TY - JOUR T1 - Quantitative Structure–Cytotoxicity Relationship of Oleoylamides JF - Anticancer Research JO - Anticancer Res SP - 5341 LP - 5351 VL - 35 IS - 10 AU - HIROSHI SAKAGAMI AU - YOSHIHIRO UESAWA AU - MARIKO ISHIHARA AU - HAJIME KAGAYA AU - TAISEI KANAMOTO AU - SHIGEMI TERAKUBO AU - HIDEKI NAKASHIMA AU - KOICHI TAKAO AU - YOSHIAKI SUGITA Y1 - 2015/10/01 UR - http://ar.iiarjournals.org/content/35/10/5341.abstract N2 - Eighteen oleoylamides were subjected to quantitative structure–activity relationship analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to assess their biological activities. Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and five human oral normal cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell, oral keratinocyte, primary gingival epithelial cells) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-selectivity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal human oral cells to that against OSCC cell lines. Potency-selectivity expression (PSE) was determined by the ratio of TS to CC50 against OSCC. Anti-HIV activity was evaluated by the ratio of CC50 to the concentration leading to 50% cytoprotection from HIV infection (EC50). Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method. Among 18 derivatives, compounds 8 with a catechol group) and 18 with a (2-pyridyl)amino group) had the highest TS. On the other hand, doxorubicin and 5-fluorouracil (5-FU) were more highly cytotoxic to normal epithelial cells, displaying unexpectedly lower TS and PSE values. None of the compounds had anti-HIV activity. Among 330 chemical descriptors, 75, 73 and 19 descriptors significantly correlated to the cytotoxicity to normal and tumor cells, and TS, respectively. Multivariate statistics with chemical descriptors for molecular polarization and hydrophobicity may be useful for the evaluation of cytotoxicity and TS of oleoylamides. ER -