Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carbolines / chemical synthesis
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Carbolines / chemistry
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Cell Survival / drug effects
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Design
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Fibrinolytic Agents* / chemical synthesis
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Fibrinolytic Agents* / chemistry
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Fibrinolytic Agents* / pharmacology
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Free Radical Scavengers* / chemical synthesis
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Free Radical Scavengers* / chemistry
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Free Radical Scavengers* / pharmacology
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Molecular Structure
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Oligopeptides* / chemical synthesis
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Oligopeptides* / chemistry
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Oligopeptides* / pharmacology
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PC12 Cells
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Phenol / chemistry
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Platelet Aggregation / drug effects*
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Platelet Aggregation Inhibitors* / chemical synthesis
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Platelet Aggregation Inhibitors* / chemistry
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Platelet Aggregation Inhibitors* / pharmacology
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Rats
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Thrombosis / drug therapy
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Thrombosis / prevention & control*
Substances
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Carbolines
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Fibrinolytic Agents
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Free Radical Scavengers
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Oligopeptides
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Platelet Aggregation Inhibitors
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Phenol
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tryptoline
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arginyl-glycyl-aspartic acid