Quantitative Structure-Cytotoxicity Relationship of 3-Styryl-2H-chromenes.
BACKGROUND
Sixteen 3-styryl-2H-chromenes were subjected to quantitative structure-activity relationship analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to find their new biological activities.


MATERIALS AND METHODS
Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines, three mesenchymal and two epithelial normal oral cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-selectivity (TS) was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal human oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Potency-selectivity expression (PSE) was determined by the ratio of TS/CC50 against OSCC. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method.


RESULTS
All 3-styryl-2H-chromene derivatives showed relatively high tumor selectivity. Especially, the compound that has a methoxy group at 7-position of the chromene ring and chlorine at 4'-position of phenyl group in styryl moiety [ 12: ] showed the highest TS and PSE values, exceeding those of resveratrol, doxorubicin and 5-FU. All compounds showed no anti-HIV activity. Among 330 chemical descriptors, 8, 74 and 16 descriptors significantly correlated to the cytotoxicity of normal and tumor cells, and tumor-specificity, respectively.


CONCLUSION
Multivariate statistics with chemical descriptors for molecular shape and flatness may be useful for the evaluation of tumor-specificity of 3-styryl-2H-chromenes.
['Uesawa|Yoshihiro|Y|', 'Sakagami|Hiroshi|H|', 'Ishihara|Mariko|M|', 'Kagaya|Hajime|H|', 'Kanamoto|Taisei|T|', 'Terakubo|Shigemi|S|', 'Nakashima|Hideki|H|', 'Yahagi|Hideaki|H|', 'Takao|Koichi|K|', 'Sugita|Yoshiaki|Y|']
D019380:Anti-HIV Agents D000970:Antineoplastic Agents D002460:Cell Line D002867:Chromones D006801:Humans D015394:Molecular Structure D021281:Quantitative Structure-Activity Relationship
3-styryl-2H-chromenes cytotoxicity tumor selectivity anti-HIV activity QSAR analysis