title: Synthesis, antiplatelet and antithrombotic activities of resveratrol derivatives with NO-donor properties.
abstract: 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.
authors.affiliation: São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil. Electronic address: luizdutra_qf@yahoo.com.br.
authors.forename: Luiz Antonio
authors.initials: LA
authors.lastname: Dutra
authors.affiliation: University of Campinas (Unicamp), Faculty of Medical Science, Campinas, SP, Brazil.
authors.forename: Jéssica Frade O
authors.initials: JFO
authors.lastname: Guanaes
authors.affiliation: São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil.
authors.forename: Nadine
authors.initials: N
authors.lastname: Johmann
authors.affiliation: University of Campinas (Unicamp), Faculty of Medical Science, Campinas, SP, Brazil.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Lopes Pires
authors.affiliation: São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil.
authors.forename: Chung Man
authors.initials: CM
authors.lastname: Chin
authors.affiliation: University of Campinas (Unicamp), Faculty of Medical Science, Campinas, SP, Brazil.
authors.forename: Sisi
authors.initials: S
authors.lastname: Marcondes
authors.affiliation: São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil. Electronic address: santosjl@fcfar.unesp.br.
authors.forename: Jean Leandro
authors.initials: JL
authors.lastname: Dos Santos
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001760:Bleeding Time; D003094:Collagen / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D051379:Mice; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000494:pharmacology*; D009573:Nitrites / Q000032:analysis; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D005343:Fibrinolytic Agents; D006835:Hydrazones; D020030:Nitric Oxide Donors; D009573:Nitrites; D010069:Oxadiazoles; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D007548:Isosorbide Dinitrate; D001241:Aspirin
keywords: Antithrombotic activity; Furoxan; Molecular modification; Platelet aggregation inhibition; Resveratrol