Design, synthesis and cardioprotective effect of a new class of dual-acting agents: phenolic tetrahydro-beta-carboline RGD peptidomimetic conjugates.
In this study, a new class of phenolic tetrahydro-beta-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.
Bi
Wei
W
Second Hospital of HeBei Medical University, Shijiazhuang 050000, PR China.
Cai
Jianhui
J
Liu
Sanguang
S
Baudy-Floc'h
Michèle
M
Bi
Lanrong
L
D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D019800:Phenol / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*