Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

Autor(es)

Chelucci, Rafael Consolin ^[1] ; Dutra, Luiz Antonio ^[1] ; Lopes Pires, Maria Elisa ^[1] ; Ferreira de Melo, Thais Regina ^[1] ; Bosquesi, Priscila Longhin ^[1] ; Chung, Man Chin ^[1] ; dos Santos, Jean Leandro ^[1]

Afiliação do(s) autor(es)

^[1] UNESP, Fac Ciencias Farmaceut, Dept Farmacos & Med, BR-14801902 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 19, n. 2, p. 2089-2099, FEB 2014.
• Citações Web of Science: 16

Resumo

Nonsteroidal anti-inflammatory drugs (NSAIDs) 1-5 containing an N-acyl hydrazone subunit were prepared and their antiplatelet and antithrombotic activities assessed in vitro and in vivo. Compounds 1-5 inhibited the platelet aggregation induced by adenosine diphosphate and/or arachidonic acid, with inhibition rates of 18.0%-61.1% and 65.9%-87.3%, respectively. Compounds 1 and 5 were the most active compounds, inhibiting adenosine-diphosphate-induced platelet aggregation by 57.2% and 61.1%, respectively. The inhibitory rates for arachidonic-acid-induced platelet aggregation were similar for compound 2 (80.8%) and acetylsalicylic acid (ASA, 80%). After their oral administration to mice, compounds 1, 3, and 5 showed shorter mean bleeding times than ASA. Compounds 1 and 5 also protected against thromboembolic events, with survival rates of 40% and 33%, respectively, compared with 30% for ASA. In conclusion, these results indicate that these novel NSAIDs containing an NAH subunit may offer better antiplatelet and antithrombotic activities than ASA. (AU)

• Processo FAPESP: 12/50359-2 - Planejamento, síntese e avaliação farmacológica de novas moléculas híbridas úteis ao tratamento de desordens hematológicas
• Beneficiário: Jean Leandro dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE
• Processo FAPESP: 11/15204-5 - Síntese e Avaliação Farmacológica de novos compostos híbridos úteis para tratamento dos sintomas de anemia falciforme
• Beneficiário: Thaís Regina Ferreira de Melo
• Modalidade de apoio: Bolsas no Brasil - Mestrado