RRC ID 54124
著者 Shi H, Nagai J, Sakatsume T, 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 3-(N-Cyclicamino)chromone Derivatives.
ジャーナル Anticancer Res
Abstract BACKGROUND/AIM:4H-1-Benzopyran-4-ones (chromones) provide a backbone structure for the chemical synthesis of potent anticancer drugs. In contrast to 2-(N-cyclicamino)chromones, the biological activity of 3-(N-cyclicamino)chromones has not been reported. In this study, cytotoxicity of 15 3-(N-cyclicamino)chromone derivatives was investigated and subjected to quantitative structure-activity relationship (QSAR) analysis.
MATERIALS AND METHODS:Cytotoxicity against four human oral squamous cell carcinoma cell lines and three 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 mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human oral squamous cell carcinoma 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 3,096 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using CORINA.
RESULTS:3-(4-phenyl-1-piperazinyl)-4H-1-benzopyran-4-one (3a) had the highest tumor specificity, comparable with that of melphalan, without induction of apoptosis. Compound 3a caused cytostatic growth inhibition and had much lower cytotoxicity against human oral keratinocytes compared to doxorubicin. TS of the 15 3-(N-cyclicamino)chromones was correlated with 3D structure and lipophilicity.
CONCLUSION:Chemical modification of 3a may be a potential choice for designing a new type of anticancer drug.
巻・号 38(8)
ページ 4459-4467
公開日 2018-8-1
DOI 10.21873/anticanres.12748
PII 38/8/4459
PMID 30061210
MeSH Antineoplastic Agents / chemistry* Antineoplastic Agents / pharmacology* Apoptosis / drug effects Carcinoma, Squamous Cell / drug therapy Cell Cycle / drug effects Cell Line Cell Line, Tumor Chromones / chemistry* Chromones / pharmacology* Doxorubicin / pharmacology Humans Keratinocytes / drug effects Mouth Neoplasms / drug therapy Quantitative Structure-Activity Relationship
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) HSC-3(RCB1975) HSC-4(RCB1902)