Bio-evaluation of fluoro and trifluoromethyl-substituted salicylanilides against multidrug-resistant .

Methicillin-resistant (MRSA) and vancomycin-resistant (VRSA) are primary causes of skin and soft tissue infections worldwide. To address the emergency caused due to increasing multidrug-resistant (MDR) bacterial infections, a series of novel fluoro and trifluoromethyl-substituted salicylanilide derivatives were synthesized and their antimicrobial activity was investigated. MIC data reveal that the compounds inhibited specifically (MIC 0.25-64 µg/mL). The in vitro cytotoxicity of compounds with MIC < 1 µg/mL against Vero cells led to identification of four compounds (, , and ) with selectivity index above 10. These four compounds were tested against MDR panel. Remarkably, 5-chloro--(4'-bromo-3'-trifluoromethylphenyl)-2-hydroxybenzamide () demonstrated excellent activity against nine MRSA and three VRSA strains with MIC 0.031-0.062 µg/mL, which is significantly better than the control drugs methicillin and vancomycin. The comparative time-kill kinetic experiment revealed that the effect of bacterial killing of is comparable with vancomycin. Compound did not synergize with or antagonize any FDA-approved antibiotic and reduced pre-formed biofilm better than vancomycin. Overall, study suggested that could be further developed as a potent anti-staphylococcal therapeutic.