Anti-biofilm and anti-adherence properties of novel cyclic dipeptides against oral pathogens

Bioorg Med Chem. 2019 Jun 15;27(12):2323-2331. doi: 10.1016/j.bmc.2018.11.042. Epub 2018 Nov 29.

Abstract

Microorganisms embedded in a biofilm are significantly more resistant to antimicrobial agents and the defences of the human immune system, than their planktonic counterpart. Consequently, compounds that can inhibit biofilm formation are of great interest for novel therapeutics. In this study, a screening approach was used to identify novel cyclic dipeptides that have anti-biofilm activity against oral pathogens. Five new active compounds were identified that prevent biofilm formation by the cariogenic bacterium Streptococcus mutans and the pathogenic fungus Candida albicans. These compounds also inhibit the adherence of microorganisms to a hydroxylapatite surface. Further investigations were conducted on these compounds to establish the structure-activity relationship, and it was deduced that the common cleft pattern is required for these molecules to act effectively against biofilms.

Keywords: Adherence; Anti-biofilm; Biofilm; C. albicans; Candidiasis; Cyclic dipeptides; Dental caries; Quorum sensing; S. mutans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Bacterial Adhesion / drug effects*
  • Biofilms / drug effects*
  • Candida albicans / drug effects
  • Candida albicans / physiology
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Streptococcus mutans / drug effects
  • Streptococcus mutans / physiology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Dipeptides
  • Peptides, Cyclic