In Vitro Antibacterial and Antifungal Activity of Salicylanilide Pyrazine-2- carboxylates

Martin      Kratky; Jarmila      Vinsova; Vladimir      Buchta

Abstract

The development of new antimicrobial agents for the treatment of infectious diseases remains challenging due to the increasing impact of antibiotic resistance. Since salicylanilides and esters of pyrazine-2-carboxylic acid have been described as potential antimicrobials, we have designed and synthesized a series of 2-(phenylcarbamoyl)phenyl pyrazine-2-carboxylates. These were evaluated in vitro for the activity against fungi and Gram-positive and Gram-negative bacteria. All derivatives showed significant antibacterial activity against Gram-positive strains (MIC ≥ 0.98 µmol/L) including methicillin-resistant Staphylococcus aureus. The most active molecule was 5-chloro-2-(3-chlorophenylcarbamoyl)phenyl pyrazine-2-carboxylate. With one exception these esters were at least partly active against fungi tested strains, in particular against mould strains (MIC ≥ 1.95 µmol/L). The most active antifungal agent overall proved to be 2-(4-bromophenylcarbamoyl)-4-chlorophenyl pyrazine-2-carboxylate.

Keywords: Antibacterial activity, antifungal activity, in vitro activity, pyrazine-2-carboxylic acid ester, salicylanilide, salicylanilide ester, salicylanilide, Clostridium difficile, Staphylococcus aureus, MRSA, fungal pathogens