TY - JOUR T1 - Quantitative Structure–Cytotoxicity Relationship of Cinnamic Acid Phenetyl Esters JF - Anticancer Research JO - Anticancer Res SP - 817 LP - 823 VL - 38 IS - 2 AU - YOSHIHIRO UESAWA AU - HIROSHI SAKAGAMI AU - NORIYUKI OKUDAIRA AU - KAZUHIRO TODA AU - KOICHI TAKAO AU - HAJIME KAGAYA AU - YOSHIAKI SUGITA Y1 - 2018/02/01 UR - http://ar.iiarjournals.org/content/38/2/817.abstract N2 - Background/Aim: Many phenolic acid phenethyl esters possess diverse biological effects including antioxidant, cytoprotective, anti-inflammation and anti-tumor activities. However, most previous antitumor studies have not considered the cytotoxicity against normal cells. Ten cinnamic acid phenetyl esters were subjected to quantitative structure–activity relationship (QSAR) analysis, based on their cytotoxicity and tumor-specificity, in order to find their new biological activities. Materials and Methods: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal 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 oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value 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. Results: Western blot analysis demonstrated that [9] stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. QSAR analysis demonstrated that TS values were correlated with shape, size and ionization potential. Conclusion: Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs. ER -