Synthesis of Chimeric Thiazolo-Nootkatone Derivatives as Potent Antimicrobial Agents

ChemMedChem. 2021 Sep 6;16(17):2628-2637. doi: 10.1002/cmdc.202100230. Epub 2021 Jun 9.

Abstract

Nootkatone, an approved insecticide, is a well-known natural product from grapefruit. A series of fused-thiazole derivatives of nootkatone have been synthesized, and these new compounds were tested against several strains of bacteria. Some of these compounds are found to be potent antimicrobial agents against Staphylococcus aureus and Enterococcus faecium with minimum inhibitory concentration (MIC) values as low as 1.56 μg/mL. The lead compound is bactericidal and very potent against S. aureus persisters. These compounds are nontoxic to human cancer cell lines at 10 μm concentration.

Keywords: MRSA; Nootkatone; chimeric compounds; persisters; thiazole.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enterococcus faecium / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Polycyclic Sesquiterpenes / chemistry
  • Polycyclic Sesquiterpenes / pharmacology*
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Polycyclic Sesquiterpenes
  • Thiazoles
  • nootkatone