Background: The mechanism of cytotoxicity induction by flavonoids has been studied by many investigators, but their tumor specificity is not clear. To address this point, 10 licorice flavonoids were subjected to quantitative structure-activity relationship (QASR) analysis with cytotoxicity assay with four human oral carcinoma and three normal cell lines.
Materials and methods: Cytotoxicity was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. Physico-chemical, structural, and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method.
Results: Licurazid and isoliquiritigenin had the highest cytotoxicity against tumor cells, and liquiritin, isoliquiritin and licurazid had the highest tumor specificity, suggesting an antitumor potential for licurazid. Chalcones had slightly higher cytotoxicity and tumor specificity than flavanones. The number of sugar units in the molecule was somewhat negatively-correlated with cytotoxicity, but not with tumor specificity. Parameters that reflect the three-dimensional structure, molecular volume and number of phenolic OH groups were significantly correlated with cytotoxicity, but not with tumor specificity. On the other hand, solvation energy was significantly correlated with tumor specificity, but not with cytotoxicity.
Conclusion: These physicochemical descriptors may be useful to estimate cytotoxicity or tumor specificity of structurally-related compounds to these licorice flavonoids.
Keywords: Licorice flavonoids; QSAR; chemical descriptor; cytotoxicity; tumor-specificity index.