TY - JOUR T1 - Quantitative Structure–Activity Relationship Analysis of Cytotoxicity and Anti-UV Activity of 2-Aminotropones JF - Anticancer Research JO - Anticancer Res SP - 1743 LP - 1750 VL - 34 IS - 4 AU - SHOTA SEKINE AU - CHISATO SHIMODAIRA AU - YOSHIHIRO UESAWA AU - HAJIME KAGAYA AU - YUMIKO KANDA AU - MARIKO ISHIHARA AU - OSAMU AMANO AU - HIROSHI SAKAGAMI AU - HIDETSUGU WAKABAYASHI Y1 - 2014/04/01 UR - http://ar.iiarjournals.org/content/34/4/1743.abstract N2 - Background: We newly synthesized twenty 2-aminotropones with different lengths of methylene units, with or without introduction of isopropyl group at C-4 position of the cycloheptatriene ring, which were then subjected to quantitative structure–activity relationship (QSAR) analysis. Materials and Methods: Viable cell number was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The tumor specificity was determined by the ratio of the mean CC50 (50% cytotoxic concentration) for the normal cells (human gingival fibroblast, HGF) to that of the human oral squamous cell carcinoma (OSCC) cell line (Ca9-22) derived from gingival tissue. Anti-UV activity (SI) was determined by the ratio of CC50 to EC50 (the concentration that increased the viability of UV-irradiated cells to 50%) using HSC-2 OSCC cells. Physico-chemical, structural, and quantum-chemical parameters were calculated based on conformations optimized by the LowModeMD method followed by the Discrete Fourier Transform (DFT) method. Fine-cell structure was observed by transmission electron microscopy. Results: 2-Aminotropones induced cytotoxicity, accompanied by the production of many rough endoplasmic reticula with enlarged lacuna and vacuolated mitochondria. Their cytotoxicity was a positive function of the number of methylene units and hydrophobicity. Anti-UV activity showed a good correlation with lowest unoccupied molecular orbital (LUMO) energy, but not with the length of methylene units. All twenty 2-aminotropones induced a very low level of hormetic growth stimulation at lower concentrations. Conclusion: Different types of chemical descriptors may be applicable to estimating the cytotoxicity and anti-UV activity of 2-aminotropones. ER -