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Eur J Med Chem. 2017 Jul 28;135:204-212. doi: 10.1016/j.ejmech.2017.04.056. Epub 2017 Apr 22.

Identification of thiazolo[5,4-d]pyrimidine derivatives as potent antiproliferative agents through the drug repurposing strategy.

Author information

1
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of 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, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of 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, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of 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.

Abstract

A series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated for their antiproliferative activities on three cancer cell lines. The structure-activity relationship studies were conducted through the variation in the three regions of the thiazolo-pyrimidine core. Substitution with morpholine led to compound 24, which exerted the most potent antiproliferative activity as well as good selectivity between cancer and normal cells (IC50 values of 1.03 μM against MGC803 and 38.95 μM against GES-1). In addition, compound 24 inhibited the colony formation and migration of MGC803 as well as induced apoptosis. Western blot experiments indicated the expression changes of apoptosis-related proteins, including up-regulation of Bax and caspase-3/9, as well as down-regulation of Bcl-2.

KEYWORDS:

Antiproliferative activity; Apoptosis; Drug repurposing; Thiazolo[5,4-d]pyrimidine

PMID:
28456031
DOI:
10.1016/j.ejmech.2017.04.056
[Indexed for MEDLINE]

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