Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of <i>Enterococcus faecalis</i>

Abstract

A series of isopropanol-bridged carbazole azoles as potential antimicrobial agents were designed and synthesized from commercial carbazoles. Bioassay revealed that 3,6-dichlorocarbazolyl triazole <b>3f</b> could effectively inhibit the growth of <i>E. faecalis</i> with minimal inhibitory concentration of 2 μg/mL. The active molecule <b>3f</b> showed lower propensity to trigger the development of resistance in bacteria than norfloxacin and exerted rapidly bactericidal ability. Compound <b>3f</b> also exhibited low cytotoxicity to normal mammalian RAW264.7 cells. Further mechanism exploration indicated that conjugate <b>3f</b> was membrane active against <i>E. faecalis</i> and could form <b>3f</b>-DNA complex by intercalating into DNA of resistant <i>E. faecalis</i>, which might be responsible for its antimicrobial action. Molecular docking showed an efficient binding of triazole derivative <b>3f</b> with DNA gyrase enzyme through noncovalent interactions.