title: Dual anticoagulant/antiplatelet persulfated small molecules.
abstract: A new series of persulfated compounds was synthesized and assayed for in vitro anticoagulant and antiplatelet activities, which may be useful in the treatment of both venous and arterial thrombosis. Persulfation of polyphenolic components of wine, coumarins and other structurally diverse small molecules was achieved with triethylamine-sulphur trioxide adduct. The derivatives were highly effective in increasing the APTT, being trans-resveratrol 3-ß-D-glucopyranoside persulfate (15) the most potent (APTT2=1.5×10(-4) M), and were able to completely block the clotting process at the highest concentration. Compound 15 showed good stability in human plasma and anticoagulation effects in whole blood. trans-Resveratrol 3-ß-D-glucopyranoside persulfate (15) and a series of polysulfated oligoflavonoids (1-4) also exhibited antiplatelet activity by inhibition of arachidonic acid and ADP-induced platelet aggregation.
authors: Centro de Química Medicinal, Universidade do Porto (CEQUIMED-UP), Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, and Serviço de ImunoHemoterapia, Centro de Trombose, Hemostase e Biologia Vascular, Hospital de S. João, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal.
authors: Marta
authors: M
authors: Correia-da-Silva
authors: Emília
authors: E
authors: Sousa
authors: Bárbara
authors: B
authors: Duarte
authors: Franklim
authors: F
authors: Marques
authors: Luís M
authors: LM
authors: Cunha-Ribeiro
authors: Madalena M M
authors: MM
authors: Pinto
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D013463:Sulfuric Acid Esters; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate