論文 - 詳細
| RRC ID | 52581 |
|---|---|
| 著者 | Sakagami H, Okudaira N, Uesawa Y, Takao K, Kagaya H, Sugita Y. |
| タイトル | Quantitative Structure-Cytotoxicity Relationship of 2-Azolylchromones. |
| ジャーナル | Anticancer Res |
| Abstract |
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. |
| 巻・号 | 38(2) |
| ページ | 763-770 |
| 公開日 | 2018-2-1 |
| DOI | 10.21873/anticanres.12282 |
| PII | 38/2/763 |
| PMID | 29374700 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / pathology Chromones / chemistry* Chromones / pharmacology* Humans Mouth Neoplasms / drug therapy Mouth Neoplasms / pathology Quantitative Structure-Activity Relationship* Tumor Cells, Cultured |
| IF | 1.994 |
| 引用数 | 6 |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) HSC-2(RCB1945) |