Discovery of 3-(thiophen/thiazole-2-ylthio)pyridine derivatives as multitarget anticancer agents
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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.
KeywordsMultitarget IGF-1R Anti-cancer Kinases
The authors thank the project supported by the key Development Program of the Hangzhou Science and Technology Committee (Grant No. 20152013A03), the Research project on application of public welfare technology supported by Science Technology Department of Zhejiang Province (Grant No. 2017C33233 and LGF18H300001).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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