Design and Synthesis of Novel Biginelli Adducts: Anticancer Activity and In Silico Study

Abstract

ABSTRACT In this study, we report the synthesis of 14 Biginelli adducts and the evaluation of their anticancer activity against three human cancer cell lines: MCF‐7 (breast), SW480 (colon), and Hep‐G2 (liver), as well as the noncancerous Hek‐293 cell line. Among the synthesized derivatives, compound 8n emerged as the most potent, inducing significant cytotoxicity and apoptosis in MCF‐7 cells. Structure–activity relationship (SAR) analysis showed that specific modifications, such as methyl and nitro substitutions, enhanced anticancer activity, whereas bulky substituents reduced potency. Further investigations confirmed that compound 8n induces cell cycle arrest at the S and G2/M phases, highlighting its antiproliferative mechanism. Molecular docking and molecular dynamics simulations suggest that compound 8n could bind to Eg5, a potential regulator of cell division. However, this study did not include direct biochemical testing of the protein target (Eg5).