title: Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans.
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.
authors.affiliation: 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.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: JungIn
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Roshan
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: Department of Agricultural Biology, The National Academy of Agricultural Science, RDA, 166 Nongsaengmyoungro, Wanju-gun, 55365, Republic of Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biology, The National Academy of Agricultural Science, RDA, 166 Nongsaengmyoungro, Wanju-gun, 55365, Republic of Korea.
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.affiliation: 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.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000215:Acylation; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D000077743:Diterpene Alkaloids; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D015951:Factor Xa / Q000096:biosynthesis; D005337:Fibrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007210:Indoleacetic Acids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D011073:Polyamines / Q000302:isolation & purification / Q000494:pharmacology*; D058105:Polymerization; D011517:Prothrombin Time; D011655:Pulmonary Embolism / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011804:Quinolines / Q000302:isolation & purification / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000470:Alkaloids; D000925:Anticoagulants; D000077743:Diterpene Alkaloids; D004365:Drugs, Chinese Herbal; D005343:Fibrinolytic Agents; D007210:Indoleacetic Acids; D011073:Polyamines; D011804:Quinolines; C030737:indoleacetic acid; D005337:Fibrin; D013917:Thrombin; D015951:Factor Xa; C574917:scolopendra alkaloids