Abstract
The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Alkaloids / isolation & purification
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Alkaloids / pharmacology*
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Animals
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Anticoagulants / isolation & purification
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Anticoagulants / pharmacology*
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Disease Models, Animal
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Diterpene Alkaloids
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Drug Discovery
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Drugs, Chinese Herbal / chemistry*
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Factor Xa / biosynthesis
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Fibrin / antagonists & inhibitors
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Fibrin / metabolism
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Fibrinolytic Agents / isolation & purification
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Fibrinolytic Agents / pharmacology*
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Indoleacetic Acids / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Partial Thromboplastin Time
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Platelet Aggregation / drug effects
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Polyamines / isolation & purification
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Polyamines / pharmacology*
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Polymerization
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Prothrombin Time
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Pulmonary Embolism / blood
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Pulmonary Embolism / drug therapy*
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Pulmonary Embolism / pathology
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Quinolines / isolation & purification
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Quinolines / pharmacology
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Thrombin / antagonists & inhibitors
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Thrombin / biosynthesis
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Thrombosis / blood
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Thrombosis / drug therapy*
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Thrombosis / pathology
Substances
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Alkaloids
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Anticoagulants
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Diterpene Alkaloids
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Drugs, Chinese Herbal
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Fibrinolytic Agents
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Indoleacetic Acids
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Polyamines
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Quinolines
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indoleacetic acid
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Fibrin
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Thrombin
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Factor Xa
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scolopendra alkaloids