Dual anticoagulant/antiplatelet persulfated small molecules

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Biochemistry

Background:

• Thrombosis, encompassing both venous and arterial types, remains a significant clinical challenge.
• Developing novel therapeutic agents with anticoagulant and antiplatelet properties is crucial for effective treatment.
• Polyphenolic compounds and their derivatives are explored for diverse biological activities.

Purpose of the Study:

• To synthesize and evaluate novel persulfated compounds for their in vitro anticoagulant and antiplatelet activities.
• To identify potent derivatives for potential application in managing thrombotic disorders.
• To assess the stability and efficacy of lead compounds in relevant biological matrices.

Main Methods:

• Synthesis of persulfated compounds via reaction with triethylamine-sulphur trioxide adduct.
• Assay of anticoagulant activity by measuring activated partial thromboplastin time (APTT).
• Evaluation of antiplatelet activity through inhibition of arachidonic acid and ADP-induced platelet aggregation.

Main Results:

• A series of persulfated compounds were successfully synthesized.
• Trans-resveratrol 3-ß-D-glucopyranoside persulfate (15) demonstrated potent anticoagulant activity, significantly increasing APTT.
• Compounds 15 and polysulfated oligoflavonoids (1-4) exhibited significant antiplatelet effects.
• Compound 15 displayed good stability in human plasma and anticoagulation effects in whole blood.

Conclusions:

• Persulfated derivatives of polyphenols, coumarins, and other small molecules possess significant in vitro anticoagulant and antiplatelet properties.
• Trans-resveratrol 3-ß-D-glucopyranoside persulfate (15) is a highly potent candidate for further investigation in thrombosis treatment.
• These findings suggest a promising new class of compounds for managing venous and arterial thrombosis.