Phenolic bisabolane and cuparene sesquiterpenoids with anti-inflammatory activities from the deep-sea-derived Aspergillus sydowii MCCC 3A00324 fungus

Bioorg Chem. 2020 Dec;105:104420. doi: 10.1016/j.bioorg.2020.104420. Epub 2020 Oct 22.

Abstract

Seventeen undescribed sesquiterpenoids including 14 phenolic bisabolanes, namely asperbisabolanes A-N (1-14), and 3 cuparenes (aspercuparenes A-C, 15-17), together with 10 known bisabolane analogues (18-27) were isolated from the EtOAc extract of fermented cultures of the deep sea sediment-derived fungus Aspergillus sydowii MCCC 3A00324. The new structures were established on the basis of extensive NMR and HRESIMS spectroscopic data analyses, while their absolute configurations were assigned by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra or reported data in literature. Asperbisabolanes A (1) and B (2) are the first examples of bisabolane sesquiterpenoids featuring a 6/6/6 tricyclic nucleus. Compound 3 possessed a novel seco-bisabolane skeleton with a rare dioxolane ring moiety, while asperbisabolane K (11) represents the first case of bisabolanes bearing a rare methylsulfonyl group. All the isolated compounds (1-27) were evaluated their activities against NO secretion in LPS-activated BV-2 microglia cells. As a result, 6, 12, 16, and 25-27 exhibited the inhibition rate over 45% at a concentration of 10 µM. Moreover, 12 exerted the anti-inflammatory activity by inhibiting the NF-κB-activated pathway in dose-dependent manner.

Keywords: Anti-inflammatory activities; Aspergillus sydowii; Bisabolanes; Deep-sea-derived fungus; Sesquiterpenoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspergillus / chemistry*
  • Aspergillus / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fermentation
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Mice
  • Molecular Structure
  • Monocyclic Sesquiterpenes / chemistry
  • Monocyclic Sesquiterpenes / isolation & purification
  • Monocyclic Sesquiterpenes / pharmacology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Monocyclic Sesquiterpenes
  • NF-kappa B
  • Sesquiterpenes
  • cuparene
  • Nitric Oxide

Supplementary concepts

  • Aspergillus sydowii