期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 58, 期 -, 页码 117-127出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2012.10.010
关键词
Coumarin; Anti-inflammatory; Neutrophils; Molecular docking; 3-(Triazolyl)-coumarins; Click chemistry; iNOS
资金
- FAPESP [07/59404-2, 2010/15677-8]
- CAPES [808/2009]
- CNPq [300613/2007-5, 130599/2009-3, 677-2011-5, 308116/2010-0, 306532/2009-3]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [10/15677-8] Funding Source: FAPESP
A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-alpha secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that it pi center dot center dot center dot pi interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored. (C) 2012 Elsevier Masson SAS. All rights reserved.
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