Butyrolactone and sesquiterpene derivatives as inhibitors of iNOS from the roots of Lindera glauca

Bioorg Chem. 2021 Jun:111:104871. doi: 10.1016/j.bioorg.2021.104871. Epub 2021 Mar 29.

Abstract

Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J - L (5-7), linderaguaianols A and B (8 and 9), together with six known ones 10-15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo2(AcO)4-induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1-4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC50 value of 1.73 ± 0.18 μM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses.

Keywords: Anti-inflammatory activity; Butyrolactone; Lindera glauca; Sesquiterpene; iNOS inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Lindera / chemistry*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Mice
  • Molecular Structure
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Roots / chemistry*
  • RAW 264.7 Cells
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Sesquiterpenes
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse