Synergistic Action of Substituted Indole Derivatives and Clinically used Antibiotics Against Drug-Resistant Bacteria

Abstract

<b>Aim:</b> The current report describes the discovery of indole derivatives that synergize with standard antibiotics. <b>Materials & methods:</b> The antibacterial activities were determined using an optimized time-kill method, while viability of mammalian cells was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. <b>Results:</b> The synergy is observed with methicillin- and vancomycin-resistant <i>Staphylococcus aureus</i> bacterial strains, against which the standard antibiotics show no activities of their own. Our indole derivatives in combination with antibiotics lack toxicity toward mammalian cells, do not promote the evolution of resistance of <i>S. aureus</i> in comparison to clinically established antibiotics, and likely work by permeabilizing bacterial cell membranes. <b>Conclusion:</b> The above-mentioned findings demonstrate the potential clinical applications of our indole derivatives.