論文 - 詳細
| RRC ID | 54123 |
|---|---|
| 著者 | Nagai J, Shi H, Kubota Y, Bandow K, Okudaira N, Uesawa Y, Sakagami H, Tomomura M, Tomomura A, Takao K, Sugita Y. |
| タイトル | Quantitative Structure-Cytotoxicity Relationship of Pyrano[4,3-b]chromones. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:4H-1-Benzopyran-4-one (chromone) provides a backbone structure for the chemical synthesis of potent anticancer drugs. Since studies of the biological activity of pyrano[4,3-b]chromones are limited, we investigated a total of 20 pyrano[4,3-b]chromones (10 sets of diastereomers) for their cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and human normal oral cells, and then carried out a quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS:Cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-specificity (TS) was evaluated by the ratio of mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human OSCC cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by the CC50 against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,072 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using CORINA. RESULTS:8-Chloro-4,4a-dihydro-3-methoxy-3-methyl-3H,10H-pyrano[4,3-b][1]benzopyran-10-one (16) and 3-ethoxy-4,4a-dihydro-8-methoxy-3H,10H-pyrano[4,3-b][1]benzopyran-10-one (17) had the highest TS, higher than that of 5-flurouracil and melphalan, without induction of apoptosis. Compound 16 induced cytostatic growth inhibition and much lower cytotoxicity against human normal oral keratinocytes compared to doxorubicin. TS of 20 pyrano[4,3-b]chromones was correlated with 3D structure, polarity, ionic potential and electric state. CONCLUSION:Chemical modification of 16 may be a potential choice for designing a new type of anticancer drug. |
| 巻・号 | 38(8) |
| ページ | 4449-4457 |
| 公開日 | 2018-8-1 |
| DOI | 10.21873/anticanres.12747 |
| PII | 38/8/4449 |
| PMID | 30061209 |
| MeSH | Antineoplastic Agents / chemistry* Antineoplastic Agents / pharmacology* Apoptosis / drug effects Carcinoma, Squamous Cell / drug therapy Cell Line Cell Line, Tumor Child Chromones / chemistry* Chromones / pharmacology* Doxorubicin / pharmacology Female Humans Mouth Neoplasms / drug therapy Quantitative Structure-Activity Relationship |
| IF | 1.994 |
| 引用数 | 7 |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) HSC-2(RCB1945) |