Drimane sesquiterpene esters produced by Aspergillus insuetus BF-1613 as inhibitors of sterol O-acyltransferase

J Antibiot (Tokyo). 2024 Dec;77(12):837-841. doi: 10.1038/s41429-024-00774-8. Epub 2024 Oct 10.

Abstract

A new drimane sesquiterpene ester, designated insuetusolate (1), and four reported ones (2-5) were isolated from a culture broth of Aspergillus insuetus BF-1613. The chemical structure of 1 was elucidated by extensive spectroscopic analyses, including MS and NMR. Compound 1 has a drimane-type sesquiterpene core with a 2'E,4'E,6'E-octatrienoate side chain. All these drimane sesquiterpene esters inhibited both sterol O-acyl transferase 1 (SOAT1) and 2 (SOAT2), but exhibited slightly potent inhibition against SOAT1 than SOAT2 with selectivity index (SI) [log (IC50 for SOAT1/ IC50 for SOAT2)] values ranging from -0.24 to -0.94.

MeSH terms

  • Aspergillus*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Esters* / chemistry
  • Esters* / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Polycyclic Sesquiterpenes* / chemistry
  • Polycyclic Sesquiterpenes* / isolation & purification
  • Polycyclic Sesquiterpenes* / pharmacology
  • Sesquiterpenes* / chemistry
  • Sesquiterpenes* / isolation & purification
  • Sesquiterpenes* / pharmacology
  • Sterol O-Acyltransferase 2
  • Sterol O-Acyltransferase* / antagonists & inhibitors

Substances

  • Sterol O-Acyltransferase
  • Sesquiterpenes
  • drimane
  • Polycyclic Sesquiterpenes
  • Esters
  • sterol O-acyltransferase 1
  • Enzyme Inhibitors
  • Sterol O-Acyltransferase 2