Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents

Abstract

Series of <i>N</i>-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) agents from a molecular hybridization approach. The representative compound <b>19</b> showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable <i>in vitro</i> activities to that of vancomycin. Moreover, compound <b>19</b> also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant <i>Enterococcus faecalis</i> (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound <b>19</b> was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new <i>N</i>-substituted carbazoles as potential anti-MRSA agents.