Ganoderma cochlear Metabolites as Probes to Identify a COX-2 Active Site and as in Vitro and in Vivo Anti-Inflammatory Agents

Org Lett. 2020 Apr 3;22(7):2574-2578. doi: 10.1021/acs.orglett.0c00452. Epub 2020 Mar 13.

Abstract

(±)-Dispirocochlearoids A-C (1-3), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from Ganoderma cochlear. 1-3 are selective COX-2 inhibitors with an IC50 value of (-)-2 at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site. In vivo anti-inflammatory activities of (-)-2 were performed against acute lung injury in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Catalytic Domain
  • Cyclooxygenase 2 / analysis*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Ganoderma / chemistry*
  • Ganoderma / metabolism
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Molecular Conformation
  • Molecular Probes / chemistry
  • Molecular Probes / metabolism
  • Molecular Probes / pharmacology*
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Lipopolysaccharides
  • Molecular Probes
  • Cyclooxygenase 2