1-[(2,3-Dihydro-1-benzofuran-2-yl) methyl]piperazines as novel anti-inflammatory compounds: Synthesis and evaluation on H3R/H4R

1-[(2,3-Dihydro-1-benzofuran-2-yl) methyl]piperazines as novel anti-inflammatory compounds: Synthesis and evaluation on H3R/H4R

Author Correa, Michelle Fidelis Autor UNIFESP Google Scholar
Varela, Marina Themoteo Autor UNIFESP Google Scholar
Balbino, Aleksandro Martins Autor UNIFESP Google Scholar
Torrecilhas, Ana Claudia Autor UNIFESP Google Scholar
Landgraf, Richardt Gama Autor UNIFESP Google Scholar
Paolo Troncone, Lanfranco Ranieri Google Scholar
dos Santos Fernandes, Joao Paulo Autor UNIFESP Google Scholar
Abstract The histamine receptors (HRs) are members of G-protein-coupled receptor superfamily and traditional targets of huge therapeutic interests. Recently, H3R and H4R have been explored as targets for drug discovery, including in the search for dual-acting H3R/H4R ligands. The H4R, the most recent histamine receptor, is a promising target for novel anti-inflammatory agents in several conditions such as asthma and other chronic inflammatory diseases. Due to similarity with previously reported ligands of HRs, a set of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines were synthesized and evaluated in competitive binding assays as H3R/H4R ligands herein. The results showed the compounds presented affinity (K-i) for H3R/H4R in micromolar range, and they are more selective to H3R. All the compounds showed no important cytotoxicity to mammalian cells. The phenyl-substituted compound LINS01005 has shown the higher affinity of the set for H4R, but no considerable selectivity toward this receptor over H3R. LINS01005 showed interesting anti-inflammatory activity in murine asthma model, reducing the eosinophil counts in bronchoalveolar lavage fluid, as well as the COX-2 expression. The presented compounds are valuable prototypes for further improvements to achieve better anti-inflammatory agents.
Keywords anti-inflammatory agent
H3R ligand
H4R ligand
histamine receptor
Language English
Sponsor Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2013/18897-7
FAPESP: 2013/20479-9
FAPESP: 2014/16564-3
CNPq: 455411/2014-0
Date 2017
Published in Chemical Biology & Drug Design. Hoboken, v. 90, n. 2, p. 317-322, 2017.
ISSN 1747-0277 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 317-322
Origin http://dx.doi.org/10.1111/cbdd.12947
Access rights Closed access
Type Article
Web of Science ID WOS:000405102900015
URI http://repositorio.unifesp.br/handle/11600/51517

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