Kana Imanari1, Masashi Hashimoto1, Hidetsugu Wakabayashi2, Noriyuki Okudaira3, Kenjiro Bandow4, Junko Nagai5, Mineko Tomomura4, Akito Tomomura4, Yoshihiro Uesawa5, Hiroshi Sakagami6. 1. Faculty of Science, Josai University, Sakado, Japan. 2. Faculty of Science, Josai University, Sakado, Japan hwaka@josai.ac.jp sakagami@dent.meikai.ac.jp. 3. Division of Pharmacology, Meikai University School of Dentistry, Sakado, Japan. 4. Division of Biochemistry, Meikai University School of Dentistry, Sakado, Japan. 5. Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo, Japan. 6. Meikai University Research Institute of Odontology (M-RIO), Meikai University School of Dentistry, Sakado, Japan.
Abstract
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 [1-7], 7-isopropyl-3-methyl [8-14] or 2-methoxy group [15-21] Materials and Methods: Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC50) 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 CC50 value against OSCC cell lines. Apoptosis-inducing activity was evaluated by caspase-3 activation and appearance of subG1 cell population. RESULTS: [8-14] showed higher TS and PSE values, than [1-7] and [15-21] The most active compound [8-14] induced apoptosis in C9-22 OSCC cells at 4-times higher CC50 Quantitative structure-activity relationship analysis of [1-14] 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 [8] can be a potential candidate of lead compound for manufacturing new anticancer drug. Copyright
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 [1-7], 7-isopropyl-3-methyl [8-14] or 2-methoxy group [15-21] Materials and Methods:Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC50) 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 CC50 value against OSCC cell lines. Apoptosis-inducing activity was evaluated by caspase-3 activation and appearance of subG1 cell population. RESULTS: [8-14] showed higher TS and PSE values, than [1-7] and [15-21] The most active compound [8-14] induced apoptosis in C9-22 OSCC cells at 4-times higher CC50 Quantitative structure-activity relationship analysis of [1-14] 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 [8] can be a potential candidate of lead compound for manufacturing new anticancer drug. Copyright