Antituberculosis agents - II. Evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole derivatives

Using the radiometric BACTEC 460-TB methodology, the minimum inhibitory concentration (MIC) of a series of 2-(1-methyl-5-nitro-2-imidazolyl-1,3,4-thiadiazole'-5-alkylsulfides, alkylsulfoxides and alkylsulfones which had been reported previously as antifungal agents, were determined. Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. The results indicate that compounds bearing a primary alkylthio substitution displayed good antituberculosis activity (MIC 3.13-6.25 mug/ml). Oxidation to sulfone abolished the antituberculosis activity in methyl and propyl derivatives while the ethylsulfonyl analogue was active (MIC = 1.56 mug/ml). The cytotoxic effects indicate that 2-(1-methyl-5-nitro-2-imidazolyl)-5-methylthio-1,3,4-thiadiazole was the least toxic compound (IC(50) > 10 mug/ml). Generally, all compounds showed a low selectivity index. (C) 2001 Elsevier Science S.A. All rights reserved.