Antimicrobial activity of 1,3,4-oxadiazole derivatives against planktonic cells and biofilm of Staphylococcus aureus

Future Med Chem. 2018 Feb;10(3):283-296. doi: 10.4155/fmc-2017-0159. Epub 2018 Jan 15.

Abstract

Aim: Staphylococcus aureus is a major cause of severe hospital-acquired infections, and biofilm formation is an important part of staphylococcal pathogenesis. Therefore, developing new antimicrobial agents against both planktonic cells and biofilm of S. aureus is a major challenge.

Results: Three 1,3,4-oxadiazole derivatives exhibited antimicrobial activity against seven S. aureus strains in vitro, with minimum inhibitory concentrations ranging from 4 to 32 μg/ml. At 4 × minimum inhibitory concentration, all compounds killed cells within 24 h, demonstrating bactericidal activity. In addition to their effects against planktonic cells, these compounds prevented biofilm formation in a dose-dependent manner, with inhibitory concentrations for biofilm formation ranging from 8 to 32 μg/ml. Interestingly, higher concentrations of these compounds were effective against mature biofilms and all compounds downregulated the transcription of the biofilm-related gene spa.

Conclusion: We report three new 1,3,4-oxadiazole derivatives that have bactericidal activity and could provide as alternatives to combat S. aureus.

Keywords: 1,3,4-oxadiazole derivatives; Staphylococcus aureus; antibiotic resistance; biofilm; planktonic cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Plankton / cytology
  • Plankton / drug effects*
  • Staphylococcus aureus / cytology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Oxadiazoles
  • 1,3,4-oxadiazole