Sponge-Derived 24-Homoscalaranes as Potent Anti-Inflammatory Agents

Mar Drugs. 2020 Aug 19;18(9):434. doi: 10.3390/md18090434.

Abstract

Scalarane-type sesterterpenoids are known for their therapeutic potential in cancer treatments. However, the anti-inflammatory properties of this class of metabolites remain elusive. Our current work aimed to investigate the anti-inflammatory scalaranes from marine sponge Lendenfeldia sp., resulting in the isolation of six new 24-homoscalaranes, lendenfeldaranes E-J (1-6). The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of 1 was established by electronic circular dichroism (ECD) calculations. Compounds 2 and 3 were discovered to individually reduce the generation of superoxide anions, and compound 1 displayed an inhibitor effect on the release of elastase. These three compounds were proven to be the first anti-neutrophilic scalaranes.

Keywords: 24-homoscalarane; Lendenfeldia; NADPH oxidase; anti-neutrophilic inflammation; elastase release; lendenfeldarane; sesterterpenoid; superoxide anion.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Humans
  • Leukocyte Elastase / metabolism
  • Molecular Structure
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Porifera / chemistry*
  • Secretory Pathway
  • Sesterterpenes / chemistry
  • Sesterterpenes / isolation & purification
  • Sesterterpenes / pharmacology*
  • Structure-Activity Relationship
  • Superoxides / metabolism

Substances

  • Anti-Inflammatory Agents
  • Sesterterpenes
  • Superoxides
  • ELANE protein, human
  • Leukocyte Elastase