論文 - 詳細
| RRC ID | 51904 |
|---|---|
| 著者 | Uesawa Y, Sakagami H, Kagaya H, Yamashita M, Takao K, Sugita Y. |
| タイトル | Quantitative Structure-cytotoxicity Relationship of 3-Benzylidenechromanones. |
| ジャーナル | Anticancer Res |
| Abstract |
AIM:Sixteen 3-benzylidenechromanones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor-specificity, in order to examine their new biological activities. MATERIALS AND METHODS:Cytotoxicity against two human oral squamous cell carcinoma cell lines, two mesenchymal and two epithelial normal oral 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 CC50 (50% cytotoxic concentration) against normal cells to that against tumor cell lines. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method. RESULTS:3-Benzylidenechromanone derivatives that have a methoxy group at 7-position of the chromanone ring and hydroxyl or methoxy group at 4'-position of benzene ring showed relatively higher TS values, exceeding those of doxorubicin (DXR) and 5-fluorouracil (5-FU). Since these anticancer drugs were highly cytotoxic to normal keratinocytes, QSAR analysis was performed with oral carcinoma and mesenchymal normal cells. Tumor-specificity was well correlated with 3D-MoRSE descriptors (that relate to three dimensional shapes) and Edge adjacency indices (that relate to two dimensional shapes and polarization). Introduction of hydroxyl group at 3'-position of benzene ring significantly elevated the tumor-specificity. CONCLUSION:Molecular shape, size and polarization are useful markers for the evaluation of tumor-specificity of 3-benzylidenechromanone derivatives. |
| 巻・号 | 36(11) |
| ページ | 5803-5812 |
| 公開日 | 2016-11-1 |
| DOI | 10.21873/anticanres.11164 |
| PII | 36/11/5803 |
| PMID | 27793902 |
| MeSH | Carcinoma, Squamous Cell / pathology Cell Line, Tumor Drug Screening Assays, Antitumor Humans Isoflavones / chemistry* Isoflavones / pharmacology* Quantitative Structure-Activity Relationship |
| IF | 1.994 |
| 引用数 | 8 |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) |