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

Author(s)

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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 15, n. 4, p. 17-pg., 2014-04-01.

Abstract

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)

• FAPESP's process: 11/15204-5 - Synthesis and Pharmacological Evaluation of new hybrid compounds useful to treat sickle cell disease symptoms
• Grantee: Thaís Regina Ferreira de Melo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/50359-2 - Design, synthesis and pharmacological evaluation of new hybrid drugs useful to treat hematological disorders
• Grantee: Jean Leandro dos Santos
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE