Synthesis of antiplatelet ortho-carbonyl hydroquinones with differential action on platelet aggregation stimulated by collagen or TRAP-6

European Journal of Medicinal Chemistry
Diego MéndezEduardo Fuentes

Abstract

Cardiovascular diseases are the leading cause of death in the world. Platelets have a major role in cardiovascular events as they bind to the damaged endothelium activating and forming thrombi. Although some hydroquinone scaffold-containing compounds have known antiplatelet activities, currently there is a lack of evidence on the antiplatelet activity of hydroquinones carrying electron attractor groups. In this work, we evaluate the antiplatelet effect of a series of ortho-carbonyl hydroquinone derivatives on cytotoxicity and function of human platelets, using collagen and thrombin receptor activator peptide 6 (TRAP-6) as agonists. Our structure-activity relationship study shows that gem-diethyl/methyl substitutions and the addition/modifications of the third ring of ortho-carbonyl hydroquinone scaffold influence on the selective index (IC50 TRAP-6/IC50 Collagen) and the inhibitory capacity of platelet aggregation. Compounds 3 and 8 inhibit agonist-induced platelet aggregation in a non-competitive manner with IC50 values of 1.77 ± 2.09 μM (collagen) and 11.88 ± 4.59 μM (TRAP-6), respectively and show no cytotoxicity. Both compounds do not affect intracellular calcium levels and mitochondrial bioenergetics. Consistently, they re...Continue Reading

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Citations

Sep 2, 2020·International Journal of Molecular Sciences·Diego MéndezEduardo Fuentes
May 1, 2021·Antioxidants·Lyanne RodríguezEduardo Fuentes
Sep 1, 2021·Journal of Medicinal Food·Sigrid SanzanaIván Palomo

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