Dual-acting agents that possess free radical scavenging and antithrombotic activities: design, synthesis, and evaluation of phenolic tetrahydro-beta-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 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.
Bi
Wei
W
Second Affiliated Hospital of HeBei Medical University, Shijiazhuang, PR China. tok2@llnl.gov
Bi
Lanrong
L
Cai
Jianhui
J
Liu
Sanguang
S
Peng
Shiqi
S
Fischer
Nicholas O
NO
Tok
Jeffrey B-H
JB
Wang
Guohua
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002243:Carbolines / Q000737:chemistry*; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006859:Hydrogen / Q000737:chemistry; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D016716:PC12 Cells; D019800:Phenol / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013927:Thrombosis
D002243:Carbolines; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D009842:Oligopeptides; D010972:Platelet Activating Factor; D019800:Phenol; D000244:Adenosine Diphosphate; C047981:arginyl-glycyl-aspartic acid; D006859:Hydrogen