Synthesis and biological evaluation of indole-based peptidomimetics as antibacterial agents against Gram-positive bacteria

The emergence of bacterial multidrug resistance and the lack of new antimicrobial agents urgently demand the discovery and development of novel antibacterials that avoid bacterial resistance. Antimicrobial peptidomimetics represent a promising approach for overcoming antibiotic resistance. Herein we report the synthesis and evaluation of indole-based amphiphilic antimicrobial peptidomimetics, bearing hydrophobic side chains and hydrophilic cationic moieties. Among these derivatives, compound 28 demonstrated potent antimicrobial activity against Gram-positive bacteria, low hemolytic activity and low toxicity towards mammalian cells, as well as good stability in salt conditions. Moreover, compound 28 showed the rapid killing of bacteria via membrane-targeting action without developing bacterial resistance. More importantly, compound 28 displayed high antimicrobial potency against Gram-positive bacteria in a murine model of bacterial keratitis, and was found to be more efficient than vancomycin. Thus, compound 28 had great potential as a promising lead compound for the treatment of Gram-positive bacterial infection. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

The emergence of bacterial multidrug resistance and the lack of new antimicrobial agents have led to the urgent need for the discovery and development of novel antibacterials. Antimicrobial peptidomimetics have shown promise in overcoming antibiotic resistance and are effective in rapidly killing bacteria without inducing resistance. Specific compounds have demonstrated potent activity against Gram-positive bacteria, low toxicity to mammalian cells, good stability, and high efficacy in treating bacterial infections.