Design, synthesis and pharmacological evaluation of novel thiazole derivatives as c-Met kinase inhibitors and anticancer agents

Abstract

In search of novel anticancer agents, the design and synthesis of novel sixteen thiazole derivatives (7a-p) have been reported along with their characterization using 1H NMR, 13C NMR, FT-IR, MS, and HPLC. All the synthesized compounds were evaluated against c-Met kinase, followed by anticancer evaluation of the most promising compounds using the MTT assay. The results of these studies identified compound 7a with an IC50 value of 0.4 nM against c-Met kinase along with good anticancer activity against HT29 (IC50 = 7.79 µM, SI of 6.33) and MDA-MB-231 (IC50 = 5.78 µM, SI of 8.65) cancer cell lines. In order to study the in-depth binding interactions of all the synthesized compounds at the active site of c-Met kinase using molecular docking, the typical U-shaped bent conformation of the identified compounds was predicted for all synthesized compounds. Compounds 7a and 7j were found with the best binding energy of −7.98 and −8.26 kcal/mol, respectively. The present work has led to the start-point in the design and discovery of thiazole derivatives as novel c-Met kinase inhibitors and potential anticancer agents.