TY - JOUR T1 - Quantitative Structure–Cytotoxicity Relationship of Azulene Amide Derivatives JF - Anticancer Research JO - Anticancer Res SP - 3507 LP - 3518 DO - 10.21873/anticanres.13497 VL - 39 IS - 7 AU - KANA IMANARI AU - MASASHI HASHIMOTO AU - HIDETSUGU WAKABAYASHI AU - NORIYUKI OKUDAIRA AU - KENJIRO BANDOW AU - JUNKO NAGAI AU - MINEKO TOMOMURA AU - AKITO TOMOMURA AU - YOSHIHIRO UESAWA AU - HIROSHI SAKAGAMI Y1 - 2019/07/01 UR - http://ar.iiarjournals.org/content/39/7/3507.abstract N2 - 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. ER -