期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 114, 期 -, 页码 33-40出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.02.063
关键词
Propylene glycol alginate sodium sulfate; Antithrombotic; Anticoagulant; Oxidative reduction; Molecular weight
资金
- Shandong Science and Technology Project [2014GGH215001]
- Qingdao Independent Innovation Project [15-4-13-zdzx-hy]
- Special Fund for Marine Scientific Research in the Public Interest [201405038]
Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for nearly 30 years. To extend the applications of PSS, a series of low-molecular-weight PSSs (named FPs) were prepared by oxidative-reductive depolymerization, and the antithrombotic activities were investigated thoroughly in vitro and in vivo. The bioactivity evaluation demonstrated a positive correlation between the molecular weight and the anticoagulant and antithrombotic activities of FPs. FPs could prolong the APTT and clotting time and reduce platelet aggregation significantly. FPs could also effectively inhibit factor IIa in the presence of AT-III and HC-II. FPs decreased the wet weights and lengths of the thrombus and increased occlusion times in vivo. FP-6k, a PSS fragment with a molecular weight of 6 kDa, is an optimal antithrombotic candidate for further study and showed little chance for hemorrhagic action. (C) 2016 Elsevier Masson SAS. All rights reserved.
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