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

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

  • Eur J Med Chem. 2017 Sep 29:138:1076-1088. doi: 10.1016/j.ejmech.2017.07.011.
Dong-Jun Fu 1,  Jian Song 1,  Yu-Hui Hou 1,  Ruo-Han Zhao 1,  Jia-Huan Li 1,  Ruo-Wang Mao 1,  Jia-Jia Yang 1,  Ping Li 1,  Xiao-Lin Zi 2,  Zhong-Hua Li 1,  Qing-Qing Zhang 1,  Fei-Yan Wang 1,  Sai-Yang Zhang 3,  Yan-Bing Zhang 4,  Hong-Min Liu 5
Affiliations

Affiliations

  • 1 New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, China; Key Laboratory of Technology of Drug Preparation, Zhengzhou University, Ministry of Education, China; Key Laboratory of Henan Province for Drug Quality and Evaluation, China.
  • 2 Pathology and Laboratory Medicine, University of California, Irvine, Orange, CA 92868, USA.
  • 3 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: celeron16@163.com.
  • 4 New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, China; Key Laboratory of Technology of Drug Preparation, Zhengzhou University, Ministry of Education, China; Key Laboratory of Henan Province for Drug Quality and Evaluation, China. Electronic address: zhangyb@zzu.edu.cn.
  • 5 New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, China; Key Laboratory of Technology of Drug Preparation, Zhengzhou University, Ministry of Education, China; Key Laboratory of Henan Province for Drug Quality and Evaluation, China. Electronic address: liuhm@zzu.edu.cn.
PMID: 28763643 DOI: 10.1016/j.ejmech.2017.07.011
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.

Keywords

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

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