Polysulfated Xanthones: Multipathway Development of a New Generation of Dual Anticoagulant/Antiplatelet 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: 5373-5384

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Proceedings

ISI Web of Knowledge - 43 Citations

Scopus - 46 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-NRY

DOI: 10.1021/jm2006589

Abstract (EN): A multipathway strategy was used to evaluate the in vitro and in vivo antithrombotic effects of a new synthetic family of sulfated small molecules. Polysulfated xanthonosides showed highly effective anticoagulation effects in vitro, both in plasma (dotting times) and in whole human blood (thromboelastography), as well as in vivo (ip administration, mice). Physicochemical properties were assessed for mangiferin heptasulfate (7), which showed high solubility and stability in water and in human plasma and no putative hepatotoxicity in vivo. Mangiferin heptasulfate (7) was found to be a direct inhibitor of FXa, while persulfated 3,6-(O-beta-glucopyranosyl)xanthone (13) acted as a dual inhibitor of FXa (directly and by antithrombin III activation). By impedance aggregometry, compounds 7 and 13 exhibited the antiplatelet effect by inhibition of both arachidonic acid and ADP-induced platelet aggregation. Dual anticoagulant/antiplatelet agents, such as sulfated xanthonosides 7 and 13, are expected to lead to a new therapeutic approach for the treatment of both venous and arterial thrombosis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12