RT Journal Article SR Electronic T1 Quantitative Structure–Cytotoxicity Relationship of 2-(N-cyclicamino)chromone Derivatives JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3897 OP 3906 DO 10.21873/anticanres.12674 VO 38 IS 7 A1 HAIXIA SHI A1 JUNKO NAGAI A1 TSUKASA SAKATSUME A1 KENJIRO BANDOW A1 NORIYUKI OKUDAIRA A1 HIROSHI SAKAGAMI A1 MINEKO TOMOMURA A1 AKITO TOMOMURA A1 YOSHIHIRO UESAWA A1 KOICHI TAKAO A1 YOSHIAKI SUGITA YR 2018 UL http://ar.iiarjournals.org/content/38/7/3897.abstract AB Background/Aim: 4H-1-Benzopyran-4-ones (chromones) have provided backbone structure for the chemical synthesis of potent anticancer drugs. In this study, the cytotoxicity of fifteen 2-(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 by 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 CC50 against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,089 physicochemicals, structural and quantum chemical features were calculated from the most stabilized structure optimized using Corina. Results: 7-Methoxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one (5c) showed highest tumor-specificity, comparable with that of doxorubicin, without inducing apoptosis. Tumor-specificity of fifteen 2-(N-cyclicamino) chromones was correlated with molecular shape, especially 3D-structure. Conclusion: Chemical modification of 5c may be a potential choice for designing a new type of anticancer drugs.