Otro
Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit
Registro en:
Molecules. Basel: Mdpi Ag, v. 19, n. 2, p. 2089-2099, 2014.
1420-3049
10.3390/molecules19022089
WOS:000334418200045
WOS000334418200045.pdf
Autor
Chelucci, Rafael Consolin
Dutra, Luiz Antonio
Lopes Pires, Maria Elisa
Ferreira de Melo, Thais Regina
Bosquesi, Priscila Longhin
Chin, Chung Man
Santos, Jean Leandro dos
Resumen
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. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)