1. Discovery of 3-(thiophen/thiazole-2-ylthio)pyridine derivatives as multitarget anticancer agents
- Author
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Huajian Zhu, Jiankang Zhang, Linghui Zeng, Jingyi Lu, Liping Fu, Rangxiao Zhuang, Jianjun Xi, Limin Kong, Yanmei Zhao, Shourong Liu, Ruoyu He, Chong Zhang, Rujia Tao, and Zhengmengtong Liu
- Subjects
Cell cycle checkpoint ,010405 organic chemistry ,Chemistry ,Kinase ,Stereochemistry ,Organic Chemistry ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Cell culture ,Pyridine ,General Pharmacology, Toxicology and Pharmaceutics ,Thiazole ,Tyrosine kinase ,IC50 ,K562 cells - Abstract
A series of novel 3-(thiophen/thiazole-2-ylthio)pyridine derivatives were designed and synthesized as IGF-1R tyrosine kinase inhibitors. All the target compounds were tested for their IGF-1R kinase inhibitory activities and cytotoxicities against five cancer cell lines (K562, Hep-G2, HCT-116, WSU-DLCL2, and A549). Although all these compounds exhibited moderate to potent cancer cell proliferation inhibitory activities (the most potent compound 43 showed IC50 value of 1.3 ± 0.9 μM against WSU-DLCL2 cell line), IGF-1R inhibition were not observed. In order to identify the exact target of these analogues, selected compounds were further screened for various kinases. The results indicated that this series of compounds may exert their anticancer activities through inhibiting various kinases including FGFR 3, EGFR, JAK, and RON. In addition, cell cycle analysis of compound 43 on Hep-G2 cells showed cell cycle arrest at G1/G0 phase. All the experiments validated the potential of 3-(thiophen/thiazole-2-ylthio)pyridine analogues as multi-target anticancer agents.
- Published
- 2019
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