2. Academic Validation
  3. Design, synthesis and preliminary antiproliferative activity studies of new diheteroaryl thioether derivatives

Design, synthesis and preliminary antiproliferative activity studies of new diheteroaryl thioether derivatives

  • Bioorg Med Chem Lett. 2017 Sep 15;27(18):4377-4382. doi: 10.1016/j.bmcl.2017.08.021.
Zhong-Hua Li 1,  Xue-Qi Liu 1,  Tao-Qian Zhao 1,  Peng-Fei Geng 1,  Ying Liu 1,  Bing Zhao 1,  Wen-Ge Guo 1,  Bin Yu 2,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
  • 2 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: zzuyubin@hotmail.com.
  • 3 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
PMID: 28838695 DOI: 10.1016/j.bmcl.2017.08.021
Abstract

A series of structurally new diheteroaryl thioether analogs was designed, prepared and screened toward MGC-803, MKN-45, EC-109 and H1650. Most of the target compounds displayed moderate to potent antiproliferative activities. Among them, compound 5 showed the best antiproliferative activity against the tested cell lines with the half maximal inhibitory concentration (IC50) values below 10μM. In addition, flow cytometry analysis showed that compound 5 increased Bax expression, down-regulated expression of Bcl-2, cleaved caspases-3/9, finally inducing Apoptosis of MKN-45 cells as well asarrested the cell cycle at G2/M phase. This study suggests that the diheteroaryl thioethers are a class of emerging chemotypes for developing antitumor agents or biological probes, and compound 5 could serve as a good starting point to design new Apoptosis inducers.

Keywords

Antiproliferative activity; Apoptosis; Cell cycle arrest; Diheteroaryl thioether.

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