Flavonoids with an Oligopolysulfated Moiety: A New Class of Anticoagulant Agents

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• 作者：Marta Correia-da-Silva ; Em铆lia Sousa ; B谩rbara Duarte ; Franklim Marques ; F茅lix Carvalho ; Lu铆s M. Cunha-Ribeiro ; Madalena M. M. Pinto
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 13, 2011
• 年：2011
• 卷：54
• 期：1
• 页码：95-106
• 全文大小：1059K
• 年卷期：v.54,no.1(January 13, 2011)
• ISSN：1520-4804

文摘

Polysulfated (oligo)flavonoids were synthesized and assayed for their in vitro and in vivo anticoagulant activities. The approach was based on molecular hybridization of two classes of anticoagulants, sulfated polysaccharides and sulfated flavonoids. The synthesis was optimized using microwave-assisted sulfation with triethylamine-sulfur trioxide. The obtained polysulfated flavonosides were highly effective in increasing clotting times and able to completely block the clotting process, in contrast to their corresponding aglycones. The thromboelastography proved that polysulfated flavonosides possess good whole blood anticoagulation activity. The following structure鈭抋ctivity relationships were found: 3-O-rutinosides (10, 13) were direct inhibitors of FXa, while 7-O-rutinosides (7, 8) showed inhibition of FXa by ATIII activation. Furthermore, compounds 7 and 13 were stable in plasma and active in vivo and preliminary toxicity studies would lead us to rule out acute side effects. From the overall results, the polysulfated flavonosides showed the potential as new effective and safe agents for anticoagulant therapy.