Quantitative Structure-Cytotoxicity Relationship of Chalcones.

Abstract

Fifteen chalcones 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 four 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. Apoptosis markers were detected by western blot analysis. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization. Among 15 chalcone derivatives, (2E)-1-(2,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one had the highest TS and PSE values, comparable with those of doxorubicin and methotrexate, respectively. This compound also stimulated the cleavage of poly(ADP-ribose) polymerase and caspase-3. Chalone TS values were correlated with molecular shape and polarization rather than the types of substituted groups. None of the compounds had any anti-HIV activity. Chemical modification of the lead compound may be a potential choice for designing new types of anticancer drugs.