Anti-inflammatory alkaloids from the stems of Picrasma quassioides BENNET

Chem Pharm Bull (Tokyo). 2011;59(3):359-64. doi: 10.1248/cpb.59.359.

Abstract

During further chemical and biological investigations of Picrasma quassioides BENNET, four new bis-β-carboline alkaloids, quassidines E-H (1-4), and three new β-carboline alkaloids, canthin-16-one-14-butyric acid (5), 3-(1,1-dimethoxylmethyl)-β-carboline (6), and 6,12-dimethoxy-3-formyl-β-carboline (7), were isolated from its anti-inflammatory CHCl(3)-soluble fraction. Structures of new compounds were elucidated and characterized by MS and NMR analysis. A plausible biogenetic pathway for quassidine E (1), the first bis-β-carboline alkaloid in which a canthin-6-one moiety and a β-carboline moiety were connected together by a single carbon-carbon bond from the nature, was proposed. Quassidines E-G (1-3) showed potent inhibitory activity on the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), or interleukin 6 (IL-6) in mouse monocyte-macrophage RAW264.7 cells stimulated by lipopolysaccharide (LPS). Analysis of anti-inflammatory activity of all β-carboline and bis-β-carboline alkaloids from P. quassioides showed that the carbonyl groups or double carbon-carbon bonds at C-14 for β-carbolines and C-14' for bis-β-carbolines were bioactive groups for their in vitro anti-inflammatory activity. Structure-activity relationship of these compounds on inhibitory activity of the three inflammatory cytokines was discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology
  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line, Tumor
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / toxicity
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Conformation
  • Nitric Oxide / metabolism
  • Picrasma / chemistry*
  • Plant Stems / chemistry
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide