Quantitative structure–cytotoxicity relationship of 2-styrylchromones

Abstract

Background/Aim: Studies of biological activity of 2-styrylchromone derivatives focusing on antioxidant, anti-inflammatory, antiviral and antitumor activity are limited. In this study, eighteen synthetic 2-styrylchromone derivatives were investigated for their cytotoxicity against human malignant and non-malignant cells, and then subjected to quantitative structure–activity relationship (QSAR) analysis. Materials and Methods: Tumor-specificity was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against four normal oral cells to that against oral squamous cell carcinoma cell lines. Induction of apoptosis and growth arrest were evaluated by cell-cycle analysis. For QSAR analysis, 3,117 types of physicochemical, structural, and quantum chemical features were calculated from the most stabilized structure of 2-styrylchromone derivatives. Results: Two 2-styrylchromone derivatives in which a methoxy group was introduced at the 4-position of the benzene ring showed tumor-specificity equivalent to or higher than doxorubicin in TS value. These compounds accumulated the subG1 and G2/M phase cells, suggesting the induction of apoptosis. Their tumor-specificity can be explained mainly by molecular shape and electronic state. Conclusion: These findings suggest the applicability of 2-styrylchromone to develop safe and effective anticancer agents as seed compounds.