In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria

Hosung Sohn, Kil Soo Lee, Young Kwan Ko, Jae Wook Ryu, Jae Choon Woo, Dong Wan Koo, Sung Jae Shin, Se Jin Ahn, A. Rum Shin, Chang Hwa Song, Eun Kyeong Jo, Jeong Kyu Park, Hwa Jung Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)567-571
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume31
Issue number6
DOIs
Publication statusPublished - 2008 Jun

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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