SMALL MOLECULE ANTICOAGULANTS DERIVED FROM SCOLOPENDRA SUBSPINIPES MUTILANS

JungIn Lee, Jong-Sup Bae and MinKyun Na

Pharmacy Department, Chungnam National University, Daejeon, South Korea

Abstract

The centipede Scolopendra subspinipes mutilans L. Koch (SSM) is a medicinal resource listed in the Korean Herbal Pharmacopeia and Chinese Pharmacopeia which has been applied to treat stroke and stroke-related hemiplegia, epileptic seizures, tetanus, and pain. Our study has aimed to discover small molecule anticoagulants from the whole material of SSM that has been clinically used. In this study, we have isolated a new acylated polyamine (1) and a new sulfated quinoline alkaloid (2), together with 6 small molecule alkaloids, and examined the anticoagulant activity of isolated compounds. Treatment with new alkaloids (1 and 2) and indole acetic acid 4 prolonged the prothrombin time (PT), activated partial thromboplastin time (aPTT) and inhibited the production of activated factor X (FXa) and thrombin. Compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Furthermore, compounds 1, 2, and 4 showed enhanced anti-thrombotic effects in vivo pulmonary embolism and arterial thrombosis model. Our findings may serve the groundwork for compounds 1, 2, and 4 as new scaffolds for the development of anticoagulants or commercializing the insect material as functional food component.

Keywords: Scolopendra subspinipes mutilans, new alkaloids, anticoagulants.