Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers

作者：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; Liu, Hong-Min

来源：European Journal of Medicinal Chemistry, 2017, 138: 1076-1088.

DOI：10.1016/j.ejmech.2017.07.011

• 5,6-Diaryl-1,2,4-triazines
• Molecular hybridization strategy
• Morphological changes
• Apoptosis
• Apoptosis-related proteins

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-fluorobenzy1)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-dipheny1-1,2,4-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.

• 出版日期2017-9-29
• 单位郑州大学