Potent inhibition of bacterial neuraminidase activity by pterocarpans isolated from the roots of Lespedeza bicolor

Bioorg Med Chem Lett. 2011 Oct 15;21(20):6100-3. doi: 10.1016/j.bmcl.2011.08.046. Epub 2011 Aug 24.

Abstract

Bacterial neuraminidase has been highlighted as a key enzyme for pathogenic infection and sepsis. Six pterocarpans displaying significant levels of neuraminidase inhibitory activity were isolated from the root bark of Lespedeza bicolor. The isolated compounds were identified as three new pterocarpans (1-3) together with known compounds erythrabyssin II (4), lespebuergine G4 (5), and 1-methoxyerythrabyssin II (6). The new compounds were characterized as bicolosin A (1), bicolosin B (2), and bicolosin C (3). All compounds inhibited bacterial neuraminidase in a dose-dependent manner with significant inhibition (IC(50)=0.09-3.25 μM). All neuraminidase inhibitors screened were found to exhibit noncompetitive kinetics. The three most potent neuraminidase inhibitors (1, 3 and 6) feature a methoxy substitution on C-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / pharmacology*
  • Clostridium perfringens / drug effects
  • Clostridium perfringens / enzymology*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Gas Gangrene / drug therapy
  • Gas Gangrene / enzymology
  • Humans
  • Lespedeza / chemistry*
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Plant Roots / chemistry
  • Pterocarpans / isolation & purification*
  • Pterocarpans / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Pterocarpans
  • Neuraminidase