Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

Autor(es)

Ferreira de Melo, Thais Regina ; Chelucci, Rafael Consolin ; Lopes Pires, Maria Elisa ; Dutra, Luiz Antonio ; Barbieri, Karina Pereira ; Bosquesi, Priscila Longhin ; Goulart Trossini, Gustavo Henrique ; Chung, Man Chin ; dos Santos, Jean Leandro

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 15, n. 4, p. 17-pg., 2014-04-01.

Resumo

A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a-e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a-e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a-e are less gastrotoxic than the respective parent drug. Compounds 4b-e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a-b and 4d-e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a-e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non- steroidal anti-inflammatory drugs. (AU)

• 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
• 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