Synthesis of chromene derivatives from dimedone and their anti-proliferative studies

The aim of this study was to design and synthesize a series of novel coumarin derivatives bearing various substituents and heterocyclic rings, and to evaluate their anti-proliferative activity against a panel of six cancer cell lines: A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. The results showed that the most cytotoxic compounds were the twenty-one compounds 4c, 4f, 6a, 6c, 6f, 6g, 6h, 6i, 8a, 8b, 8c, 8f, 8g, 8h, 8i, 9a, 9c, 9f, 9g, 9h, and 9i where such compounds showed inhibitions < 1.0 µM. The target compounds were prepared through the condensation of dimedone, aromatic aldehydes, and acetylnaphthalene derivatives, affording xanthene- and acridine-based structures. Compounds obtained in this work were synthesized through multi-component reactions and were obtained in high yields. The anti-cancer potential of the synthesized compounds was assessed against six different cancer cell lines, including hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa). A structure–activity relationship (SAR) analysis was also performed to correlate structural features with biological activity. Notably, the fused pyran and pyridine derivatives obtained in this study exhibited potent cytotoxicity against the tested cancer cell lines. KEY WORDS: Dimedone, Multicomponent, Choumarin, Arylhydrazo derivatives, Cytotoxicity Bull. Chem. Soc. Ethiop. 2026, 40(4), 823-841. DOI: https://dx.doi.org/10.4314/bcse.v40i4.8