Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24953953
DOI
10.1016/j.bmc.2014.05.064
PII: S0968-0896(14)00423-4
Knihovny.cz E-resources
- Keywords
- Antimicrobial activity, Antimycobacterial activity, Cytotoxicity, Isocitrate lyase inhibition, Salicylanilide carbamate, Salicylanilide thiocarbamate,
- MeSH
- Anti-Infective Agents chemical synthesis chemistry pharmacology MeSH
- Hep G2 Cells MeSH
- Gram-Positive Bacteria drug effects MeSH
- Fungi drug effects MeSH
- Isocitrate Lyase antagonists & inhibitors metabolism MeSH
- Carbamates chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Methicillin-Resistant Staphylococcus aureus drug effects MeSH
- Microbial Sensitivity Tests MeSH
- Mycobacterium avium drug effects MeSH
- Mycobacterium kansasii drug effects MeSH
- Salicylanilides chemistry MeSH
- Thiocarbamates chemical synthesis chemistry pharmacology MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Infective Agents MeSH
- Isocitrate Lyase MeSH
- Carbamates MeSH
- salicylanilide MeSH Browser
- Salicylanilides MeSH
- Thiocarbamates 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.
References provided by Crossref.org
Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics
Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates
