biological systems. 7S4 exhibited strong druggability with the agreement on Lipinski, Ghose, Veber, Egan, and Muegge rules. Cytotoxicity tests and molecular docking revealed that 7S4 poses a potential JNK1 inhibitor activity. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma.
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Carbone, Daniela, De Franco, Michele, Pecoraro, Camilla, Bassani, Davide, Pavan, Matteo, Cascioferro, Stella, Parrino, Barbara, Cirrincione, Girolamo, Dall'Acqua, Stefano, Moro, Stefano, Gandin, Valentina, and Diana, Patrizia
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PANCREATIC duct , *TRIAZINE derivatives , *TRIAZINES , *MOLECULAR hybridization , *CANCER cells , *ADENOCARCINOMA , *CHEMICAL synthesis - Abstract
Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that all synthesized compounds are potent and subtype-selective inhibitors of PDK. Accordingly, molecular modeling studies revealed that a lot of ligands can be properly placed inside the ATP-binding site of PDK1. Interestingly, 2D and 3D cell studies revealed their ability to induce cancer cell death at low micromolar doses, being extremely effective against human pancreatic KRAS mutated cancer cells. Cellular mechanistic studies confirm their ability to hamper the PDK/PDH axis, thus leading to metabolic/redox cellular impairment, and to ultimately trigger apoptotic cancer cell death. Remarkably, preliminary in vivo studies performed on a highly aggressive and metastatic Kras-mutant solid tumor model confirm the ability of the most representative compound 5i to target the PDH/PDK axis in vivo and highlighted its equal efficacy and better tolerability profile with respect to those elicited by the reference FDA approved drugs, cisplatin and gemcitabine. Collectively, the data highlights the promising anticancer potential of these novel PDK-targeting derivatives toward obtaining clinical candidates for combatting highly aggressive KRAS-mutant pancreatic ductal adenocarcinomas. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Design, Synthesis, and In Vitro Anticancer Activity of Triazolyl Analogs of Abietic Acid.
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Ali, G. and Ara, T.
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ABIETIC acid , *BREAST , *ANTINEOPLASTIC agents , *CANCER cells , *CELL lines , *CHEMICAL synthesis - Abstract
A series of abietic acid analogs modified with a triazole moiety were synthesized using Huisgen 1,3-dipolar cycloaddition in order to obtain potent antitumor agents. The synthesized compounds and starting materials were tested in vitro against four human cancer cell lines, MDA-MB-231 and MCF-7 (human breast cancer cells), A549 (human lung cancer), PC3 (human prostate cancer), and FR2 (non-tumor human breast epithelial cell line) by MTT assay. Some of the synthesized analogs showed better biological profiles than that of the precursors. The most active compound (4-hydroxyphenyl derivative) showed an IC50 value of 35.4 µM against MDA-MB-231 cancer cell line. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Proteolysis Targeting Chimeras (PROTACs) Based on Promiscuous Kinase Inhibitor Synergistically Induce Cancer Cell Apoptosis Through Multiple Mechanisms.
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Zhai, Jiadai, Li, Chuang, Wang, Sinan, Sun, Bingxia, Cui, Yuting, Gao, Qingzhi, and Sang, Feng
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PROTEIN-tyrosine kinases , *KINASE inhibitors , *CANCER cells , *PROTEOLYSIS , *PHASE transitions - Abstract
Eleven new proteolysis targeting chimeras (PROTACs) based on promiscuous kinase inhibitor Sunitinib were designed, synthesized, and assessed for their anticancer activity against four human cancer cell lines A498, K562, HL‐60 and MCF‐7. Two known compounds were also prepared and used as control samples. The CCK‐8 assay results showed that a new PROTAC with a 1,4‐diaminobutane linker (PROTAC 10) exhibited significant antiproliferative activity against A498 (IC50=0.11 ± 0.01 μM) and K562 (IC50=0.59 ± 0.21 μM) cell lines. Western blot analysis showed that in addition to the previously reported G1 to S phase transition 1 (GSPT1), PROTAC 10 also reduced the protein level of fms‐like tyrosine kinase 3 (FLT3) and proto‐oncogene tyrosine protein kinase Src (SRC) in A498 cells. Moreover, PROTAC 10 regulated the protein levels of GSPT1 and SRC in a dose‐ and time‐dependent manner and induced degradation of GSPT1 in a ubiquitin‐proteasome‐dependent manner in K562 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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8. Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells.
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Lovison, Denise, Alessi, Dario, Allegri, Lorenzo, Baldan, Federica, Ballico, Maurizio, Damante, Giuseppe, Galasso, Marilisa, Guardavaccaro, Daniele, Ruggieri, Silvia, Melchior, Andrea, Veclani, Daniele, Nardon, Chiara, and Baratta, Walter
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ANAPLASTIC thyroid cancer , *RUTHENIUM , *CANCER cells , *DIPHOSPHINE , *CELL lines , *RUTHENIUM compounds - Abstract
The chiral cationic complex [Ru(η1‐OAc)(CO)((R,R)‐Skewphos)(phen)]OAc (2R), isolated from reaction of [Ru(η1‐OAc)(η2‐OAc)(R,R)‐Skewphos)(CO)] (1R) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)‐Skewphos)(phen)]Y (X=Y=OPiv 3R; X=SAc, Y=OAc 4R). The corresponding enantiomers 2S‐4S have been obtained from 1S containing (S,S)‐Skewphos. Reaction of 2R and 2S with (S)‐cysteine and NaPF6 at pH=9 gives the diastereoisomers [Ru((S)‐Cys)(CO)(PP)(phen)]PF6 (PP=(R,R)‐Skewphos 2R‐Cys; (S,S)‐Skewphos 2S‐Cys). The DFT energetic profile for 2R with (S)‐cysteine in H2O indicates that aquo and hydroxo species are involved in formation of 2R‐Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n‐octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT‐116 and A549 cell lines with EC50 values of 2.8–0.04 μM. The (R,R)‐Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4R (EC50=0.04 μM) being 14 times more cytotoxic than 4S against the anaplastic thyroid cancer 8505 C cell line. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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9. Design, synthesis, and biological evaluation of RSL3-based GPX4 degraders with hydrophobic tags.
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Ning, Yao, Zhu, Zeqi, Wang, Yicheng, Fan, Xuejing, Wang, Jing, Qian, Huimei, Qiu, Xue, and Wang, Yong
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APOPTOSIS , *PROTEOLYSIS , *UBIQUITIN , *CANCER cells , *ANTINEOPLASTIC agents - Abstract
Ferroptosis is a new type of programmed cell death characterized by iron-dependent lipid peroxidation, during which glutathione peroxidase 4 (GPX4) plays an essential role and is well-recognized as a promising therapeutic target for cancer treatment. Although some GPX4 degradation molecules have been developed to induce ferroptosis, the discovery of GPX4 degraders with hydrophobic tagging (HyT) as an innovative approach is more challenging. Herein, we designed and synthesized a series of HyT degraders by linking the GPX4 inhibitor RSL3 with a hydrophobic and bulky group of adamantane. Among them, compound R8 is a potent degrader (DC 50 , 24h = 0.019 μM) which can effectively degrade GPX4 in a dose- and time-dependent manner. Furthermore, compound R8 exhibited superior in vitro antitumor potency against HT1080 and MDA-MB-231 cell lines with IC 50 values of 24 nM and 32 nM respectively, which are 4 times more potent than parental compound RSL3. Mechanistic investigation evidenced that R8 consumes GPX4 protein mainly through the ubiquitin proteasome (UPS) and enables to induce the accumulation of LPO, thereby triggering ferroptosis. Our work presented the novel GPX4 degrader of R8 by HyT strategy, and provided a promising pathway of degradation agents for the treatment of ferroptosis relevant diseases. [Display omitted] • The synthesis and SAR analysis of varieties of GPX4 degraders with hydrophobic tags were performed. • Compound R8 with flexible alkane chain showed remarkable protein degradation activity with a DC 50 value at nanomolar level. • R8 induced a strong ferroptotic death on multiple cancer cells evidenced by LPO flow cytometry. • R8 could decrease GPX4 protein mainly through the ubiquitin proteasome. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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10. Synthesis and Evaluation of Novel Carboxamides Capable of Causing Centrosome Declustering and Apoptosis in Breast Cancer Cells.
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Farrukh, Usama B., Bilal, Aishah, Zahid, Huda, Iqbal, Maheen, Manzoor, Safia, Firdous, Farhat, Furqan, Muhammad, Azeem, Muhammad, Emwas, Abdul‐Hamid, Alazmi, Meshari, Gao, Xin, Saleem, Rahman S. Z., and Faisal, Amir
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BREAST cancer , *CARBOXAMIDES , *APOPTOSIS , *CANCER cells , *CELL death , *CENTROSOMES , *MITOSIS - Abstract
The fragility of cancer cells at the time of mitosis has served as an important target for the development of many successful chemotherapeutic agents. Many cancers cells have supernumerary centrosomes that they cluster during mitosis to form bipolar spindles. Inhibition of centrosome clustering in these cells results in multipolar spindle formation and apoptotic cell death, providing an opportunity to selectively target a subset of cancers with centrosome amplification. In the current work, we report synthesis of 29 novel tethered biaryls and biological evaluation of their ability to inhibit centrosome clustering in breast cancer cells (BT‐549). We have identified N‐benzhydryl‐5‐nitrofuran‐2‐carboxamide (5 h) as a centrosome declustering compound. 5 h has potent antiproliferative activity in centrosome amplified BT‐549 cells with GI50 value of 1.81±0.19 μM (n=2). Treatment of BT‐549 cells with 5 h causes centrosome declustering resulting in mitotic arrest due to multipolar spindle formation and misaligned chromosomes which ultimately leads to apoptotic cell death. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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11. 19F NMR Allows the Investigation of the Fate of Platinum(IV) Prodrugs in Physiological Conditions.
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Yuan, Siming, Zhu, Yang, Dai, Yi, Wang, Yu, Jin, Duo, Liu, Manman, Tang, Liqin, Arnesano, Fabio, Natile, Giovanni, and Liu, Yangzhong
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PRODRUGS , *PLATINUM , *CANCER cells , *REDUCING agents - Abstract
PtIV prodrugs can overcome resistance and side effects of conventional PtII anticancer therapies. By 19F‐labeling of a PtIV prodrug (Pt‐FBA, FBA=p‐fluorobenzoate), the activation under physiological conditions could be investigated. Unlike single‐electron reductants, multi‐electron agents can efficiently promote the two electrons reduction of PtIV to PtII. The activation of Pt‐FBA in cell lysate is highly dependent upon the type of cancer cells. When administered to E. coli, Pt‐FBA is reduced intracellularly and free FBA can shuttle out of the cell. The reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of ZnII ions. When injected into mice, Pt‐FBA undergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless, unreduced Pt‐FBA can accumulate to detectable levels in liver and kidneys. The 19F NMR approach has the advantage of avoiding the interference of all background signals. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Synthesis of Thiazole Linked Imidazo[2,1-b]Thiazoles as Anticancer Agents.
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Mahmoud, Huda K., Gomha, Sobhi M., Farghaly, Thoraya A., and Awad, Hanem M.
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ANTINEOPLASTIC agents , *THIAZOLES , *DRUG derivatives , *DIOXANE , *CANCER cells , *THIOSEMICARBAZONES - Abstract
Based on the search for new heterocyclic drugs suitable as anticancer agents and our knowledge of the efficacy of thiazol and imidazothiazole derivatives as anticancer drugs, we have created four new series of thiazolylimidazothiazole derivatives from the reaction of each of imidazothiazole-thiosemicabazone and imidazothiazole-thicarbohydrazone derivatives with acetyl-hydrazonoyl chlorides and ester-hydrazonoyl chlorides in dioxane/drops of Et3N. The structure of the four novel series of thiazolylimidazothiazoles was characterized by physical and spectroscopic tools. In addition, all the newly synthesized derivatives were examined in vitro for their activity against HCT-116 and MCF-7 human cancer cells using the MTT assay to evaluate their pharmaceutical importance. The encouraging potent results observed from anticancer elusidation studies on the newly prepared thiazolylimidazothiazole derivatives make the design and synthesis of novel series of these systems and studying of their pharmaceutical importance an active zone for more and more investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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13. In‐Cell Generation of Anticancer Phenanthridine Through Bioorthogonal Cyclization in Antitumor Prodrug Development.
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Maslah, Hichem, Skarbek, Charles, Gourson, Catherine, Plamont, Marie‐Aude, Pethe, Stéphanie, Jullien, Ludovic, Le Saux, Thomas, and Labruère, Raphaël
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PHENANTHRIDINE , *RING formation (Chemistry) , *REACTIVE oxygen species , *ANTINEOPLASTIC agents , *BORONIC esters , *CANCER cells - Abstract
Pharmacological inactivation of antitumor drugs toward healthy cells is a critical factor in prodrug development. Typically, pharmaceutical chemists graft temporary moieties to existing antitumor drugs to reduce their pharmacological activity. Here, we report a platform able to generate the cytotoxic agent by intramolecular cyclization. Using phenanthridines as cytotoxic model compounds, we designed ring‐opened biaryl precursors that generated the phenanthridines through bioorthogonal irreversible imination. This reaction was triggered by reactive oxygen species, commonly overproduced in cancer cells, able to convert a vinyl boronate ester function into a ketone that subsequently reacted with a pendant aniline. An inactive precursor was shown to engender a cytotoxic phenanthridine against KB cancer cells. Moreover, the kinetic of cyclization of this prodrug was extremely rapid inside living cells of KB cancer spheroids so as to circumvent drug action. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Hypoxia‐Responsive Gene Editing to Reduce Tumor Thermal Tolerance for Mild‐Photothermal Therapy.
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Li, Xueqing, Pan, Yongchun, Chen, Chao, Gao, Yanfeng, Liu, Xinli, Yang, Kaiyong, Luan, Xiaowei, Zhou, Dongtao, Zeng, Fei, Han, Xin, and Song, Yujun
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THERMAL tolerance (Physiology) , *CRISPRS , *TUMOR microenvironment , *HIGH temperatures , *REDUCTASES , *CANCER cells , *GENOME editing , *THERMAL resistance - Abstract
Near‐infrared (NIR)‐light‐triggered photothermal therapy (PTT) is usually associated with undesirable damage to healthy organs nearby due to the high temperatures (>50 °C) available for tumor ablation. Low‐temperature PTT would therefore have tremendous value for clinical application. Here, we construct a hypoxia‐responsive gold nanorods (AuNRs)‐based nanocomposite of CRISPR‐Cas9 for mild‐photothermal therapy via tumor‐targeted gene editing. AuNRs are modified with azobenzene‐4,4′‐dicarboxylic acid (p‐AZO) to achieve on‐demand release of CRISPR‐Cas9 using hypoxia‐responsive azo bonds. In the hypoxic tumor microenvironment, the azo groups of the hypoxia‐activated CRISPR‐Cas9 nanosystem based on gold nanorods (APACPs) are selectively reduced by the overexpression of reductases, leading to the release of Cas9 and subsequent gene editing. Owing to the knockout of HSP90α for reducing the thermal resistance of cancer cells, highly effective tumor ablation both in vitro and in vivo was achieved with APACPs under mild PTT. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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15. Novel Anthracycline Utorubicin for Cancer Therapy.
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Simón‐Gracia, Lorena, Sidorenko, Valeria, Uustare, Ain, Ogibalov, Ivan, Tasa, Andrus, Tshubrik, Olga, and Teesalu, Tambet
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CANCER treatment , *CANCER cells , *THERAPEUTICS , *BREAST tumors , *CELL lines , *POLYMERSOMES , *DOXORUBICIN - Abstract
Novel anticancer compounds and their precision delivery systems are actively developed to create potent and well‐tolerated anticancer therapeutics. Here, we report the synthesis of a novel anthracycline, Utorubicin (UTO), and its preclinical development as an anticancer payload for nanocarriers. Free UTO was significantly more toxic to cultured tumor cell lines than the clinically used anthracycline, doxorubicin. Nanoformulated UTO, encapsulated in polymeric nanovesicles (polymersomes, PS), reduced the viability of cultured malignant cells and this effect was potentiated by functionalization with a tumor‐penetrating peptide (TPP). Systemic peptide‐guided PS showed preferential accumulation in triple‐negative breast tumor xenografts implanted in mice. At the same systemic UTO dose, the highest UTO accumulation in tumor tissue was seen for the TPP‐targeted PS, followed by nontargeted PS, and free doxorubicin. Our study suggests potential applications for UTO in the treatment of malignant diseases and encourages further preclinical and clinical studies on UTO as a nanocarrier payload for precision cancer therapy. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Tunable Anticancer Activity of Furoylthiourea‐Based RuII–Arene Complexes and Their Mechanism of Action.
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Swaminathan, Srividya, Haribabu, Jebiti, Kalagatur, Naveen Kumar, Nikhil, Maroli, Balakrishnan, Nithya, Bhuvanesh, Nattamai S. P., Kadirvelu, Krishna, Kolandaivel, Ponmalai, and Karvembu, Ramasamy
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VASCULAR endothelial growth factor receptors , *RUTHENIUM compounds , *STRUCTURE-activity relationships , *ELECTRIC potential , *CANCER cells , *POLAR effects (Chemistry) - Abstract
Fourteen new RuII–arene (p‐cymene/benzene) complexes (C1–C14) have been synthesized by varying the N‐terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure–activity relationships of the Ru–p‐cymene and Ru–benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR‐32 cancer cells, with C5 (Ru–p‐cymene complex containing C6H2(CH3)3 as N‐terminal substituent) and C13 (Ru–benzene complex containing C6H4(CF3) as N‐terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim‐1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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17. Organoselenium with electrophilic center targeting PDGFB for selective osteosarcoma radiosensitization.
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Tian, Yuan, Zhu, An, Huang, Wei, Shi, Sujiang, and Chen, Tianfeng
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PLATELET-derived growth factor , *OSTEOSARCOMA , *RADIATION-sensitizing agents , *SELENOPROTEINS , *PROTEIN kinases , *CANCER cells - Abstract
Herein we demonstrate a new strategy by introducing Se atom with strong polarization effects to obtain highly bioactive organoselenium with electrophilic center. Organoselenium interact with Cys16 and Thr18 of PDGFB in malignant osteosarcoma MG63 cells through non-covalent bond, which further block the activation of intracellular AKT/JNK and downstream signaling pathways to promote cancer cells apoptosis. [Display omitted] • Organic selenium with high bioactivity electrophilic center was synthesized. • Org-Se can target PDGFB protein in MG63 cells and promote apoptosis. • Org-Se combined with radiotherapy can promote apoptosis of MG63 cells. Growth factor-like proteins play an important role in promoting oncogenesis. Therefore, designing specific inhibitors of such targets would facilitate the development of targeted drugs with low toxicity. However, low affinity and poor specificity between drugs and target proteins always affect the selectivity and action efficacy. Herein we demonstrates a new strategy by introducing selenium (Se) atom with strong polarization effects to obtain highly bioactive organoselenium with electrophilic center. The results of target-capturing analysis reveals that organoselenium interact with Cys16 and Thr18 of the platelet-derived growth factor B (PDGFB) protein in malignant osteosarcoma MG63 cells through non-covalent bond, thus inhibiting the expression and activity of PDGFB, which further block the activation of intracellular protein kinase B/c-Jun N-terminal kinases (AKT/JNK) and downstream signaling pathways to promote cancer cells apoptosis. Taken together, we have developed a novel strategy by introducing Se-based electrophilic centers for the development of targeted therapeutic agents for malignant tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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18. In-Silico-Inspired Design of 1,3-Diynyl Congeners of Noscapine as Promising Tubulin-Binding Anticancer Agent: Chemical Synthesis and Cellular Activity with Breast Cancer Cell Lines.
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Pragyandipta, Pratyush, Meher, Rajesh K., Naik, Manas R., Nagireddy, Praveen K. R., Pedapati, Ravi K, Kantevari, Srinivas, and Naik, Pradeep K.
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CHEMICAL synthesis , *BREAST cancer , *CELL lines , *ANTINEOPLASTIC agents , *CANCER cells - Abstract
A panel of 1,3-diynyl-noscapinoids (20–22) were strategically designed to increase the anticancer activity of the lead molecule, noscapine. Structure-activity analyses revealed strong predicted free energy of binding (ΔGbind,pred) of 6.694, 7.294 and 7.468 kcal/mol, for 20–22 respectively compared to noscapine (experimental free energy of binding (ΔGbind,expt) is 5.246 kcal/mol). These novel derivatives were demonstrated to bind tubulin by fluorescence quenching assay and Far-UV circular dichroism. Further, they were tested to exhibit potent cytotoxic activity compared to noscapine using two human breast cancer cell lines. The IC50 value for noscapine, 20, 21 and 22 has been derived to be 35.2, 27.3, 18.7 and 12.7 μM using MCF7 and 39.6, 31.4, 22.5 and 16.1 μM using MDAMB-231. These derivatives were found to arrest cell cycle in the G2/Mphase followed by apoptosis and appearance of TUNEL-positive cells. Thus, we conclude that 1,3-diynyl derivatives of noscapine have great potential to be a novel therapeutic agent for breast cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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19. Discovery of a Chiral DNA‐Targeted Platinum–Acridine Agent with Potent Enantioselective Anticancer Activity.
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Zhang, Shenjie, Yao, Xiyuan, Watkins, Noah H., Rose, P. Keegan, Caruso, Sofia R., Day, Cynthia S., and Bierbach, Ulrich
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NON-small-cell lung carcinoma , *DNA adducts , *LIGAND analysis , *LUNG cancer , *STRUCTURE-activity relationships , *CANCER cells - Abstract
A structure–activity relationship study was performed for a set of rigidified platinum–acridine anticancer agents containing linkers derived from chiral pyrrolidine and piperidine scaffolds. Screening a library of microscale reactions and selected resynthesized compounds in non‐small‐cell lung cancer (NSCLC) cells showed that cytotoxicities varied by more than three orders of magnitude. A potent hit compound was discovered containing a (R)‐N‐(piperidin‐3‐yl) linker (P2‐6R), which killed NCI‐H460 and A549 lung cancer cells 100 times more effectively than the S enantiomer (P2‐6S). P2‐6R accumulated in A549 cells significantly faster and produced 50‐fold higher DNA adduct levels than P2‐6S. Ligand similarity analysis suggests that only module 6R may be compatible with strainless monofunctional intercalative binding. NCI‐60 screening and COMPARE analysis highlights the spectrum of activity and potential utility of P2‐6R for treating NSCLC and other solid tumors. [ABSTRACT FROM AUTHOR]
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- 2020
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20. PlatinER: A Highly Potent Anticancer Platinum(II) Complex that Induces Endoplasmic Reticulum Stress Driven Immunogenic Cell Death.
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Tham, Max Jing Rui, Babak, Maria V., and Ang, Wee Han
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CELL death , *REACTIVE oxygen species , *ENDOPLASMIC reticulum , *PHAGOCYTOSIS , *PLATINUM , *CANCER cells - Abstract
Immunogenic cell death (ICD) is a rare immunostimulatory form of cell death that can improve the clinical outcomes of chemo‐immunotherapeutic combination regimens through the establishment of a long‐term cancer immunity. None of the clinically used DNA‐binding PtII complexes is considered a Type II ICD inducer. We generated a series of PtII‐carbene complexes by applying minor structural alterations to the scaffold of a Type II ICD inducer Pt‐NHC and compared their efficiency in triggering ICD‐related cellular responses and phagocytosis. We successfully identified PlatinER, a novel highly potent PtII candidate with superior ICD properties. Crucially, the magnitude of ICD‐associated phagocytosis induced upon exposure of cancer cells to Pt complexes was dependent on the levels of ER‐localized reactive oxygen species (ROS) generation, which underpins their mechanisms of action and provides a feasible approach for the design of more effective Type II ICD inducers. [ABSTRACT FROM AUTHOR]
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- 2020
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21. Pincer‐Based Heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III), and Pt(II)/Cu(I) Complexes: Synthesis and Evaluation of Antiproliferative Properties.
- Author
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Bertrand, Benoît, Gontard, Geoffrey, Botuha, Candice, and Salmain, Michèle
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PLATINUM , *TRIPLE-negative breast cancer , *HETEROBIMETALLIC complexes , *RUTHENIUM compounds , *METAL complexes , *CELL lines , *CANCER cells - Abstract
Platinum pincer‐based complexes [(O^N^O)Pt(L)] (L = DMSO, pyridine, triphenylphosphine or 1,3‐dimethylbenzimidazol‐2‐ylidene) carrying an (N^N) coordination site were used as starting materials to synthesize a series of seven cationic heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III), and Pt(II)/Cu(I) presenting a [(p‐cymene)RuCl]+, a [(Cp*)IrCl]+ (Cp* = η5‐pentamethylcyclopentadienyl), and a [(NHCiPr)Cu]+ {NHCiPr = 1,3‐bis(2,6‐diisopropylphenyl)imidazole‐2‐ylidene} moiety, respectively. The X‐ray structure of one of the bimetallic Pt(II)/Ir(III) complexes showed a distortion of the organic platform to accommodate the coordination geometry of both metal centers, as already observed for previous Pt(II)/Re(I) complexes. The antiproliferative activity of the complexes was first screened on the triple negative breast cancer cell line MDA‐MB‐231. Then the IC50 of the most active candidates was determined on a wider panel of human cancer cells (MDA‐MB‐231, MCF‐7 and A2780) as well as on a non‐tumorigenic cell line (MCF‐10A). The most toxic compound, namely the Pt(II)/Cu(I) heterobimetallic complex 4c, showed antiproliferative activity down to the nanomolar level. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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22. Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo.
- Author
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Song, Hualong, Allison, Simon J., Brabec, Viktor, Bridgewater, Hannah E., Kasparkova, Jana, Kostrhunova, Hana, Novohradsky, Vojtech, Phillips, Roger M., Pracharova, Jitka, Rogers, Nicola J., Shepherd, Samantha L., and Scott, Peter
- Subjects
- *
TUMORS , *COLON cancer , *GLUCOSE , *CELL lines , *CANCER cells - Abstract
Monosaccharides are added to the hydrophilic face of a self‐assembled asymmetric FeII metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water‐stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53+/+) with respect to the non‐cancerous ARPE‐19 cell line. While the most selective compound is a glucose‐appended enantiomer, its cellular entry is not mainly glucose transporter‐mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5‐fold, and a non‐destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d; performance as good as cisplatin but with the advantage of no weight loss in the subjects. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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23. Stiff‐Stilbene Ligands Target G‐Quadruplex DNA and Exhibit Selective Anticancer and Antiparasitic Activity.
- Author
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O'Hagan, Michael P., Peñalver, Pablo, Gibson, Rosina S. L., Morales, Juan C., and Galan, M. Carmen
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MOLECULAR shapes , *LIGANDS (Chemistry) , *HELA cells , *MOLECULAR recognition , *CANCER cells , *DNA , *QUADRUPLEX nucleic acids - Abstract
G‐quadruplex nucleic acid structures have long been studied as anticancer targets whilst their potential in antiparasitic therapy has only recently been recognized and barely explored. Herein, we report the synthesis, biophysical characterization, and in vitro screening of a series of stiff‐stilbene G4 binding ligands featuring different electronics, side‐chain chemistries, and molecular geometries. The ligands display selectivity for G4 DNA over duplex DNA and exhibit nanomolar toxicity against Trypasanoma brucei and HeLa cancer cells whilst remaining up to two orders of magnitude less toxic to non‐tumoral mammalian cell line MRC‐5. Our study demonstrates that stiff‐stilbenes show exciting potential as the basis of selective anticancer and antiparasitic therapies. To achieve the most efficient G4 recognition the scaffold must possess the optimal electronics, substitution pattern and correct molecular configuration. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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24. Development of Glucose Transporter (GLUT) Inhibitors.
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Reckzeh, Elena S. and Waldmann, Herbert
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GLUCOSE transporters , *GLYCOLYSIS , *GLUCOSE metabolism , *CHEMICAL biology , *PHARMACEUTICAL chemistry , *CANCER cells - Abstract
The discovery of novel compound classes endowed with biological activity is at the heart of chemical biology and medicinal chemistry research. This enables novel biological insights and inspires new approaches to the treatment of diseases. Cancer cells frequently exhibit altered glycolysis and glucose metabolism and an increased glucose demand. Thus, targeting glucose uptake and metabolism may open up novel opportunities for the discovery of compounds that differentiate between normal and malignant cells. This review discusses the different chemical approaches to the development of novel inhibitors of glucose uptake through facilitative glucose transporters (GLUTs), and focusses on the most advanced and potent inhibitor classes known to date. GLUT inhibitors may find application not only in the treatment of cancer, but also of other proliferative diseases that exhibit glucose addiction. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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25. Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents.
- Author
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Arafa, Wael Abdelgayd Ahmed and Hussein, Modather F.
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DENSITY functional theory , *STRUCTURE-activity relationships , *CELL lines , *ANTINEOPLASTIC agents , *CANCER cells - Abstract
Summary of main observation and conclusion: A highly efficient, simple, and clean single‐step sonosynthetic procedure has been sophisticated for assembling new series of mono‐ and bis‐pyridine dicarbonitriles from ketones, HCl, and tetracyanoethylene. The presented protocol is applicable for the preparation of a broad range of uniquely substituted pyridine dicarbonitriles and seems to be superior in comparison with other previously reported methods. The antiproliferative impact of the newly synthesized derivatives was screened towards three representative cancer cell lines (MCF‐7, A549, and HCT116). Most of the evaluated derivatives showed a moderate to excellent anti‐proliferative activity towards the selected cell lines. Of these, compounds 4h, 4k, 10, 12a, and 12b showed both potent anticancer activity (IC50<10 μM) and lower cytotoxic effect (IC50 > 58 μM) on non‐tumorigenic cells (MCF‐10A and NCM460), suggesting their promising potential to be lead molecules for future antitumor drug discovery. The structure‐activity relationships have been also discussed. Moreover, quantum chemical studies based on Density Functional Theory (DFT) of the synthesized compounds were investigated and found to be consistent with the in vitro inhibitory activities. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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26. Ligand‐Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes.
- Author
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Zhang, Wen‐Ying, Bridgewater, Hannah E., Banerjee, Samya, Soldevila‐Barreda, Joan J., Clarkson, Guy J., Shi, Huayun, Imberti, Cinzia, and Sadler, Peter J.
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RHODIUM compounds , *RHODIUM , *NAD (Coenzyme) , *REACTIVE oxygen species , *AQUEOUS solutions , *CANCER cells , *OVARIAN cancer - Abstract
We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [CpXRh(C^N)Z]0/+, in which CpX = Cp*, Cpph, or Cpbiph, C^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X‐ray crystal structures showing the expected "piano‐stool" configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9‐ethyl guanine or glutathione compared to their pyridine analogues. The 1‐biphenyl‐2,3,4,5‐tetramethylcyclopentadienyl complex [CpbiphRh(benzo‐[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD+ and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [CpbiphRh(benzo[h]quinoline)py]+ (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5‐fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand‐controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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27. Rh(III)‐Catalyzed Redox‐Neutral [4+2] Annulation for Direct Assembly of 3‐Acyl Isoquinolin‐1(2H)‐ones as Potent Antitumor Agents.
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Bian, Mengyao, Ma, Lei, Wu, Min, Wu, Liexin, Gao, Hui, Yi, Wei, Zhang, Chao, and Zhou, Zhi
- Subjects
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ANTINEOPLASTIC agents , *ANNULATION , *CANCER cells , *QUINAZOLINONES , *RHODIUM , *RING-opening reactions , *LUNG cancer - Abstract
By virtue of an efficient rhodium(III)‐catalyzed redox‐neutral C−H activation/ring‐opening of a strained ring/[4+2] annulation cascade of N‐methoxybenzamides with propargyl cycloalkanols, diverse 3‐acyl isoquinolin‐1(2H)‐ones were directly obtained in good yields and with excellent functional group compatibility. Additionally, their antitumor activities against various human cancer cells including HepG2, A549, MCF‐7 and SH‐SY5Y were evaluated and the action mechanism of the selected compound was also investigated in vitro. The results revealed that these products possessed a potent efficacy, by inhibiting proliferation and inducing apoptosis in a time‐dependent and dose‐dependent manner, suggesting that such compounds can serve as promising candidates for anti lung cancer drug discovery. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. Platinum (IV) Derivatives with Cinnamate Axial Ligands as Potent Agents Against Both Differentiated and Tumorigenic Cancer Stem Rhabdomyosarcoma Cells.
- Author
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Zajac, Juraj, Novohradsky, Vojtech, Markova, Lenka, Brabec, Viktor, and Kasparkova, Jana
- Subjects
- *
CANCER stem cells , *PLATINUM , *LIGANDS (Chemistry) , *CINNAMIC acid , *ORGANOPLATINUM compounds , *CANCER cells , *DRUG design - Abstract
To design an anticancer drug capable of inhibiting not only the proliferation of the differentiated tumor cells but also reducing the tumorigenic capability of cancer stem cells (CSCs), the new PtIV prodrugs with axial cinnamate ligands were synthesized. We demonstrate their superior antiproliferative activity in monolayer and 3D spheroid antiproliferative activity tests using panel of cancer cell lines. An outstanding activity was found against rhabdomyosarcoma cells, one of the most problematic and poorly treatable pediatric tumors. The results also suggest that the released PtII compound inhibits antiproliferative activity of cancer cells by DNA‐damage mediated mechanism; the released cinnamic acid can trigger processes leading to differentiation, making the CSCs more sensitive to killing by the platinum part of the complex. PtIV complex with axial cinnamate ligands is the first PtIV prodrug capable of overcoming CSCs resistance and induce death in both CSCs and bulk cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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29. Gold-catalyzed cyclization in the synthesis of antimitotic 2,3-dihydrobenzo[b]oxepine derivatives of colchicine.
- Author
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Bukhvalova, S. Yu., Maleev, A. A., Gracheva, Yu. A., Voitovich, Yu. V., Ignatov, S. K., Svirshchevskaya, E. V., and Fedorov, A. Yu.
- Subjects
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CELL lines , *CANCER cells , *ANTINEOPLASTIC agents - Abstract
New allocolchicine derivatives bearing 2,3-dihydrobenzo[b]oxepine moiety were synthesized via gold-catalyzed cyclization as a key synthetic step. The obtained 2,3-dihydrobenzo[b]oxepine-containing allocolchicinoids possess cytotoxic activity against HEK293, PANC-1, COL0357, HeLa, and Colon26 cancer cell lines at low micromolar range of concentrations. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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30. Potent and Selective Cytotoxic and Anti‐inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands.
- Author
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Reddy, T. Srinivasa, Pooja, Deep, Privér, Steven H., Luwor, Rodney B., Mirzadeh, Nedaossadat, Ramesan, Shwathy, Ramakrishna, Sistla, Karri, Shailaja, Kuncha, Madhusudana, and Bhargava, Suresh K.
- Subjects
- *
LIGANDS (Chemistry) , *PHOSPHINE , *SULFIDES , *TUMOR growth , *CANCER cells , *CISPLATIN - Abstract
Four cycloaurated phosphine sulfide complexes, [Au{κ2‐2‐C6H4P(S)Ph2}2][AuX2] [X=Cl (2), Br (3), I (4)] and [Au{κ2‐2‐C6H4P(S)Ph2}2]PF6 (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological‐like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showed that treatment with compounds 4 and 5 resulted in significant inhibition of tumor growth (35.8 and 46.9 %, respectively), better than that of cisplatin (29 %). The newly synthesized gold complexes were also evaluated for their in vitro and in vivo anti‐inflammatory activity through the study of lipopolysaccharide (LPS)‐activated macrophages and carrageenan‐induced hind paw edema in rats, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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31. Front Cover: 5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity (ChemPlusChem 12/2023).
- Author
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Rodríguez‐Arce, Esteban, Gavrilov, Eric, Alvite, Ximena, Nayeem, Nazia, León, Ignacio E., Neary, Michelle C., Otero, Lucía, Gambino, Dinorah, Olea Azar, Claudio, and Contel, María
- Subjects
- *
ANTINEOPLASTIC agents , *GOLD , *CANCER cells , *PHARMACEUTICAL chemistry , *THIOSEMICARBAZONES - Abstract
This article, published in ChemPlusChem, discusses the synthesis, stability studies, and anticancer activity of 5-Nitrofuryl-Containing Thiosemicarbazone Gold(I) Compounds. The article refers to these compounds as "Supergold," a gender-neutral warrior with superpowers that fights against cancer. The golden armor and sword of Supergold symbolize the pharmacological power of the gold atom, while the gold-thiosemicarbazones molecules engraved on the shield represent the warrior's coat of arms. Supergold selectively destroys different cancer cells. The article provides more information on this topic and is authored by Esteban Rodríguez‐Arce, María Contel, and their colleagues. [Extracted from the article]
- Published
- 2023
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32. Antiadhesive Nanosomes Facilitate Targeting of the Lysosomal GlcNAc Salvage Pathway through Derailed Cancer Endocytosis.
- Author
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Koide, Ryosuke and Nishimura, Shin‐Ichiro
- Subjects
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NANOMEDICINE , *ENDOCYTOSIS , *URIDINE diphosphate , *WASTE salvage , *GLYCOSIDASES , *CANCER cells , *LYSOSOMES , *MACROMOLECULES - Abstract
Activated endocytosis of extracellular macromolecules and their intracellular trafficking to lysosomes is an essential metabolic mechanism in cancer cells during their rapid proliferation. Cancer cells reuse a vast amount of N‐acetylglucosamine (GlcNAc) supplied from the GlcNAc salvage pathway for the accelerated synthesis of a pivotal uridine diphosphate (UDP)‐GlcNAc. A method to inactivate key glycosidases in lysosomes could critically contribute to the development of potent anticancer therapy. Here we demonstrate that "nanosomes" made of core metals covered by an antiadhesive mixed self‐assembled monolayer allow for avoiding nonspecific surface protein corona and targeted molecular delivery through activated endocytosis. Nanosomes carrying suicide substrates showed that lysosomal glycosidases such as β‐hexosaminidase and β‐galactosidase in cancer cells are promising targets for novel anticancer therapeutic nanomedicine that induce apoptotic cell death through lysosomal membrane permeabilization. The advantage of this method is evident because multivalent surface loading by antiadhesive nanosomes makes it possible to highlight "weak interactions" such as carbohydrate–lectin interactions independent of surface protein corona. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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33. Polymeric Encapsulation of Novel Homoleptic Bis(dipyrrinato) Zinc(II) Complexes with Long Lifetimes for Applications as Photodynamic Therapy Photosensitisers.
- Author
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Karges, Johannes, Basu, Uttara, Blacque, Olivier, Chao, Hui, and Gasser, Gilles
- Subjects
- *
PHOTODYNAMIC therapy , *REACTIVE oxygen species , *ZINC , *EXCITED states , *LEAD compounds , *CANCER cells , *ULTRACOLD molecules - Abstract
The use of photodynamic therapy (PDT) to treat cancer has received increasing attention over the last years. However, the clinically used photosensitisers (PSs) have some limitations that include poor aqueous solubility, hepatotoxicity, photobleaching, aggregation, and slow clearance from the body, so the design of new classes of PSs is of great interest. We present the use of bis(dipyrrinato)zinc(II) complexes with exceptionally long lifetimes as efficient PDT PSs. Based on the heavy‐atom effect, intersystem crossing of these complexes changes the excited state from singlet to a triplet state, thereby enabling singlet oxygen generation. To overcome the limitation of quenching effects in water and improve water solubility, the lead compound 3 was encapsulated in a polymer matrix. It showed impressive phototoxicity upon irradiation at 500 nm in various monolayer cancer cells as well as 3D multicellular tumour spheroids, without observed dark toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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34. A Triangular Platinum(II) Multinuclear Complex with Cytotoxicity Towards Breast Cancer Stem Cells.
- Author
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Eskandari, Arvin, Kundu, Arunangshu, Ghosh, Sushobhan, and Suntharalingam, Kogularamanan
- Subjects
- *
PLATINUM , *BREAST cancer , *CANCER stem cells , *DNA damage , *ANTINEOPLASTIC agents , *CANCER cells - Abstract
The preparation of multinuclear metal complexes offers a route to novel anticancer agents and delivery systems. The potency of a novel triangular multinuclear complex containing three platinum atoms, Pt‐3, towards breast cancer stem cells (CSCs) is reported. The trinuclear platinum(II) complex, Pt‐3 exhibits selective toxicity towards breast CSCs over bulk breast cancer cells and non‐tumorigenic breast cells. Remarkably, Pt‐3 inhibits the formation, size, and viability of mammospheres to a better extent than salinomycin, an established CSC‐potent agent, and cisplatin and carboplatin, clinically used platinum drugs. Mechanism of action studies show that Pt‐3 effectively enters breast CSCs, penetrates the nucleus, induces genomic DNA damage, and prompts caspase‐dependent apoptosis. To the best of our knowledge, Pt‐3 is the first multinuclear platinum complex to selectively kill breast CSCs over other breast cell types. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
35. Design and Synthesis of 2‐(5‐Phenylindol‐3‐yl)benzimidazole Derivatives with Antiproliferative Effects towards Triple‐Negative Breast Cancer Cells by Activation of ROS‐Mediated Mitochondria Dysfunction.
- Author
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Wang, Mengying, Wu, Yusheng, Xu, Cuifang, Zhao, Rucheng, Huang, Yanyu, Zeng, Xiangchao, and Chen, Tianfeng
- Subjects
- *
BENZIMIDAZOLES , *TRIPLE-negative breast cancer , *BENZIMIDAZOLE derivatives , *CANCER cells , *MITOCHONDRIA - Abstract
Benzimidazole derivatives are widely studied because of their broad‐spectrum biological activity, such as antitumor properties and excellent fluorescence performance. Herein, two types of 2‐(5‐phenylindol‐3‐yl)benzimidazole derivatives (1 a–1 h and 2 a–2 e) were rationally designed and synthesized. When these compounds were investigated in vitro anti‐screening assays, we found that all of them possessed antitumor effect, in particular compound 1 b, which showed an outstanding antiproliferative effect on MDA‐MB‐231 cells (IC50≈2.6 μm). A study of the drug action mechanisms in cells showed that the antitumor activity of the compounds is proportional to their lipophilicity and cellular uptake; the tested compounds all entered the lysosome of MDA‐MB‐231 cells and caused changes in the levels of reactive oxygen species (ROS), and then caused mitochondrial damage. Apparent differences in the ROS levels for each compound suggest that the lethality of these compounds towards MDA‐MB‐231 cells is closely related to the ROS levels. Taken together, this study not only provides a theoretical basis for 2‐(5‐phenylindol‐3‐yl)benzimidazole anticarcinogens but also offers new thinking on the rational design of next‐generation antitumor benzimidazole derivatives. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
36. Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion‐Targeted Platinum(II) Complex.
- Author
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Wang, Kun, Zhu, Chengcheng, He, Yafeng, Zhang, Zhenqin, Zhou, Wen, Muhammad, Nafees, Guo, Yan, Wang, Xiaoyong, and Guo, Zijian
- Subjects
- *
CANCER cells , *PLATINUM , *REACTIVE oxygen species , *BIOENERGETICS , *OVARIAN cancer , *GLYCOLYSIS - Abstract
Cancer cells usually adapt metabolic phenotypes to chemotherapeutics. A defensive strategy against this flexibility is to modulate signaling pathways relevant to cancer bioenergetics. A triphenylphosphonium‐modified terpyridine platinum(II) complex (TTP) was designed to inhibit thioredoxin reductase (TrxR) and multiple metabolisms of cancer cells. TTP exhibited enhanced cytotoxicity against cisplatin‐insensitive human ovarian cancer cells in a caspase‐3‐independent manner and showed preferential inhibition to mitochondrial TrxR. The morphology and function of mitochondria were severely damaged, and the levels of mitochondrial and cellular reactive oxygen species were decreased. As a result, TTP exerted strong inhibition to both mitochondrial and glycolytic bioenergetics, thus inducing cancer cells to enter a hypometabolic state. Blocking both avenues: A triphenylphosphonium‐modified terpyridine platinum(II) complex (see structure) exhibited enhanced cytotoxicity against human ovarian cancer cells and showed strong inhibitory effects on both mitochondrial and glycolytic metabolisms. The morphology and function of mitochondria were severely damaged and the levels of mitochondrial and cellular reactive oxygen species decreased, thus inducing the cells to enter a hypometabolic state. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
37. Polyoxometalates as Potential Next‐Generation Metallodrugs in the Combat Against Cancer.
- Author
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Bijelic, Aleksandar, Aureliano, Manuel, and Rompel, Annette
- Subjects
- *
POLYOXOMETALATES , *ANTINEOPLASTIC agents , *CANCER cells , *CANCER treatment , *CANCER chemotherapy - Abstract
Polyoxometalates (POMs) are an emerging class of inorganic metal oxides, which over the last decades demonstrated promising biological activities by the virtue of their great diversity in structures and properties. They possess high potential for the inhibition of various tumor types; however, their unspecific interactions with biomolecules and toxicity impede their clinical usage. The current focus of the field of biologically active POMs lies on organically functionalized and POM‐based nanocomposite structures as these hybrids show enhanced anticancer activity and significantly reduced toxicity towards normal cells in comparison to unmodified POMs. Although the antitumor activity of POMs is well documented, their mechanisms of action are still not well understood. In this Review, an overview is given of the cytotoxic effects of POMs with a special focus on POM‐based hybrid and nanocomposite structures. Furthermore, we aim to provide proposed mode of actions and to identify molecular targets. POMs are expected to develop into the next generation of anticancer drugs that selectively target cancer cells while sparing healthy cells. Next‐generation metallodrugs: This Review aims to critically evaluate the potential of polyoxometalates, especially organically functionalized hybrid and nanocomposite structures, as future clinically applied metallodrugs in the combat against cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
38. A Dual‐Targeted Organic Photothermal Agent for Enhanced Photothermal Therapy.
- Author
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Wang, Hongyu, Chang, Jinjie, Shi, Mingwan, Pan, Wei, Li, Na, and Tang, Bo
- Subjects
- *
CANCER radiotherapy , *ANTINEOPLASTIC agents , *DRUG development , *CANCER cells , *BIOCOMPATIBILITY - Abstract
The development of highly effective anticancer drugs that cause minimal damage to the surrounding normal tissues is a challenging topic in cancer therapy. Herein, we demonstrate a dual‐targeted organic molecule that functions as a photothermal agent by actively targeting tumor tissue and mitochondria to selectively kill cancer cells. The synthesized photothermal agent exhibited high photothermal conversion efficiency, low cytotoxicity, and good biological compatibility. In vivo experiments showed an excellent tumor inhibitory effect of the dual‐targeted photothermal agent. It takes two targets: A small‐molecule organic photothermal agent with two targeting ligands was designed to actively target tumor tissue and mitochondria and thus selectively kill cancer cells. The resulting antitumor agent (see structure) exhibited a high photothermal conversion efficiency of 37.8 %, low cytotoxicity, and good biocompatibility and showed excellent tumor inhibition in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
39. Gold(III) Complexes for Antitumor Applications: An Overview.
- Author
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Bertrand, Benoît, Williams, Morwen R. M., and Bochmann, Manfred
- Subjects
- *
ANTINEOPLASTIC agents , *BIOINORGANIC chemistry , *DITHIOCARBAMATES , *CANCER cells , *LIGANDS (Chemistry) - Abstract
Abstract: Gold(III) complexes have emerged as a versatile and effective class of metal‐based anticancer agents. The development of various types of ligands capable of stabilizing the AuIII cation and preventing its reduction under physiological conditions, such as chelating nitrogen‐donors, dithiocarbamates and C^N cyclometalled ligands, has opened the way for the exploration of their potential intracellular targets and action mechanisms. At the same time, the bioconjugation of AuIII complexes has emerged as a promising strategy for improving the selectivity of this class of compounds for cancer cells over healthy tissues, and recent developments have shown that combining gold complexes with molecular structures that are specifically recognized by the cell can exploit the cell's own transport mechanisms to improve selective metal uptake. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
40. Cell‐ and Tissue‐Based Proteome Profiling and Dual Imaging of Apoptosis Markers with Probes Derived from Venetoclax and Idasanutlin.
- Author
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Zhu, Dongsheng, Guo, Haijun, Chang, Yu, Ni, Yun, Li, Lin, Zhang, Zhi‐Min, Hao, Piliang, Xu, Yong, Ding, Ke, and Li, Zhengqiu
- Subjects
- *
PROTEOMICS , *APOPTOSIS , *TISSUES , *CANCER cells , *ANTINEOPLASTIC agents , *VENETOCLAX - Abstract
Abstract: Venetoclax (ABT‐199) and idasanutlin (RG7388) are efficient anticancer drugs targeting two essential apoptosis markers, Bcl‐2 and MDM2, respectively. Recent studies have shown that the combination of these two drugs leads to remarkable enhancement of anticancer efficacy, both in vitro and in vivo. In an attempt to disclose the relationships of their protein targets, competitive affinity‐based proteome profiling coupled with bioimaging was employed to characterize their protein targets in the same cancer cell line and tumor tissue. A series of protein hits, including ITPR1, GSR, RER1, PDIA3, Apoa1, and Tnfrsf17 were simultaneously identified by pull‐down/LC–MS/MS with the two sets of affinity‐based probes. Dual imaging was successfully carried out, with the simultaneous detection of Bcl‐2 and MDM2 expression in various cancer cells. This could facilitate the novel diagnostic and therapeutic strategies of dual targeting of Bcl‐2/MDM2. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
41. Identification of Tumor Initiating Cells with a Small‐Molecule Fluorescent Probe by Using Vimentin as a Biomarker.
- Author
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Lee, Yong‐An, Kim, Jong‐Jin, Sahu, Srikanta, Park, Sung‐Jin, Chang, Young‐Tae, Kang, Nam‐Young, Lee, Jungyeol, Wang, Zhenxun, Lim, Bing, Lee, Jia Hui Jane, Tam, Wai Leong, Kwon, Haw‐Young, Jang, Se‐Young, and Lee, Jun‐Seok
- Subjects
- *
FLUORESCENT probes , *CANCER cells , *SMALL molecules , *VIMENTIN , *TUMOR markers , *ANTINEOPLASTIC agents , *HIGH throughput screening (Drug development) - Abstract
Abstract: Tumor initiating cells (TICs) have been implicated in clinical relapse and metastasis of a variety of epithelial cancers, including lung cancer. While efforts toward the development of specific probes for TIC detection and targeting are ongoing, a universal TIC probe has yet to be developed. We report the first TIC‐specific fluorescent chemical probe, TiY, with identification of the molecular target as vimentin, a marker for epithelial‐to‐mesenchymal transition (EMT). TiY selectively stains TICs over differentiated tumor cells or normal cells, and facilitates the visualization and enrichment of functionally active TICs from patient tumors. At high concentration, TiY also shows anti‐TIC activity with low toxicity to non‐TICs. With the unexplored target vimentin, TiY shows potential as a first universal probe for TIC detection in different cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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42. Cytotoxic effect of the serotonergic drug 1-(1-Naphthyl)piperazine against melanoma cells.
- Author
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Menezes, Ana Catarina, Carvalheiro, Manuela, Ferreira de Oliveira, José Miguel P., Ascenso, Andreia, and Oliveira, Helena
- Subjects
- *
MELANOMA , *CANCER cells , *SEROTONINERGIC mechanisms , *CELL-mediated cytotoxicity , *PIPERAZINE - Abstract
1-(1-Naphthyl)piperazine (1-NPZ) is a serotonergic derivative of quipazine acting both as antagonist and agonist of different serotonin receptors, with promising results for the management of skin cancer. In this work, we studied the effect of 1-NPZ on human MNT-1 melanoma cells by evaluating its effects on cell viability, ability to form colonies, cell cycle dynamics, reactive oxygen species (ROS) production and apoptosis. Treatment of MNT-1 cells with 1-NPZ for 24 h decreased cell viability and induced apoptosis in a dose-dependent manner. Activity against melanoma was confirmed with a different melanoma cell line, SK-MEL-28. Simultaneously, 1-NPZ affected cell cycle progression by mediating a S-phase delay. Higher levels of ROS were also detected in MNT-1 cells after treatment with 1-NPZ. Furthermore, 1-NPZ significantly increased the expression of cyclooxygenase-2 in MNT-1 cells. These findings suggest that 1-NPZ pretreatment is able to induce oxidative stress, and consequently apoptotic cell death in melanoma cells. In conclusion, this study demonstrates the cytotoxic and genotoxic potential of 1-NPZ against melanoma cells. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
43. Study on Anti‐Proliferative Activity in Cancer Cells and Preliminary Structure–Activity Relationship of Pseudo‐Peptide Chiral Thioureas.
- Author
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Liao, Peng, Hu, Shi‐Qin, Zhang, Hong, Xu, Liang‐Bi, Liu, Jing‐Zi, He, Bin, Liao, Shang‐Gao, and Li, Yong‐Jun
- Subjects
- *
CANCER cells , *PHOSPHONATES , *ANTINEOPLASTIC agents , *NUCLEAR magnetic resonance , *TUMOR budding - Abstract
In our previous studies, we have shown that thiourea compounds containing phosphate esters have potent antitumor activity and can be used as a novel strategy for the development of antitumor agents. Herein, a series of novel phosphonate thioureas
5–38 have been synthesized, which were fully characterized by 1H NMR, 13C NMR spectrum, elemental analysis. Three human cancer cell lines (Bcap‐37, BGC‐823, and PC‐3) have been used to investigate these compounds’ antitumor activities. After the summarization of the structure–activity relationships, we found that the variation of R, R1, and R2 in these novel phosphonate thioureas contribute to the antitumor activities. All these SAR‐guided efforts may lead to novel antitumor drugs in the market in the near future. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
44. Design, synthesis, and biological evaluation of a new class of benzo[ b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity.
- Author
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Lauria, Antonino, Gentile, Carla, Mingoia, Francesco, Palumbo Piccionello, Antonio, Bartolotta, Roberta, Delisi, Riccardo, Buscemi, Silvestre, and Martorana, Annamaria
- Subjects
- *
BENZOFURAN , *HETEROCYCLIC compound derivatives , *DRUG design , *DRUG synthesis , *CELL lines , *CANCER cells - Abstract
A new series of 3-benzoylamino-5-(1 H-imidazol-4-yl)methylaminobenzo[ b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[ b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure features as antitubulin agents by in silico protocols. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
45. Cytotoxic effect of a family of peroxisome proliferator-activated receptor antagonists in colorectal and pancreatic cancer cell lines.
- Author
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Ammazzalorso, Alessandra, De Lellis, Laura, Florio, Rosalba, Bruno, Isabella, De Filippis, Barbara, Fantacuzzi, Marialuigia, Giampietro, Letizia, Maccallini, Cristina, Perconti, Silvia, Verginelli, Fabio, Cama, Alessandro, and Amoroso, Rosa
- Subjects
- *
ANTINEOPLASTIC antibiotics , *PEROXISOME proliferator-activated receptors , *PANCREATIC cancer , *CANCER cells , *SULFONAMIDES - Abstract
Recent studies report an interesting role of peroxisome proliferator-activated receptor (PPAR) antagonists in different tumor models, being these compounds able to perturb metabolism and viability in cancer cells. In this work, the identification of a novel PPAR antagonist, showing inhibitory activity on PPARα and a weaker antagonism on PPARγ, is described. The activity of this compound and of a series of chemical analogues was investigated in selected tumor cell lines, expressing both PPARα and PPARγ. Data obtained show a dose-dependent cytotoxic effect of the novel PPAR antagonist in colorectal and pancreatic cancer models. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
46. Cancer Stem Cell and Bulk Cancer Cell Active Copper(II) Complexes with Vanillin Schiff Base Derivatives and Naproxen.
- Author
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Lu, Chunxin, Eskandari, Arvin, Cressey, Paul B., and Suntharalingam, Kogularamanan
- Subjects
- *
STEM cells , *CANCER cells , *SCHIFF bases , *METAL complexes , *VANILLIN - Abstract
Four copper(II) complexes, 1- 4 containing regioisomeric vanillin Schiff base derivatives and the nonsteroidal anti-inflammatory drug (NSAID), naproxen, were synthesised and characterised. All complexes effectively cleave DNA in cell-free systems, with 4 displaying the highest nuclease activity. DNA binding studies suggest that 4 binds to DNA via the grooves prior to inducing oxidative DNA cleavage. Three of the complexes ( 1, 3, and 4) indiscriminately kill cancer stem cell (CSC)-enriched cells (HMLER-shEcad) and bulk cancer cells (HMLER) at micromolar concentrations. The most effective complex, 4 also reduced the formation and size of mammospheres to a similar extent as salinomycin, a well-established CSC-potent agent. Mechanistic studies show that 4 is readily taken up by CSCs, elevates intracellular reactive oxygen species (ROS) levels, causes DNA damage, and induces caspase-dependent apoptosis. Furthermore, 4 inhibits cyclooxygenase-2 (COX-2) expression and causes COX-2-dependent CSC death. The advantage of 4 over bulk cancer cell- or CSC-selective agents is that it has the potential to remove whole tumor populations (bulk cancer cells and CSCs) with a single dose. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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- View/download PDF
47. Modular Assembly of Reversible Multivalent Cancer-Cell-Targeting Drug Conjugates.
- Author
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Santos, Fábio M. F., Matos, Ana I., Ventura, Ana E., Gonçalves, João, Veiros, Luís F., Florindo, Helena F., and Gois, Pedro M. P.
- Subjects
- *
CANCER cells , *ANTINEOPLASTIC agents , *TARGETED drug delivery , *BORONIC acids , *COVALENT bonds - Abstract
Herein is described a new modular platform for the construction of cancer-cell-targeting drug conjugates. Tripodal boronate complexes featuring reversible covalent bonds were designed to accommodate a cytotoxic drug (bortezomib), poly(ethylene glycol) (Peg) chains, and folate targeting units. The B-complex core was assembled in one step, proved stable under biocompatible conditions, namely, in human plasma (half-life up to 60 h), and underwent disassembly in the presence of glutathione (GSH). Stimulus-responsive intracellular cargo delivery was confirmed by confocal fluorescence microscopy, and a mechanism for GSH-induced B-complex hydrolysis was proposed on the basis of mass spectrometry and DFT calculations. This platform enabled the modular construction of multivalent conjugates with high selectivity for folate-positive MDA-MB-231 cancer cells and IC50 values in the nanomolar range. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
48. Tumor Targeting with an isoDGR-Drug Conjugate.
- Author
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Zanella, Simone, Angerani, Simona, Pina, Arianna, López Rivas, Paula, Giannini, Clelia, Panzeri, Silvia, Arosio, Daniela, Caruso, Michele, Gasparri, Fabio, Fraietta, Ivan, Albanese, Clara, Marsiglio, Aurelio, Pignataro, Luca, Belvisi, Laura, Piarulli, Umberto, and Gennari, Cesare
- Subjects
- *
CONJUGATE addition reactions , *CONJUGATED polymers , *PACLITAXEL , *CANCER cells , *INTEGRINS - Abstract
Herein we report the first example of an isoDGR-drug conjugate ( 2), designed to release paclitaxel selectively within cancer cells expressing integrin αVβ3. Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin αVβ3 receptor (IC50=11.0 n m). The tumor targeting ability of conjugate 2 was assessed in vitro in anti-proliferative assays on two isogenic cancer cell lines characterized by different integrin αVβ3 expression: human glioblastoma U87 (αVβ3+) and U87 β3-KO (αVβ3−). The isoDGR-PTX conjugate 2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD-PTX conjugate 4 (TI=2.4). [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
49. Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity.
- Author
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Basri, Aida M., Lord, Rianne M., Allison, Simon J., Rodríguez ‐ Bárzano, Andrea, Lucas, Stephanie J., Janeway, Felix D., Shepherd, Helena J., Pask, Christopher M., Phillips, Roger M., and McGowan, Patrick C.
- Subjects
- *
ANTINEOPLASTIC agents , *CANCER cells , *LIGANDS (Chemistry) , *RUTHENIUM compounds , *METAL complexes , *ISOMERS - Abstract
A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
50. Antitumor activity of 3,4-ethylenedioxythiophene derivatives and quantitative structure-activity relationship analysis.
- Author
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Jukić, Marijana, Rastija, Vesna, Opačak-Bernardi, Teuta, Stolić, Ivana, Krstulović, Luka, Bajić, Miroslav, and Glavaš-Obrovac, Ljubica
- Subjects
- *
ANTINEOPLASTIC agents , *THIOPHENE derivatives , *STRUCTURE-activity relationships , *QUANTITATIVE chemical analysis , *CANCER cells - Abstract
The aim of this study was to evaluate nine newly synthesized amidine derivatives of 3,4- ethylenedioxythiophene (3,4-EDOT) for their cytotoxic activity against a panel of human cancer cell lines and to perform a quantitative structure–activity relationship (QSAR) analysis for the antitumor activity of a total of 27 3,4-ethylenedioxythiophene derivatives. Induction of apoptosis was investigated on the selected compounds, along with delivery options for the optimization of activity. The best obtained QSAR models include the following group of descriptors: BCUT, WHIM, 2D autocorrelations, 3D-MoRSE, GETAWAY descriptors, 2D frequency fingerprint and information indices. Obtained QSAR models should be relieved in elucidation of important physicochemical and structural requirements for this biological activity. Highly potent molecules have a symmetrical arrangement of substituents along the x axis, high frequency of distance between N and O atoms at topological distance 9, as well as between C and N atoms at topological distance 10, and more C atoms located at topological distances 6 and 3. Based on the conclusion given in the QSAR analysis, a new compound with possible great activity was proposed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
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