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

Molecules

Rafael Consolin Chelucci¹  Luiz Antônio Dutra¹  Maria Elisa Lopes Pires¹  Thais Regina Ferreira de Melo¹  Priscila Longhin Bosquesi¹  Man Chin Chung¹ 

[1] Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas–UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil;

关键词: hydrazone;    antiplatelet;    antithrombotic;    NSAIDs;    bleeding time;   

DOI  :  10.3390/molecules19022089

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.