Synthesis and Preliminary Evaluation of N-Oxide Derivatives for the Prevention of Atherothrombotic Events

Author(s)

Rosseto, Leandro Augusto ^[1] ; Lopes Pires, Maria Elisa ^[2] ; Bolognesi Melchior, Aylime Castanho ^[1] ; Bosquesi, Priscila Longhin ^[1] ; Pavan, Aline Renata ^[1] ; Marcondes, Sisi ^[2] ; Chung, Man Chin ^[1] ; dos Santos, Jean Leandro ^[1]

Affiliation

^[1] Univ Estadual Paulista, UNESP, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Estadual Campinas, Dept Farmacol, Fac Ciencias Med, UNICAMP, BR-13083887 Campinas, SP - Brazil

• Document type: Journal article
• Source: Molecules; v. 20, n. 10, p. 18185-18200, OCT 2015.
• Web of Science Citations: 9

Abstract

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. (AU)

• FAPESP's process: 10/02774-5 - Design and synthesis of new acetyl salicilic acid hybrid analogues useful for treatment and prevention of atherothrombosis
• Grantee: Leandro Augusto Rosseto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation