Abstract
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•New hydrazonoyl sulfonylthiazoles were designed and synthesized as EGFR inhibitors affecting both MCF-7 and HepG2 cancer cell lines.•Compounds 3, 4, 8a,b, 10a, 14b displayed significant anticancer activities more potent inhibitory effect than dasatinib.•The safety profile of the most active compounds (3, 4, 8a, b, 10a, 14b) was assessed against the normal WI-38 cell line.•Docking study results revealed great affinities inside the binding site of EGFR.
New hydrazonoyl-sulfonylthiazoles were designed and synthesized as EGFR inhibitors. The new sulfonylthiazole derivatives were assessed in vitro to measure their effect on EGFR. They revealed marked inhibitory activity against EGFR kinase having IC50 range from 0.037 to 0.317 μM compared to reference drug dasatinib (IC50 = 0.077 μM). Six derivatives of the newly synthesized compounds showed potent inhibitory activity relative to dasatinib. Furthermore, the new hits were examined concerning their cytotoxic effect on human breast cancer cell line (MCF7), hepatic cancer cell line (HepG2) using MTT assay. N-(2-Benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-thiazol-2-yl)-hydrazine (IC50 = 1.24 μM) revealed higher potency than dasatinib (IC50 = 11.6 μM) against MCF7cell line. Besides, N-(2-benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-5-p-tolylazo-thiazol-2-yl)-hydrazine exhibited excellent cytotoxicity against HepG2cell line (IC50 = 3.61 μM), exceeding that of dasatinib (IC50 = 14.10 μM). In addition to low cytotoxic effect on normal (WI-38) cells, describing the high safety profiles of these compounds. Moreover, molecular docking was done in order to determine the possible binding modes of such compounds inside the binding site of EGFR.