Dual-acting agents that possess free radical scavenging and antithrombotic activities: design, synthesis, and evaluation of phenolic tetrahydro-beta-carboline RGD peptide conjugates

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4523-7. doi: 10.1016/j.bmcl.2006.06.024. Epub 2006 Jun 23.

Abstract

A new approach to construct a single dual-acting agent is described. Compounds 6a-c are potent free radical scavengers as demonstrated by the EC(50) values in PC12 cell survival assay in term of NO, H(2)O(2), and ()OH scavenging activity. The Ach-induced vaso-relaxation assay further confirms the potent NO scavenging activity of compounds 6a-c. In addition, 6a-c are efficacious in a rat arterial thrombosis, and are active in ADP- or PAF-induced in vitro platelet aggregation assay, suggesting that compounds 6a-c also possess anti-thrombotic activities. Since both free radical and thrombogenesis are important risk factors in myocardial ischemic/reperfusion injuries, these dual-acting agents having both free radical scavenging and antithrombolic activities may potentially be beneficial toward their treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Animals
  • Carbolines / chemistry*
  • Drug Design*
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology
  • Free Radical Scavengers / chemical synthesis*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Hydrogen / chemistry
  • Molecular Structure
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • PC12 Cells
  • Phenol / chemistry*
  • Platelet Activating Factor / pharmacology
  • Platelet Aggregation / drug effects
  • Rabbits
  • Rats
  • Thrombosis

Substances

  • Carbolines
  • Fibrinolytic Agents
  • Free Radical Scavengers
  • Oligopeptides
  • Platelet Activating Factor
  • Phenol
  • Adenosine Diphosphate
  • arginyl-glycyl-aspartic acid
  • Hydrogen