Advances in mycobacterial isocitrate lyase targeting and inhibitors
Language English Country United Arab Emirates Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
23092127
DOI
10.2174/092986712804485782
PII: CMC-EPUB-20121017-1
Knihovny.cz E-resources
- MeSH
- Antitubercular Agents chemical synthesis chemistry metabolism MeSH
- Bacterial Proteins antagonists & inhibitors metabolism MeSH
- Fluoroquinolones chemical synthesis chemistry metabolism MeSH
- Enzyme Inhibitors chemical synthesis chemistry metabolism MeSH
- Isocitrate Lyase antagonists & inhibitors metabolism MeSH
- Mycobacterium tuberculosis enzymology MeSH
- Nucleotides chemistry metabolism MeSH
- Peptides chemistry metabolism MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Antitubercular Agents MeSH
- Bacterial Proteins MeSH
- Fluoroquinolones MeSH
- Enzyme Inhibitors MeSH
- Isocitrate Lyase MeSH
- Nucleotides MeSH
- Peptides MeSH
Isocitrate lyase plays a key role for survival of Mycobacterium tuberculosis in the latent form during a chronic stage of infection. This enzyme is important for M. tuberculosis during steady stage growth when it converts isocitrate to succinate and glyoxylate. Then, the glyoxylate is condensed with acetyl-CoA to form malate by malate synthase. The carbon conserving glyoxylate pathway has not been observed in mammals; therefore, it has been determined as a potential drug target for discovery of a new antituberculosis agent. Novel active molecules should shorten the duration of therapy, prevent resistance development and eliminate latent disease. The review summarizes recent progresses in isocitrate lyase inhibitors, overviews structural analogues of several metabolic intermediates (3-nitropropionate, 3-bromopyruvate, itaconate, itaconic anhydride), peptide inhibitors, and recently developed inhibitors with various chemical structures. The largest inhibitory activity against isocitrate lyase (IC(50) of 0.10 ± 0.01 μM) and concomitantly a significant antimycobacterial activity has been presented by fluoroquinolone derivative 1-cyclopropyl-7-[3,5-dimethyl-4-(3-nitropropanoyl)piperazin-1-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which has incorporated 3-nitropropionyl group as one of the structural analogue of succinate, a metabolic intermediate.
References provided by Crossref.org
Antibacterial activity of salicylanilide 4-(trifluoromethyl)-benzoates