2. Academic Validation
  3. Discovery of [1,2,4]triazolo[1,5-a]pyrimidines derivatives as potential anticancer agents

Discovery of [1,2,4]triazolo[1,5-a]pyrimidines derivatives as potential anticancer agents

  • Eur J Med Chem. 2021 Feb 5:211:113108. doi: 10.1016/j.ejmech.2020.113108.
Jin-Ling Huo 1,  Shuai Wang 2,  Xiao-Han Yuan 1,  Bin Yu 3,  Wen Zhao 4,  Hong-Min Liu 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences and Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China.
  • 2 School of Pharmaceutical Sciences and Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China; Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
  • 3 School of Pharmaceutical Sciences and Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: zzuyubin@hotmail.com.
  • 4 School of Pharmaceutical Sciences and Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: zhaowen@zzu.edu.cn.
  • 5 School of Pharmaceutical Sciences and Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: liuhm@zzu.edu.cn.
PMID: 33385852 DOI: 10.1016/j.ejmech.2020.113108
Abstract

In this work, we reported the discovery of compound 6i with potent antiproliferative activity against MGC-803. Among these compounds, the most potent compound 6i could effectively inhibit MGC-803 (IC50 = 0.96 μM), being around 38-fold selectivity over GES-1. Further underlying mechanism studies indicated that 6i inhibited the colony formation, migration of MGC-803, and exerted anti-proliferative effect by inducing G0/G1 phase arrest in MGC-803 cells. Cell Apoptosis was induced by 6i through activating mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway. 6i induced cell Apoptosis by elevating the level of ROS. Also, 6i up-regulated pro-apoptotic Bax and p53 level, while down-regulating anti-apoptotic Bcl-2 protein expression. Furthermore, acute toxicity experiment indicated 6i exhibited good safety in vivo. Therefore, 6i may be a template for future development of [1,2,4]triazolo [1,5-a]pyrimidine-based anti-cancer agents.

Keywords

Anticancer agents; Antiproliferative activity; [1,2,4]triazolo[1,5-a]pyrimidines.

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