INFLUENCE OF 2-(4-AMINOPHENYL)BENZOTHIAZOLES ON GROWTH OF HUMAN OVARIAN-CARCINOMA CELLS IN-VITRO AND IN-VIVO

2-(4-Aminophenyl)benzothiazole molecules substituted in the 3 position of the phenyl ring with a halogen atom or methyl moiety compromise a group of compounds that potently inhibit specific human ovarian carcin oma cell lines. GI(50) values fall within the nM range. Inhibition is highly selective - whereas the GI(50) value in IGROV1 cells consistent ly lies at < 10 nM, SK-OV-3 presents GI(50) values > 10 mu M. Biphasic dose-response relationships were observed in sensitive cell lines aft er 48-h drug exposure. COMPARE analyses revealed the very similar prof iles of anti-tumour activity of 3-substituted benzothiazoles and 5-(4- dimethylaminophenylazo)quinoline, with Pearson correlation coefficient s > 0.65. Anti-tumour activity extended to preliminary in vivo tests. The growth of OVCAR-3 cells in polyvinylidene fluoride (PVDF) hollow f ibres implanted in the peritoneal cavity of mice was inhibited by more than 50% after intraperitoneal (i.p.) administration of 2-(4-amino-3- methylphenyl)benzothiazole (10 mg kg(-1)), 2-(4-amino-3-chlorophenyl)b enzothiazole (100 mg kg(-1)) or 2-(4-amino-3-bromophenyl)benzothiazole (150 mg kg(-1)). The growth of OVCAR-3 tumours in subcutaneously (s.c .) implanted hollow fibres was retarded by more than 50% after treatme nt with 2-(4-amino-3-methylphenyl)benzothiazole (6.7 and 10 mg kg(-1)) . In addition, the growth of s.c. OVCAR-3 xenografts was delayed after exposure to DF 203. However, the relationship between drug concentrat ion and growth inhibition was inverse.