Lee Wonhwa, Lee JungIn, Kulkarni Roshan, Kim Mi-Ae, Hwang Jae Sam, Na MinKyun, Bae Jong-Sup
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team Kyungpook National University, Daegu 41566, Republic of Korea.
BK21 Plus KNU Biomedical Convergence Program, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
Sci Rep. 2016 Feb 24;6:21956. doi: 10.1038/srep21956.
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.
本研究的目的是从少棘蜈蚣(SSM)中发现小分子抗凝血剂。从少棘蜈蚣中分离出一种新的酰化多胺(1)和一种新的硫酸化喹啉生物碱(2)。用新生物碱1、2和吲哚乙酸4处理可延长活化部分凝血活酶时间和凝血酶原时间,并抑制凝血酶和活化因子X的活性及生成。此外,化合物1、2和4抑制凝血酶催化的纤维蛋白聚合和血小板聚集。鉴于这些潜在的体外抗血小板活性,化合物1、2和4在体内肺栓塞和动脉血栓形成模型中显示出增强的抗血栓作用。化合物1、2和4在小鼠中也引发了抗凝作用。总的来说,本研究可为将少棘蜈蚣或化合物1、2和4作为预防和治疗疾病的功能性食品成分商业化奠定基础,并为抗凝血剂的开发提供新的支架。