Abstract

Objective: Benzofurans, fused pyrazole systems, and thiazole moieties are the most important pharmacophores and intermediates for making drugs. The preparation and anti-cancer activity of novel benzofuran-pyrazole-containing amino thiazole hybrids. Methods: The synthesized benzofuran-pyrazole containing amino thiazole hybrids (VIIa–VIIi). The anticancer activity of (VIIa–VIIi) against MCF-7, and A549 cell lines was determined using the MTT-assay, and also screened with in silico molecular docking studies. Results: The most potent compounds (E)-2-(2-((3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(4-chlorophenyl)thiazole (VIIg) and (E)-2-(2-((3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(p-tolyl)thiazole (VIIb) exhibited excellent anticancer activity against the MCF-7 and A549 cancer cell lines. Additionally, the synthesis hybrids and Erlotinib were screened for their in silico molecular docking studies against the EGFR (4HJO) receptor. The compounds (VIIg) and (VIIb) exhibited significantly higher binding scores and inhibitory constants than the reference drug Erlotinib. Conclusions: It has been observed that the substitution on the 4-chloro phenyl ring (VIIg) and 4-methyl phenyl ring (VIIb) important for maintaining their anticancer activity. The outcomes of the kinase inhibitory assay of these significant (VIIg) and (VIIb) hybrids against the tyrosine kinase EGFR strongly corroborated the in vitro anticancer findings and the in silico docking investigations. This research showed that newly developed compounds have potential as anticancer agents and suggested leads for further research.