Synthesis and characterization of novel indole derivatives reveal improved therapeutic agents for treatment of ischemia/reperfusion (I/R) injury

J Med Chem. 2010 Sep 23;53(18):6763-7. doi: 10.1021/jm100529e.

Abstract

To develop more potent therapeutic agents with therapeutic efficacy for ischemia/reperfusion (I/R) injury, we linked an antiinflammatory moiety (1,3-dioxane derivative) to the key pharmacophoric moiety of melatonin. We hypothesized that the resulting new indole derivatives might induce a synergistic protection against oxidative damage associated with I/R injury. Our results indicate that one of these indole derivatives (7) manifests potent antiinflammatory antioxidant effects and exerts a protective effect against skeletal muscle injury and associated lung injury following limb I/R in rats.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Capillary Permeability
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Hindlimb / blood supply
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Inflammation / drug therapy
  • Lipid Peroxidation / drug effects
  • Lung Injury / drug therapy
  • Lung Injury / metabolism
  • Lung Injury / pathology
  • Mice
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology
  • PC12 Cells
  • Rats
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Free Radical Scavengers
  • Indoles