Toshiki Wada1, Ryota Maruyama1, Yuta Irie1, Masashi Hashimoto1, Hidetsugu Wakabayashi2, Noriyuki Okudaira3, Yoshihiro Uesawa4, Hajime Kagaya4, Hiroshi Sakagami5. 1. Faculty of Science, Josai University, Saitama, Japan. 2. Faculty of Science, Josai University, Saitama, Japan hwaka@josai.ac.jp sakagami@dent.meikai.ac.jp. 3. Division of Pharmacology, Meikai University School of Dentistry, Saitama, Japan. 4. Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan. 5. Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan hwaka@josai.ac.jp sakagami@dent.meikai.ac.jp.
Abstract
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. Copyright
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. Copyright