2. Academic Validation
  3. Design, synthesis and antiproliferative activity of thiazolo[5,4-d]pyrimidine derivatives through the atom replacement strategy

Design, synthesis and antiproliferative activity of thiazolo[5,4-d]pyrimidine derivatives through the atom replacement strategy

  • Eur J Med Chem. 2017 Sep 29:138:1034-1041. doi: 10.1016/j.ejmech.2017.07.039.
Zhong-Hua Li 1,  Xue-Qi Liu 1,  Peng-Fei Geng 1,  Ji Zhang 1,  Jin-Lian Ma 1,  Bo Wang 1,  Tao-Qian Zhao 1,  Bing Zhao 1,  Xin-Hui Zhang 1,  Bin Yu 2,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China.
  • 2 Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China. Electronic address: zzuyubin@hotmail.com.
  • 3 Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China. Electronic address: liuhm@zzu.edu.cn.
PMID: 28759876 DOI: 10.1016/j.ejmech.2017.07.039
Abstract

A series of thiazolo[5,4-d]pyrimidine derivatives were designed through the atom replacement strategy based on biologically validated scaffolds and then evaluated for their antiproliferative activities on Cancer cell lines. The structure-activity relationship studies were conducted, leading to the identification of compound 22, which exhibited good antiproliferative activity against HGC-27 with an IC50 value of 1.22 μM and low toxicity against GES-1 cells. Mechanistic studies showed that compound 22 inhibited the colony formation and migration of HGC-27 as well as induced Apoptosis. The western blot experiments proved that compound 22 up-regulated expression of Bax, down-regulated expression levels of Bcl-2 and cleaved caspased-3/9. These findings indicate that compound 22 may serve as a template for designing new agents for the treatment of human gastric cancers. The atom replacement strategy could be viable strategy for designing new Anticancer drugs and may find its applications in drug design.

Keywords

Antiproliferative activity; Apoptosis; Atom replacement; Thiazolo[5,4-d]pyrimidine.

Figures