Design, synthesis and cardioprotective effect of a new class of dual-acting agents: Phenolic tetrahydro-β-carboline RGD peptidomimetic conjugates

• Published in: Bioorganic & medicinal chemistry 2007-11, Vol.15 (22), p.6909-6919
• Main Authors: Bi, Wei, Cai, Jianhui, Liu, Sanguang, Baudy-Floc’h, Michèle, Bi, Lanrong
• Format: Article
• Language: English
• Subjects: Animals; Antithrombotic agent; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Carbolines - chemical synthesis; Carbolines - chemistry; Cardiovascular system; Cell Survival - drug effects; Chemical Sciences; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Dual-acting agents; Fibrinolytic Agents - chemical synthesis; Fibrinolytic Agents - chemistry; Fibrinolytic Agents - pharmacology; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Free radicals scavenger; Medical sciences; Miscellaneous; Molecular Structure; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Organic chemistry; PC12 Cells; Pharmacology. Drug treatments; Phenol - chemistry; Phenolic tetrahydro-β-carboline RGD peptidomimetics conjugates; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - chemical synthesis; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Rats; Thrombosis - drug therapy; Thrombosis - prevention & control
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.08.022

In this study, a new class of phenolic tetrahydro-β-carboline RGD peptidomimetic conjugates was designed and synthesized. The radical scavenging activities of these newly synthesized compounds 12a– c were evaluated in PC12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. Compounds 12a– c were efficacious in a rat arterial thrombosis model, and were active in ADP- or PAF-induced in vitro platelet aggregation assays, which suggests these compounds also possess anti-thrombotic activity. The beneficial effects of dual-acting agent 12c were demonstrated on the ischemia-reperfusion induced cardiac infarct size and oxidative change in an in vivo rat model.