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


RESULTS
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.
Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundão, Rio de Janeiro, Brasil.
Amanda Roberta Revoredo
AR
Vicentino
Vitor Coutinho
VC
Carneiro
Anderson de Mendonça
Ade M
Amarante
Claudia Farias
CF
Benjamim
Alcino Palermo
AP
de Aguiar
Marcelo Rosado
MR
Fantappié
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D007555:Isoxazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D011725:Pyridines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D015398:Signal Transduction; D013864:Thioglycolates / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C576642:3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole; D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; D015850:Interleukin-6; D007555:Isoxazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone