2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents

A variety of (Z)-[(2H-chromen-3-yl)methylene]azolidinones 6a–t bearing thiazolidine-2,4-dione, rhodanine or hydantoin scaffolds were designed and synthesized as potential anticancer agents. Inhibitory effect of synthesized compounds 6a–t on the viability of cancer and non-cancer cells was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assay. The SAR study revealed that the N-substitution of azolidinone moiety cannot improve the activity but S/NH replacement (thiazolidine-2,4-dione/hydantoin) and S/O alteration (rhodanine/thiazolidine-2,4-dione) enable us to modulate the growth inhibition activity against various cell lines. Moreover, 6-bromo and 2-methyl substituents on chromene ring had positive effects on growth inhibitory activity depending on the tumor cell lines. Among the synthesized compounds, hydantoin derivative 6o with a 6-bromo-2-methyl-2H-chromene substructure showed the best profile of cytotoxicity comparable to that of cisplatin as standard anticancer agent.

Graphical abstractA variety of (Z)-[(2H-chromen-3-yl)methylene]azolidinones bearing thiazolidine-2,4-dione, rhodanine or hydantoin scaffolds were synthesized. Hydantoin derivative 6o with a 6-bromo-2-methyl-2H-chromene substructure showed the best profile of cytotoxicy comparable to that of cisplatin.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of 2H-chromene-derived arylidene-azolidinones were synthesized. ► The cytotoxic activity of compounds was assessed using MTT reduction assay. ► The SAR was explored in thiazolidine-2,4-dione, rhodanine and hydantoin series. ► Hydantoin derivative 6o showed the best profile of cytotoxicy.