Antistaphylococcal Activity of Novel Salicylanilide Derivatives

Annmarie      Mollaghan; Jarmila      Vinsova; Ales      Imramovsky; Lesley      Cotter; Brigid      Lucey; Jim      O'Mahony; Aisling      Costelloe; Aidan      Coffey

Abstract

This study examined the antibacterial properties of nineteen benzoxazole, isoniazid, ethionamide and salicylanilide derivatives against Staphylococcus aureus (S. aureus). It was found that three salicylanilide-derived compounds demonstrated antistaphylococcal activity: 5-Chloro-2-hydroxy-N-(4-(trifluoromethyl)phenyl)benzamide (5-Cl-4-CF3- SAL), 4-chloro-2-(3-chlorophenylcarbamyoyl)phenyl)-2-(benzyloxycarbonylamino)propanoate (AIM31) and 4-chloro-2- (4-(trifluoromethyl)phenylcarbamoyl)phenyl acetate (AIM33). Investigation of the chemical structures of these three compounds and comparison with a non-inhibitory salicylanilide compound (i.e. 5,3-diCl-SAL) illustrated that different combinations of chemical groups at defined positions on the salicylanilide core structure had a marked influence on antistaphylococcal activity. The most effective compound was AIM33 which inhibited staphylococcal growth and displayed an initial MIC value of 3.12 μg ml-1 and subsequent investigation revealed that an MIC as low as of 0.5 μg ml-1 was achievable. In this case, the dual presence of a trifluoromethyl group and an acetylated phenolic hydroxyl to the salicylanilide core structure led to greatly enhanced activity.

Keywords: Antimicrobial resistance, chemotherapeutic agents, MRSA, salicylanilide, Staphylococcus aureus, anti-staphylococcal drugs, Antistaphylococcal Activity, nosocomial pathogens, benzoxazole