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

A new approach to construct a single dual-acting agent is described. Compounds 6a–c are potent free radical scavengers as demonstrated by the EC50 values in PC12 cell survival assay in term of NO, H2O2, 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.

Graphical abstractWe describe the design and synthesis of dual-acting agents having both free radical scavenging and antithrombolic activities. These compounds may potentially be beneficial in treating myocardial ischemic/reperfusion injuries.Figure optionsDownload full-size imageDownload as PowerPoint slide