Synthesis of new triazole fused imidazo[2,1-b]thiazole hybrids with emphasis on Staphylococcus aureus virulence factors

Bioorg Med Chem Lett. 2019 Oct 1;29(19):126621. doi: 10.1016/j.bmcl.2019.08.025. Epub 2019 Aug 12.

Abstract

A series of new triazole fused imidazo[2,1-b]thiazole hybrids (9a-u) were designed, synthesized and evaluated as antimicrobial agents. Compounds 9c, 9d, 9e, 9j and 9l showed promising broad spectrum antimicrobial activity. Further, compound 9c exhibited significant anti-biofilm activity with single and mixed biofilm disruption demonstrated by Field Emission Scanning Electron Microscope (FE-SEM). Furthermore, molecular docking studies revealed that they interact with the virulence factor, Staphylococcus aureus dehydrosqualene synthase (CrtM) (PDB ID: 2ZCS). Overall, the findings suggest compound 9c as potential lead for further development of novel antibacterial and anti-biofilm agents.

Keywords: Antimicrobial; Fused; Imidazo[2,1-b]thiazole; Staphylococcus aureus; Triazole; Virulence factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Molecular Docking Simulation
  • Molecular Structure
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship
  • Thiazoles / chemistry*
  • Triazoles / chemistry*
  • Virulence Factors / metabolism*

Substances

  • Anti-Bacterial Agents
  • Thiazoles
  • Triazoles
  • Virulence Factors