Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-acyl hydrazone subunit.

Autor: de Melo TR; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. trfmelo@gmail.com., Chelucci RC; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. rafaelchelucci@hotmail.com., Pires ME; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. mariaelisalopes@yahoo.com.br., Dutra LA; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. luizdutra_qf@yahoo.com.br., Barbieri KP; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. kakabarbieri85@yahoo.com.br., Bosquesi PL; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. bosquesi@fcfar.unesp.br., Trossini GH; Faculty of Pharmaceutical Science, University of São Paulo, Av. Professor Lineu Prestes 580, São Paulo 05508-900, SP, Brazil. gustavo.trossini@gmail.com., Chung MC; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. chungmc@fcfar.unesp.br., dos Santos JL; School of Pharmaceutical Science, State University of São Paulo (UNESP), Rodovia Araraquara Jaú Km. 01, Araraquara, São Paulo 14801-902, Brazil. santosjl@fcfar.unesp.br.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2014 Apr 04; Vol. 15 (4), pp. 5821-37. Date of Electronic Publication: 2014 Apr 04.
DOI: 10.3390/ijms15045821
Abstrakt: 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.
Databáze: MEDLINE
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