title: Evaluation of the in vitro and intracellular efficacy of new monosubstituted sulfonylureas against extensively drug-resistant tuberculosis.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, The 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Lei
authors.forename: Xianghong
authors.initials: X
authors.lastname: Meng
authors.forename: Jufang
authors.initials: J
authors.lastname: He
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D054908:Extensively Drug-Resistant Tuberculosis / Q000382:microbiology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013453:Sulfonylurea Compounds