TY - JOUR T1 - Quantitative Structure–Cytotoxicity Relationship of 2-Azolylchromones JF - Anticancer Research JO - Anticancer Res SP - 763 LP - 770 VL - 38 IS - 2 AU - HIROSHI SAKAGAMI AU - NORIYUKI OKUDAIRA AU - YOSHIHIRO UESAWA AU - KOICHI TAKAO AU - HAJIME KAGAYA AU - YOSHIAKI SUGITA Y1 - 2018/02/01 UR - http://ar.iiarjournals.org/content/38/2/763.abstract N2 - Background/Aim: Twenty-four 2-azolylchromones 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 two human oral squamous cell carcinoma cell lines and two human normal oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against oral cells to that against 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: Three sets of 4H-1-benzopyran-4-ones with indole ring showed much higher TS values than those with pyrrole, pyrazole, imidazole, 1,2,4-triazole, 1,2,3-triazole, indazole and benzimidazole rings. Among those with an indole ring, the compound having a 6-methoxy group, that exhibited the highest cytotoxicity, yielded one to three-order higher PSE values to compared with other groups of compounds. Western blot analysis demonstrated that this compound stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. QSAR analysis demonstrated that TS values were correlated with 3D shape, polarizability, ionization potential and lipophilicity. Conclusion: Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drug. ER -