Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit
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Data
2014-04-01
Autores
Ferreira de Melo, Thais Regina [UNESP]
Chelucci, Rafael Consolin [UNESP]
Lopes Pires, Maria Elisa [UNESP]
Dutra, Luiz Antonio [UNESP]
Barbieri, Karina Pereira [UNESP]
Bosquesi, Priscila Longhin [UNESP]
Goulart Trossini, Gustavo Henrique
Chung, Man Chin [UNESP]
Santos, Jean Leandro dos [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Mdpi Ag
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.
Descrição
Palavras-chave
anti-inflammatory, analgesic, hydrazone, molecular hybridization, non-steroidal anti-inflammatory, NSAID, docking, molecular modeling, COX
Como citar
International Journal Of Molecular Sciences. Basel: Mdpi Ag, v. 15, n. 4, p. 5821-5837, 2014.