Advances in mycobacterial isocitrate lyase targeting and inhibitors
Jazyk angličtina Země Spojené arabské emiráty Médium print
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
23092127
DOI
10.2174/092986712804485782
PII: CMC-EPUB-20121017-1
Knihovny.cz E-zdroje
- MeSH
- antituberkulotika chemická syntéza chemie metabolismus MeSH
- bakteriální proteiny antagonisté a inhibitory metabolismus MeSH
- fluorochinolony chemická syntéza chemie metabolismus MeSH
- inhibitory enzymů chemická syntéza chemie metabolismus MeSH
- isocitrátlyasa antagonisté a inhibitory metabolismus MeSH
- Mycobacterium tuberculosis enzymologie MeSH
- nukleotidy chemie metabolismus MeSH
- peptidy chemie metabolismus MeSH
- vazba proteinů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antituberkulotika MeSH
- bakteriální proteiny MeSH
- fluorochinolony MeSH
- inhibitory enzymů MeSH
- isocitrátlyasa MeSH
- nukleotidy MeSH
- peptidy 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.
Citace poskytuje Crossref.org
Antibacterial activity of salicylanilide 4-(trifluoromethyl)-benzoates