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 microg/ml). Oxidation to sulfone abolished the antituberculosis activity in methyl and propyl derivatives while the ethylsulfonyl analogue was active (MIC = 1.56 microg/ml). The cytotoxic effects indicate that 2-(1-methyl-5-nitro-2-imidazolyl)-5-methylthio-1,3,4-thiadiazole was the least toxic compound (IC50 > 10 microg/ml). Generally, all compounds showed a low selectivity index.
Foroumadi
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Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Iran.
Mirzaei
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M
Shafiee
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D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
D000995:Antitubercular Agents; D013830:Thiadiazoles