Evaluation of the in vitro and intracellular efficacy of new monosubstituted sulfonylureas against extensively drug-resistant tuberculosis
2012
Acetohydroxyacid synthase (AHAS) has been regarded as a potential drug target against Mycobacterium tuberculosis as it catalyses the first step in the pathway for biosynthesis of branched-chain amino acids. In our previous work, several monosubstituted sulfonylureas that are inhibitors of AHAS showed obvious in vitro activity against M. tuberculosis. In this study, further exploration of the antitubercular activity of newly synthesised monosubstituted sulfonylureas was conducted. A series of new compounds were identified that exhibit significant activity against in vitro and intracellular extensively drug-resistant M. tuberculosis. These results provide a further insight into the structural requirements for targeting AHAS to develop potential new agents to combat tuberculosis.
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