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PLoS One. 2012;7(6):e39104. doi: 10.1371/journal.pone.0039104. Epub 2012 Jun 18.

Evaluation of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole as a novel anti-inflammatory drug candidate.

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1
Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundão, Rio de Janeiro, Brasil.

Abstract

BACKGROUND:

3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing a N-O bond. The anti-inflammatory effects of this compound were studied both in vitro and in vivo.

PRINCIPAL FINDINGS:

DIC effectively decreased TNF-α and IL-6 release from LPS-stimulated macrophages in a dose dependent manner. DIC diminished the levels of COX-2 with subsequent inhibition of PGE(2) production. DIC also compromised HMGB1 translocation from the nucleus to the cytoplasm. Moreover, DIC prevented the nuclear translocation of NF-κB and inhibited the MAPK pathway. In vivo, DIC inhibited migration of neutrophils to the peritoneal cavity of mice.

CONCLUSIONS:

This study presents the potential utilization of a synthetic compound, as a lead for the development of novel anti-inflammatory drugs.

PMID:
22723938
PMCID:
PMC3377599
DOI:
10.1371/journal.pone.0039104
[Indexed for MEDLINE]
Free PMC Article
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