Synthesis and preliminary evaluation of N-oxide derivatives for the prevention of atherothrombotic events
Carregando...
Arquivos
Data
2015
Autores
Rosseto, Leandro Augusto [UNESP]
Pires, Maria Elisa Lopes
Melchior, Aylime Castanho Bolognesi [UNESP]
Bosquesi, Priscila Longhin [UNESP]
Pavan, Aline Renata [UNESP]
Marcondes, Sisi
Chin, Chung Man [UNESP]
Santos, Jean Leandro dos [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Molecules
Resumo
Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs. A series of N-oxide derivatives (furoxan and benzofuroxan) were synthesized and characterized as potential antiplatelet/antithrombotic compounds. All compounds (3a,b, 4a,b, 8a,b, 9a,b, 13a,b and 14a,b) inhibited platelet aggregation induced by adenosine-5-diphosphate, collagen, and arachidonic acid. All compounds protected mice from pulmonary thromboembolism induced by a mixture of collagen and epinephrine; however, benzofuroxan derivatives (13a,b and 14a,b) were the most active compounds, reducing thromboembolic events by up to 80%. N-oxide derivative 14a did not induce genotoxicity in vivo. In conclusion, 14a has emerged as a new antiplatelet/antithrombotic prototype useful for the prevention of atherothrombotic events.
Descrição
Palavras-chave
N-oxide, Antiplatelet activity, Atherothrombosis, Benzofuroxan, Bleeding time, Furoxan, Genotoxicity
Como citar
Molecules (basel, Switzerland), v. 20, n. 10, p. 18185-18200, 2015.