Quantitative Structure-Cytotoxicity Relationship of Azulene Amide Derivatives.

Background/aim: Very few studies of anticancer activity of azulene amides led us to investigate the cytotoxicity of 21 N-alkylazulene-1-carboxamides introduced either with 3-methyl , 7-isopropyl-3-methyl or 2-methoxy group Materials and Methods: Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC) against three normal human oral mesenchymal cells to that against four human oral squamous cell carcinoma (OSCC) cell lines. Potency-selectivity expression (PSE) was calculated by dividing TS value by CC value against OSCC cell lines. Apoptosis-inducing activity was evaluated by caspase-3 activation and appearance of subG cell population.

Results: showed higher TS and PSE values, than and The most active compound induced apoptosis in C9-22 OSCC cells at 4-times higher CC Quantitative structure-activity relationship analysis of demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the molecular shape and hydrophobicity.

Conclusion: 7-Isopropyl-3-methyl-N-propylazulene-1-carboxamide can be a potential candidate of lead compound for manufacturing new anticancer drug.