Reference - Detail
|Author||Sakagami H, Masuda Y, Tomomura M, Yokose S, Uesawa Y, Ikezoe N, Asahara D, Takao K, Kanamoto T, Terakubo S, Kagaya H, Nakashima H, Sugita Y.|
|Title||Quantitative Structure-Cytotoxicity Relationship of Chalcones.|
BACKGROUND:Fifteen chalcones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor specificity, in order to find their new biological activities.
MATERIALS AND METHODS:Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal cells to that against tumor cell lines. Potency-selectivity expression (PSE) value was calculated by dividing TS by CC50 against tumor cells. Apoptosis markers were detected by western blot analysis. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization.
RESULTS:Among 15 chalcone derivatives, (2E)-1-(2,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one had the highest TS and PSE values, comparable with those of doxorubicin and methotrexate, respectively. This compound also stimulated the cleavage of poly(ADP-ribose) polymerase and caspase-3. Chalone TS values were correlated with molecular shape and polarization rather than the types of substituted groups. None of the compounds had any anti-HIV activity.
CONCLUSION:Chemical modification of the lead compound may be a potential choice for designing new types of anticancer drugs.
|MeSH||Anti-HIV Agents / chemistry Antineoplastic Agents / chemistry* Apoptosis Carcinoma, Squamous Cell / drug therapy Cell Line, Tumor Chalcones / chemistry* Child Doxorubicin / chemistry Drug Screening Assays, Antitumor Epithelial Cells / drug effects Female Hep G2 Cells Humans Mesoderm / cytology Methotrexate / chemistry Mouth Neoplasms / drug therapy Quantitative Structure-Activity Relationship|
|Human and Animal Cells||Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902)|