Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors

Bioorganic & Medicinal Chemistry
Ke-Ming QiuHai-Liang Zhu

Abstract

A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC(50)=0.24μM for EGFR and IC(50)=1.07μM for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC(50) value of 0.30, 0.54, and 0.70μM, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent.

Citations

Aug 17, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hai-Chao WangHai-Liang Zhu
Aug 19, 2014·Journal of Computer-aided Molecular Design·Juan Felipe Franco-GonzalezJavier Martinez-Salazar
Apr 12, 2016·Archiv der Pharmazie·Aliya M S El NewahieKhaled A M Abouzid
Dec 5, 2018·European Journal of Medicinal Chemistry·M MontanaP Vanelle

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