Reference - Detail
RRC ID | 54119 |
---|---|
Author | Shi H, Nagai J, Sakatsume T, Bandow K, Okudaira N, Sakagami H, Tomomura M, Tomomura A, Uesawa Y, Takao K, Sugita Y. |
Title | Quantitative Structure-Cytotoxicity Relationship of 2-(N-cyclicamino)chromone Derivatives. |
Journal | Anticancer Res |
Abstract |
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. |
Volume | 38(7) |
Pages | 3897-3906 |
Published | 2018-7-1 |
DOI | 10.21873/anticanres.12674 |
PII | 38/7/3897 |
PMID | 29970510 |
MeSH | Antineoplastic Agents / chemistry* Antineoplastic Agents / pharmacology* Apoptosis / drug effects Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / pathology Cell Cycle / drug effects Cell Line, Tumor Chromones / chemistry* Chromones / pharmacology* Drug Screening Assays, Antitumor Humans Mouth Neoplasms / drug therapy Mouth Neoplasms / pathology Quantitative Structure-Activity Relationship |
IF | 1.994 |
Times Cited | 5 |
Resource | |
Human and Animal Cells | HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) |