Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24953953
DOI
10.1016/j.bmc.2014.05.064
PII: S0968-0896(14)00423-4
Knihovny.cz E-zdroje
- Klíčová slova
- Antimicrobial activity, Antimycobacterial activity, Cytotoxicity, Isocitrate lyase inhibition, Salicylanilide carbamate, Salicylanilide thiocarbamate,
- MeSH
- antiinfekční látky chemická syntéza chemie farmakologie MeSH
- buňky Hep G2 MeSH
- grampozitivní bakterie účinky léků MeSH
- houby účinky léků MeSH
- isocitrátlyasa antagonisté a inhibitory metabolismus MeSH
- karbamáty chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium účinky léků MeSH
- Mycobacterium kansasii účinky léků MeSH
- salicylanilidy chemie MeSH
- thiokarbamáty chemická syntéza chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiinfekční látky MeSH
- isocitrátlyasa MeSH
- karbamáty MeSH
- salicylanilide MeSH Prohlížeč
- salicylanilidy MeSH
- thiokarbamáty MeSH
The development of novel antimicrobial drugs represents a cutting edge research topic. In this study, 20 salicylanilide N,N-disubstituted carbamates and thiocarbamates were designed, synthesised and characterised by IR, (1)H NMR and (13)C NMR. The compounds were evaluated in vitro as potential antimicrobial agents against Mycobacterium tuberculosis and nontuberculous mycobacteria (Mycobacterium avium and Mycobacterium kansasii) as well as against eight bacterial and fungal strains. Additionally, we investigated the inhibitory effect of these compounds on mycobacterial isocitrate lyase and cellular toxicity. The minimum inhibitory concentrations (MICs) against mycobacteria were from 4 μM for thiocarbamates and from 16 μM for carbamates. Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, were inhibited with MICs from 0.49 μM by thiocarbamates, whilst Gram-negative bacteria and most of the fungi did not display any significant susceptibility. All (thio)carbamates mildly inhibited isocitrate lyase (up to 22%) at a concentration of 10 μM. The (thio)carbamoylation of the parent salicylanilides led to considerably decreased cytotoxicity and thus improved the selectivity indices (up to 175). These values indicate that some derivatives are attractive candidates for future research.
Citace poskytuje Crossref.org
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