A new class of β-carboline alkaloid-peptide conjugates with therapeutic efficacy in acute limb ischemia/reperfusion injury

Eur J Med Chem. 2011 May;46(5):1453-62. doi: 10.1016/j.ejmech.2011.01.021. Epub 2011 Jan 21.

Abstract

We describe a novel class of β-carboline alkaloid-peptide conjugates that possess both free radical scavenging and thrombolytic activity. These conjugates demonstrate therapeutic efficacy in a rat arterial thrombosis assay, as well as free radical scavenging capacity as evaluated in a PC12 cell survival assay. Our results indicate that β-carboline alkaloid-peptide conjugate 26a exerts a significant protective effect against local and remote organ injury induced by limb I/R injury in the rat.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Disease
  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Animals
  • Carbolines / chemical synthesis
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Cell Survival / drug effects
  • Extremities / blood supply*
  • Extremities / pathology
  • Free Radical Scavengers / metabolism
  • Ischemia / drug therapy*
  • Ischemia / pathology
  • Molecular Dynamics Simulation
  • Molecular Structure
  • PC12 Cells
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Rats
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Carbolines
  • Free Radical Scavengers
  • Peptides