New Application of Neomycin B-Bisbenzimidazole Hybrids as Antifungal Agents

Nishad Thamban Chandrika, Sanjib K. Shrestha, Nihar Ranjan, Anindra Sharma, Dev P. Arya, Sylvie Garneau-Tsodikova

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Alkylated aminoglycosides and bisbenzimidazoles have previously been shown to individually display antifungal activity. Herein, we explore for the first time the antifungal activity (in liquid cultures and in biofilms) of ten alkylated aminoglycosides covalently linked to either mono-or bisbenzimidazoles. We also investigate their toxicity against mammalian cells, their hemolytic activity, and their potential mechanism(s) of action (inhibition of fungal ergosterol biosynthetic pathway and/or reactive oxygen species (ROS) production). Overall, many of our hybrids exhibited broad-spectrum antifungal activity. We also found them to be less cytotoxic to mammalian cells and less hemolytic than the FDA-Approved antifungal agents amphotericin B and voriconazole, respectively. Finally, we show with our best derivative (8) that the mechanism of action of our compounds is not the inhibition of ergosterol biosynthesis, but that it involves ROS production in yeast cells.

Original languageEnglish
Pages (from-to)196-207
Number of pages12
JournalACS Infectious Diseases
Volume4
Issue number2
DOIs
StatePublished - Feb 9 2018

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

Keywords

  • benzimidazoles
  • biofilm
  • cytotoxicity
  • ergosterol
  • hemolysis
  • reactive oxygen species (ROS)
  • time-kill

ASJC Scopus subject areas

  • Infectious Diseases

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