Flavonoids with an Oligopolysulfated Moiety A New Class of Anticoagulant Agents

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Marta Correia da Silva (Author) Other; Emilia Sousa (Author) FFUP; Barbara Duarte (Author) Other; Franklim Marques (Author) FFUP; Felix Carvalho (Author) FFUP; Luis M Cunha Ribeiro (Author) Other; Madalena M M Pinto (Author) FFUP

Journal

Title: Journal of Medicinal Chemistry

Vol. 54 No. 1

Pages: 95-106

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Proceedings

ISI Web of Knowledge - 48 Citations

Scopus - 51 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-VVM

DOI: 10.1021/jm1013117

Abstract (EN): 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 activity 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

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12