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


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Apr 2020
Historique:
received: 05 12 2019
revised: 23 02 2020
accepted: 24 02 2020
pubmed: 11 3 2020
medline: 1 12 2020
entrez: 11 3 2020
Statut: ppublish

Résumé

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 (IC

Identifiants

pubmed: 32155530
pii: S0223-5234(20)30154-9
doi: 10.1016/j.ejmech.2020.112187
pii:
doi:

Substances chimiques

Hydroquinones 0
Peptide Fragments 0
Platelet Aggregation Inhibitors 0
thrombin receptor peptide (42-47) 0
Collagen 9007-34-5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

112187

Informations de copyright

Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Diego Méndez (D)

Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca, Chile.

Félix A Urra (FA)

Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; Network for Snake Venom Research and Drug Discovery, Santiago, Chile. Electronic address: felixurraf@u.uchile.cl.

Juan Pablo Millas-Vargas (JP)

Instituto de Química de Recursos Naturales, Programa de Investigación Asociativa en Cáncer Gástrico (PIA-CG), Universidad de Talca, Talca, Chile.

Marcelo Alarcón (M)

Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca, Chile.

Julio Rodríguez-Lavado (J)

Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

Iván Palomo (I)

Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca, Chile.

Andrés Trostchansky (A)

Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.

Ramiro Araya-Maturana (R)

Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca, Chile; Instituto de Química de Recursos Naturales, Programa de Investigación Asociativa en Cáncer Gástrico (PIA-CG), Universidad de Talca, Talca, Chile; Network for Snake Venom Research and Drug Discovery, Santiago, Chile. Electronic address: raraya@utalca.cl.

Eduardo Fuentes (E)

Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca, Chile. Electronic address: edfuentes@utalca.cl.

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Classifications MeSH