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

Farmaco. 2001 Aug;56(8):621-3. doi: 10.1016/s0014-827x(01)01099-0.

Abstract

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.

MeSH terms

  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Chlorocebus aethiops
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*
  • Vero Cells

Substances

  • Antitubercular Agents
  • Thiadiazoles