Preventing Candida albicans biofilm formation using aromatic-rich piperazines

Bioorg Med Chem. 2020 Dec 1;28(23):115810. doi: 10.1016/j.bmc.2020.115810. Epub 2020 Oct 9.

Abstract

The global increase in microbial resistance is an imminent threat to public health. Effective treatment of infectious diseases now requires new antimicrobial therapies. We report herein the discovery of aromatic-rich piperazines that inhibit biofilm formation by C. albicans. 22 piperazines, including 16 novel ones, were prepared efficiently using a combination of solid- and solution phase synthesis. The most potent compound prevents morphological switching under several hypha-inducing conditions and reduces C. albicans' ability to adhere to epithelial cells. These processes are essential to the development of Candida biofilms, which are associated with its increased resistance to immune defenses and antifungal agents.

Keywords: Antibiofilm; Candida albicans; Morphological switching; Oxime resin; Piperazines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Biofilms / drug effects*
  • Candida albicans / physiology*
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology

Substances

  • Antifungal Agents
  • Piperazines