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

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dc.contributor.author Correa, Michelle Fidelis [UNIFESP]
dc.contributor.author Varela, Marina Themoteo [UNIFESP]
dc.contributor.author Balbino, Aleksandro Martins [UNIFESP]
dc.contributor.author Torrecilhas, Ana Claudia [UNIFESP]
dc.contributor.author Landgraf, Richardt Gama [UNIFESP]
dc.contributor.author Paolo Troncone, Lanfranco Ranieri
dc.contributor.author dos Santos Fernandes, Joao Paulo [UNIFESP]
dc.date.accessioned 2019-08-19T11:50:20Z
dc.date.available 2019-08-19T11:50:20Z
dc.date.issued 2017
dc.identifier http://dx.doi.org/10.1111/cbdd.12947
dc.identifier.citation Chemical Biology & Drug Design. Hoboken, v. 90, n. 2, p. 317-322, 2017.
dc.identifier.issn 1747-0277
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/51517
dc.description.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. en
dc.description.sponsorship Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 317-322
dc.language.iso eng
dc.publisher Wiley
dc.rights Acesso restrito
dc.subject anti-inflammatory agent en
dc.subject asthma en
dc.subject H3R ligand en
dc.subject H4R ligand en
dc.subject histamine receptor en
dc.title 1-[(2,3-Dihydro-1-benzofuran-2-yl) methyl]piperazines as novel anti-inflammatory compounds: Synthesis and evaluation on H3R/H4R en
dc.type Artigo
dc.description.affiliation Univ Fed São Paulo, Dept Ciencias Farmaceut, Diadema, SP, Brazil
dc.description.affiliation Inst Butantan, São Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed São Paulo, Dept Ciencias Farmaceut, Diadema, SP, Brazil
dc.description.sponsorshipID FAPESP: 2013/18897-7
dc.description.sponsorshipID FAPESP: 2013/20479-9
dc.description.sponsorshipID FAPESP: 2014/16564-3
dc.description.sponsorshipID CNPq: 455411/2014-0
dc.identifier.doi 10.1111/cbdd.12947
dc.description.source Web of Science
dc.identifier.wos WOS:000405102900015



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