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.