Synthesis, antiplatelet and antithrombotic activities of resveratrol derivatives with NO-donor properties

Autor(es)

Dutra, Luiz Antonio ; Guanaes, Jessica Frade O. ; Johmann, Nadine ; Lopes Pires, Maria Elisa ; Chin, Chung Man ; Marcondes, Sisi ; Dos Santos, Jean Leandro

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry Letters; v. 27, n. 11, p. 2450-2453, JUN 1 2017.
• Citações Web of Science: 11

Resumo

Resveratrol (RVT) is a stilbene with a protective effect on the cardiovascular system; however, drawbacks including low bioavailability and fast metabolism limit its efficacy. In this work we described new resveratrol derivatives with nitric oxide (NO) release properties, ability to inhibit platelet aggregation and in vivo antithrombotic effect. Compounds (4a-f) were able to release NO in vitro, at levels ranging from 24.1% to 27.4%. All compounds (2a-f and 4a-f) have exhibited platelet aggregation inhibition using as agonists ADP, collagen and arachidonic acid. The most active compound (4f) showed reduced bleeding time compared to acetylsalicylic acid (ASA) and protected up to 80% against in vivo thromboembolic events. These findings suggest that hybrid resveratrol-furoxan (4f) is a novel lead compound able to prevent platelet aggregation and thromboembolic events. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 15/19531-1 - Inibição de histona deacetilase (HDAC-1 e HDAC-2) como alvos para indução de hemoglobina fetal na anemia falciforme
• Beneficiário: Jean Leandro dos Santos
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/21271-8 - Avaliação farmacológica de derivados de resveratrol como inibidores duplos de Bromodomain/PPAR para o tratamento da dislipidemia
• Beneficiário: Luiz Antonio Dutra
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 14/03945-9 - Planejamento, síntese e avaliação farmacológica de novos compostos derivados de resveratrol úteis ao tratamento da dislipidemia
• Beneficiário: Luiz Antonio Dutra
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/15520-4 - Planejamento, síntese, e avaliação farmacológica de novos compostos 1,2,5-oxadiazol-2-óxido úteis como preventivos de aterotrombose
• Beneficiário: Luiz Antonio Dutra
• Linha de fomento: Bolsas no Brasil - Mestrado