1. Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers
- Author
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Fu, Dong-Jun, Song, Jian, Hou, Yu-Hui, Zhao, Ruo-Han, Li, Jia-Huan, Mao, Ruo-Wang, Yang, Jia-Jia, Li, Ping, Zi, Xiao-Lin, Li, Zhong-Hua, Zhang, Qing-Qing, Wang, Fei-Yan, Zhang, Sai-Yang, Zhang, Yan-Bing, and Liu, Hong-Min
- Subjects
Medicinal and Biomolecular Chemistry ,Organic Chemistry ,Chemical Sciences ,Cancer ,Antineoplastic Agents ,Apoptosis ,Cell Cycle ,Cell Line ,Tumor ,Cell Proliferation ,Dose-Response Relationship ,Drug ,Drug Discovery ,Drug Screening Assays ,Antitumor ,Humans ,Molecular Structure ,Structure-Activity Relationship ,Triazines ,5 ,6-Diaryl-1 ,2 ,4-triazines ,Molecular hybridization strategy ,Morphological changes ,Apoptosis-related proteins ,Pharmacology and Pharmaceutical Sciences ,Medicinal & Biomolecular Chemistry ,Pharmacology and pharmaceutical sciences ,Medicinal and biomolecular chemistry ,Organic chemistry - Abstract
A series of 5,6-diaryl-1,2,4-triazines hybrids bearing a 1,2,3-triazole linker were synthesized by molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, EC-109 and PC-3). The first structure-activity relationship (SAR) for these 5,6-diaryl-1,2,4-triazines is explored in this report with evaluation of 15 variants of the structural class. Among these chemical derivatives, 3-(((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-diphenyl-1,2,4-triazine (11E) showed the more potent inhibitory effect against three cell lines than 5-Fu. Cellular mechanism studies in MGC-803 cells elucidated 11E inhibited colony formation and arrested cell cycle at G2/M phase. Furthermore, compound 11E caused morphological changes, decreased mitochondrial membrane potential, and induced apoptosis through the apoptosis-related proteins in MGC-803 cells. It was the first time, to our knowledge, that 5,6-diaryl-1,2,4-triazines bearing a 1,2,3-triazole linker were used as potential apoptosis inducers.
- Published
- 2017