RT Journal Article SR Electronic T1 Quantitative Structure–Cytotoxicity Relationship of Newly Synthesized Piperic Acid Esters JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6161 OP 6168 VO 37 IS 11 A1 HIROSHI SAKAGAMI A1 YOSHIHIRO UESAWA A1 YOSHIKO MASUDA A1 MINEKO TOMOMURA A1 SATOSHI YOKOSE A1 TAKAKI MIYASHIRO A1 JUNICHI MURAI A1 KOICHI TAKAO A1 TAISEI KANAMOTO A1 SHIGEMI TERAKUBO A1 HAJIME KAGAYA A1 HIDEKI NAKASHIMA A1 YOSHIAKI SUGITA YR 2017 UL http://ar.iiarjournals.org/content/37/11/6161.abstract AB Background/Aim: Eleven piperic acid 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 cells to that against tumor 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: One phenylmethyl ester and five phenylethyl esters showed relatively higher cytotoxicity and tumor specificity, that were significantly modified by introduction of hydroxyl and methoxy groups. On the other hand, phenylpropyl ester, phenylbutyl ester and decyl ester were essentially inactive. (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid 2-(3,4-dihydroxyphenyl)ethyl ester [4] had the highest TS and PSE values. This compound also stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. TS values were correlated with molecular size, ionization potential, molecular shape, ionization potential and electronegativity. None of the compounds had any anti-HIV activity. Conclusion: Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs.