論文 - 詳細
| RRC ID | 45326 |
|---|---|
| 著者 | Shimada C, Uesawa Y, Ishii-Nozawa R, Ishihara M, Kagaya H, Kanamoto T, Terakubo S, Nakashima H, Takao K, Sugita Y, Sakagami H. |
| タイトル | Quantitative structure-cytotoxicity relationship of 3-styrylchromones. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND:Fifteen 3-styrylchromones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to explore their biological activities. MATERIALS AND METHODS:Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-selectivity was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal human oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method followed by the density functional theory (DFT) method. RESULTS:All 3-styrylchromone derivatives showed moderate-to-high tumor selectivity. Especially, compounds that have a methoxy group at 6-position of the chromone ring and hydroxyl group at 4'-position of phenyl group in styryl moiety [ 11: ] showed the highest tumor-selectivity. On the other hand, their cytotoxicity against normal cells showed good correlation to the descriptors that reflect hydrophobic interaction and molecular shapes. CONCLUSION:Multivariate statistics with chemical descriptors for the location of substituted group, molecular shape and electrostatic interaction may be useful for designing the most favorable compound with higher tumor selectivity. |
| 巻・号 | 34(10) |
| ページ | 5405-11 |
| 公開日 | 2014-10-1 |
| PII | 34/10/5405 |
| PMID | 25275035 |
| MeSH | Anti-HIV Agents / chemistry Anti-HIV Agents / pharmacology Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology Cell Line Cell Line, Tumor Chromones / chemistry* Chromones / toxicity* Humans Molecular Structure Quantitative Structure-Activity Relationship* |
| IF | 1.994 |
| 引用数 | 16 |
| 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) HSC-4(RCB1902) |