Quantitative Structure-Cytotoxicity Relationship of Aurones.

Abstract

Seventeen aurones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor-specificity, in order to find their new biological activities. Cytotoxicity against three human oral squamous cell carcinoma cell lines and three oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal cells to that against tumor cell lines. Potency-selectivity expression (PSE) value was calculated by dividing TS by CC50 against tumor cells. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization. Sixteen out of seventeen aurones showed relatively higher cytotoxicity and tumor specificity. Among them, (2Z)-2-[(4-hydroxyphenyl)methylene]-3(2H)-benzofuranone [7] showed the highest TS value and PSE values, comparable with those of doxorubicin and higher than 5-FU, respectively. TS values were correlated with molecular shape, size and polarizability rather than the types of substituted groups. Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs.