2. Academic Validation
  3. Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates

Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates

  • Bioorg Med Chem. 2014 Aug 1;22(15):4073-82. doi: 10.1016/j.bmc.2014.05.064.
Martin Krátký 1,  Marie Volková 2,  Eva Novotná 3,  František Trejtnar 4,  Jiřina Stolaříková 5,  Jarmila Vinšová 6
Affiliations

Affiliations

  • 1 Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: martin.kratky@faf.cuni.cz.
  • 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: marie.volkova@faf.cuni.cz.
  • 3 Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: eva.novotna@faf.cuni.cz.
  • 4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: frantisek.trejtnar@faf.cuni.cz.
  • 5 Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00 Ostrava, Czech Republic. Electronic address: Jirina.Stolarikova@zu.cz.
  • 6 Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: jarmila.vinsova@faf.cuni.cz.
PMID: 24953953 DOI: 10.1016/j.bmc.2014.05.064
Abstract

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.

Keywords

Antimicrobial activity; Antimycobacterial activity; Cytotoxicity; Isocitrate lyase inhibition; Salicylanilide carbamate; Salicylanilide thiocarbamate.

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