Design, Synthesis, Antimicrobial and Antitumor Activities of Benzo[f]chromene Derivatives: DFT and Molecular Docking.

Abstract

Introduction: Benzochromenes are heterocyclic compounds of growing interest in medicinal chemistry due to their diverse biological activities, including antioxidant, anticancer, and antimicrobial properties.

Methods: A one-pot, three-component synthesis was employed to prepare benzochromene derivatives (4a-f) using 2-naphthol or its derivatives, active methylene compounds, and 2-methoxybenzaldehyde in ethanol with piperidine as a catalyst. The compounds were evaluated for their anticancer activity against MCF-7, HepG-2, and HCT-116 cell lines, as well as for their antimicrobial activity through molecular docking studies targeting cancerrelated and microbial proteins.

Results: All synthesized compounds were obtained in moderate to good yields. Compounds 4c, 4e, and 4f demonstrated superior biological activity compared to standard drugs Doxorubicin and Augmentin. Docking studies revealed strong binding affinities to key targets, including the TGF-βI receptor and the choline-binding domain.

Discussion: The hydroxyl group at position 9 in compounds 4c and 4f likely contributed to enhanced antimicrobial activity, while the bromo group in 4e correlated with significant anticancer effects. These findings suggest meaningful structure-activity relationships and validate the design strategy.

Conclusion: The synthesized benzochromene derivatives exhibit promising anticancer and antimicrobial activities. Supported by molecular docking, these findings lay the groundwork for further pharmacological and in vivo evaluations of this scaffold.