Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium tuberculosis strains, atypical mycobacteria and isocitrate lyase
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24333643
DOI
10.1016/j.ejps.2013.12.001
PII: S0928-0987(13)00458-2
Knihovny.cz E-zdroje
- Klíčová slova
- Antimycobacterial activity, In vitro activity, Isocitrate lyase inhibition, Multidrug-resistant tuberculosis, Pyrazine-2-carboxylic acid ester, Salicylanilide ester,
- MeSH
- antibakteriální látky farmakologie MeSH
- isocitrátlyasa antagonisté a inhibitory MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence MeSH
- Mycobacterium tuberculosis účinky léků genetika MeSH
- netuberkulózní mykobakterie účinky léků růst a vývoj MeSH
- pyrazinamid analogy a deriváty farmakologie MeSH
- salicylanilidy farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- isocitrátlyasa MeSH
- pyrazinamid MeSH
- pyrazinoic acid MeSH Prohlížeč
- salicylanilide MeSH Prohlížeč
- salicylanilidy MeSH
The development of antimicrobial agents represents an up-to-date topic. This study investigated in vitro antimycobacterial activity, mycobacterial isocitrate lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be considered being mutual prodrugs of both antimycobacterial active salicylanilides and pyrazinoic acid (POA), an active metabolite of pyrazinamide, in which these esters are likely hydrolysed without presence of pyrazinamidase/nicotinamidase. Minimum inhibitory concentrations (MICs) of the esters were within the range 0.5-8 μmol/l for Mycobacterium tuberculosis and 1-32 μmol/l for nontuberculous mycobacteria (Mycobacterium avium, Mycobacterium kansasii). All esters showed a weak inhibition (8-17%) of isocitrate lyase at the concentration of 10 μmol/l. The most active pyrazinoates showed MICs for multidrug-resistant tuberculosis strains in the range of 0.125-2 μmol/l and no cross-resistance with clinically used drugs, thus being the most in vitro efficacious salicylanilide esters with 4-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate superiority (MICs⩽0.25 μmol/l). This promising activity is likely due to an additive or synergistic effect of released POA and salicylanilides. Selectivity indexes for the most active salicylanilide pyrazinoates ranged up to 64, making some derivatives being attractive candidates for the next research; 4-bromo-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate showed the most convenient toxicity profile.
Citace poskytuje Crossref.org
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