論文 - 詳細
| RRC ID | 44997 |
|---|---|
| 著者 | Sekine S, Shimodaira C, Uesawa Y, Kagaya H, Kanda Y, Ishihara M, Amano O, Sakagami H, Wakabayashi H. |
| タイトル | Quantitative structure-activity relationship analysis of cytotoxicity and anti-UV activity of 2-aminotropones. |
| ジャーナル | Anticancer Res |
| Abstract |
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. |
| 巻・号 | 34(4) |
| ページ | 1743-50 |
| 公開日 | 2014-4-1 |
| PII | 34/4/1743 |
| PMID | 24692705 |
| MeSH | Cell Line Cell Survival / drug effects Cells, Cultured Child Dose-Response Relationship, Drug Female Fibroblasts / drug effects Fibroblasts / radiation effects Humans Molecular Structure Quantitative Structure-Activity Relationship* Tropolone / analogs & derivatives* Tropolone / chemistry Tropolone / pharmacology Tropolone / toxicity |
| IF | 1.994 |
| 引用数 | 3 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) |