In vitro antibacterial and antifungal activity of salicylanilide pyrazine-2-carboxylates

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.