title: Antiplatelet and antithrombotic activities of non-steroidal anti-inflammatory drugs containing an N-acyl hydrazone subunit.
abstract: 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.
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. rafaelchelucci@hotmail.com.
authors.forename: Rafael Consolin
authors.initials: RC
authors.lastname: Chelucci
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. luizdutra_qf@yahoo.com.br.
authors.forename: Luiz Antônio
authors.initials: LA
authors.lastname: Dutra
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. mariaelisalopes@yahoo.com.br.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Lopes Pires
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. trfmelo@gmail.com.
authors.forename: Thais Regina Ferreira
authors.initials: TR
authors.lastname: de Melo
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. bosquesi@fcfar.unesp.br.
authors.forename: Priscila Longhin
authors.initials: PL
authors.lastname: Bosquesi
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. chungmc@fcfar.unesp.br.
authors.forename: Man Chin
authors.initials: MC
authors.lastname: Chung
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP, Rodovia Araraquara Jaú Km, Araraquara, SP, 01, 14801-902, Brazil. santosjl@fcfar.unesp.br.
authors.forename: Jean Leandro
authors.initials: JL
authors.lastname: Dos Santos
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D016718:Arachidonic Acid / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006835:Hydrazones / Q000008:administration & dosage*; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006835:Hydrazones; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid