Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans

Sci Rep. 2016 Feb 24;6:21956. doi: 10.1038/srep21956.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Animals
  • Anticoagulants / isolation & purification
  • Anticoagulants / pharmacology*
  • Disease Models, Animal
  • Diterpene Alkaloids
  • Drug Discovery
  • Drugs, Chinese Herbal / chemistry*
  • Factor Xa / biosynthesis
  • Fibrin / antagonists & inhibitors
  • Fibrin / metabolism
  • Fibrinolytic Agents / isolation & purification
  • Fibrinolytic Agents / pharmacology*
  • Indoleacetic Acids / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Partial Thromboplastin Time
  • Platelet Aggregation / drug effects
  • Polyamines / isolation & purification
  • Polyamines / pharmacology*
  • Polymerization
  • Prothrombin Time
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / pathology
  • Quinolines / isolation & purification
  • Quinolines / pharmacology
  • Thrombin / antagonists & inhibitors
  • Thrombin / biosynthesis
  • Thrombosis / blood
  • Thrombosis / drug therapy*
  • Thrombosis / pathology

Substances

  • Alkaloids
  • Anticoagulants
  • Diterpene Alkaloids
  • Drugs, Chinese Herbal
  • Fibrinolytic Agents
  • Indoleacetic Acids
  • Polyamines
  • Quinolines
  • indoleacetic acid
  • Fibrin
  • Thrombin
  • Factor Xa
  • scolopendra alkaloids