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

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-1 H -pyrazol-1-yl)thiazol-4(5 H )-one ( E28 ) displayed the most potent inhibitory activity (IC 50  = 0.24 μM for EGFR and IC 50  = 1.07 μM 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 0.70 μM, 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.