Background/aim: There exist few research articles regarding the anticancer activity of azulene-related compounds. We investigated here the relative cytotoxicity of 10 azulene amide derivatives against cancer and normal cells.
Materials and methods: Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells (gingival fibroblasts, periodontal ligament fibroblasts and pulp cells) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide method. Antitumor activity was evaluated by tumor-specificity (TS) (ratio of mean 50% cytotoxic concentration (CC50) against normal cells to that against OSCC cell lines) and potency-selectivity expression (PSE) (ratio of TS to CC50 against tumor cells). Apoptosis-inducing activity was evaluated by cleavage of poly ADP-ribose polymerase and caspase-3 with western blot analysis.
Results: N-Propylguaiazulenecarboxamide [1] showed the highest TS and PSE values, compared to that of doxorubicin, and induced apoptosis in two OSCC cell lines. QSAR analysis demonstrated that their tumor-specificity of azulene amide derivatives was correlated with hydrophobicity and molecular shape.
Conclusion: Compound [1] can be considered as a lead compound for manufacturing new anticancer drug candidates.
Keywords: Azulene amides; apoptosis; cytotoxicity; hydrophobicity; molecular shape; tumor specificity.
Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.