introduction: Aim: The study aims to design, synthesize, and characterize novel coumarin analogues and evaluate their anticancer activity against MCF-7 (breast cancer) and HEP-G2 (liver cancer) cell lines. Objective: The primary objective is to investigate the biological effects of synthesized coumarin derivatives, focusing on their potential as inhibitors of the epidermal growth factor receptor (EGFR), which is implicated in various cancers. materials and methods: Coumarin derivatives 5a – 5k were synthesized through a three-step process involving reaction with nitro benzyl bromide, reduction, and acylation. Molecular docking was used to assess their binding affinity with the EGFR kinase receptor, comparing results to the standard drug erlotinib. Cytotoxicity was evaluated via the Sulforhodamine B (SRB) assay at concentrations of 10, 20, 40, and 80 µg/ml to determine GI₅₀ values. results: Eleven coumarin derivatives were successfully synthesized. Compound 5d (3-chloro, 4-fluoro substituents) exhibited the strongest EGFR binding affinity (-9.4 kcal/mol), outperforming erlotinib (-6.5 kcal/mol). Against MCF-7 cells, compounds 5b, 5c, 5d, 5e, and 5g showed potent activity with GI₅₀ values below 10 µM. For HEP-G2 cells, only compound 5g demonstrated moderate efficacy (GI₅₀ =14.4 µM). discussion: The structure-activity relationship highlighted that halogen substituents significantly enhanced anticancer activity. conclusion: The synthesized novel coumarin derivatives with promising anticancer properties, particularly against breast cancer cells. Compound 5d stands out as a potential lead for further development due to its strong binding affinity to EGFR and significant cytotoxic effects on MCF-7 cells. These findings support further exploration of coumarin analogues as effective chemotherapeutic agents.
Kumbhar et al. (Wed,) studied this question.