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评估 3-(3-氯苯基)-5-(4-吡啶基)-4,5-二氢异恶唑作为一种新型抗炎药物候选物。

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

机构信息

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

出版信息

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

DOI:10.1371/journal.pone.0039104
PMID:22723938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3377599/
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.

摘要

背景

3-(3-氯苯基）-5-(4-吡啶基）-4,5-二氢异恶唑（DIC）是一种含有 N-O 键的五元杂环化合物。该化合物的抗炎作用已在体外和体内进行了研究。

主要发现

DIC 可有效降低 LPS 刺激的巨噬细胞中 TNF-α 和 IL-6 的释放，呈剂量依赖性。DIC 降低 COX-2 的水平，从而抑制 PGE（2）的产生。DIC 还可使 HMGB1 从核内易位至细胞质。此外，DIC 可阻止 NF-κB 的核易位并抑制 MAPK 途径。在体内，DIC 抑制了中性粒细胞向小鼠腹腔的迁移。

结论

本研究提出了一种合成化合物的潜在应用，可作为开发新型抗炎药物的先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/cb772b07bdd1/pone.0039104.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/604c8c55b842/pone.0039104.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/455fab788bd8/pone.0039104.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/cb772b07bdd1/pone.0039104.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/604c8c55b842/pone.0039104.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/d37f5541b897/pone.0039104.g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a812/3377599/cb772b07bdd1/pone.0039104.g008.jpg

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