論文 - 詳細
| RRC ID | 54111 |
|---|---|
| 著者 | Uesawa Y, Sakagami H, Shi H, Hirose M, Takao K, Sugita Y. |
| タイトル | Quantitative Structure-Cytotoxicity Relationship of Furo[2,3-b]chromones. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:The furo[2,3-b]chromone derivatives are natural products that have been used as folklore medicines for various diseases. Here, the cytotoxicity of 12 synthesized furo[2,3-b]chromone derivatives was investigated and subjected to quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS:Cytotoxicity against three human oral squamous cell carcinoma cell lines and three types of 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 as the ratio of the mean 50% cytotoxic concentration (CC50) against normal oral cells to that against carcinoma cell lines. Potency-selectivity expression (PSE) was calculated by dividing the TS value by CC50 against tumor cells. Apoptosis induction was evaluated by cell morphology and caspase-3 activation. Morphological changes were monitored under light microscopy. For QSAR analysis, 288 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using Corina. RESULTS:Four furo[2,3-b]chromone derivatives showed relatively strong tumor selectivity. In particular, the derivatives with phenylethenyl and methoxy groups showed the highest TS, equivalent to that of melphalan, although their PSE values did not reach those of doxorubicin and 5-fluorouracil. Microscopical observation demonstrated that at cytotoxic concentrations, (2R,3aR,9aR)-rac-3a,9a-dihydro-7-methoxy-4-oxo-2-(2-phenylethenyl)-4H-furo[2,3-b][1]benzopyran-3,3(2H)-dicarboxylic acid 3,3-dimethyl ester and (2R,3aR,9aR)-rac-3a,9a-dihydro-7-methoxy-4-oxo-2-(1-propen-1-yl)-4H-furo[2,3-b][1]benzopyran-3,3(2H)-dicarboxylic acid 3,3-dimethyl ester did not produce a population of shrunken cells typical of apoptotic cells, in contrast to cells treated with actinomycin D. Tumor selectivity of furo[2,3-b]chromone derivatives strongly correlated with features related to the number of intramolecular unsaturated bonds, molecular flexibility, molecular density, lipophilicity, molecular size, and molecular shape. CONCLUSION:Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drug. |
| 巻・号 | 38(6) |
| ページ | 3283-3290 |
| 公開日 | 2018-6-1 |
| DOI | 10.21873/anticanres.12593 |
| PII | 38/6/3283 |
| PMID | 29848675 |
| MeSH | Apoptosis / drug effects* Cell Line, Tumor Cell Survival / drug effects Cells, Cultured Chromones / chemistry* Chromones / pharmacology* Dose-Response Relationship, Drug Fibroblasts / drug effects Humans Molecular Structure Mouth / cytology Mouth Neoplasms / pathology Quantitative Structure-Activity Relationship* |
| IF | 1.994 |
| 引用数 | 2 |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) HSC-2(RCB1945) HSC-4(RCB1902) |