title: In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria.
abstract: Sulfometuron methyl (SM) is an inhibitor of acetohydroxyacid synthase (AHAS), the first common enzyme in the branched-chain amino acid biosynthetic pathway, and shows activity against Mycobacterium tuberculosis both in vitro and in vivo. To develop AHAS inhibitor derivatives with more potent activity, 100 sulfonylurea analogues were screened for antimycobacterial activity against M. tuberculosis and non-tuberculous mycobacteria (NTM), and then evaluated for intracellular activity using mouse macrophages. Three new compounds with antimycobacterial activity comparable with that of SM were identified. These compounds exhibit significant activity against intracellular M. tuberculosis (including the drug-resistant M. tuberculosis strains), and NTM Mycobacterium abscessus and Mycobacterium kansasii, respectively.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-Dong, Jung-Ku, Daejeon 301-747, South Korea.
authors.forename: Hosung
authors.initials: H
authors.lastname: Sohn
authors.forename: Kil-Soo
authors.initials: KS
authors.lastname: Lee
authors.forename: Young-Kwan
authors.initials: YK
authors.lastname: Ko
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ryu
authors.forename: Jae-Choon
authors.initials: JC
authors.lastname: Woo
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Koo
authors.forename: Sung-Jae
authors.initials: SJ
authors.lastname: Shin
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Ahn
authors.forename: A-Rum
authors.initials: AR
authors.lastname: Shin
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013453:Sulfonylurea Compounds; D000095:Acetolactate Synthase