Synthesis and antiproliferative activity studies of new functionalized pyridine linked thiazole derivatives

Ten new pyridine linked various substituted thiazole hybrids through (hydrazonomethyl) phenoxy-acetamide spacer were synthesized. The synthetic strategy was based on the reaction of the precursor 2-(4-((2-carbamothioylhydrazono)methyl)phenoxy)-N-(pyridin-2-yl)acetamide (3) with various alpha-halogenated carbonyl compounds (namely; phenacyl bromides, ethyl bromoacetate, diethyl bromomalonate and 3-chloropentane-2,4-dione). Moreover, the cytotoxicity properties of the synthesized compounds have been studied against liver carcinoma (HepG2), laryngeal carcinoma (Hep-2), prostate cancer (PC3), breast cancer (MCF-7) and normal fibroblast cells (W138). The pyridine-thiazole compounds 7 and 10 revealed promising anticancer activity against MCF-7 and HepG2 cell lines with IC50 values in the range 5.36-8.76 mu M compared to the activity of 5-fluorouracil. Docking study provided valuable insights for binding sites of the synthesized compounds with Rho-associated protein kinase (ROCK-1). (C) 2020 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

Ten new pyridine-linked thiazole hybrids were synthesized using a specific strategy, and their cytotoxicity against various cancer cell lines was studied. Two of the compounds showed promising anticancer activity.