Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations

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dc.contributor.authorSantos, Mariana Bastos dos [UNESP]
dc.contributor.authorCarvalho Marques, Beatriz [UNESP]
dc.contributor.authorMiranda Ayusso, Gabriela [UNESP]
dc.contributor.authorRocha Garcia, Mayara Aparecida [UNESP]
dc.contributor.authorChiquetto Paracatu, Luana [UNESP]
dc.contributor.authorPauli, Ivani
dc.contributor.authorSilva Bolzani, Vanderlan [UNESP]
dc.contributor.authorDefini Andricopulo, Adriano
dc.contributor.authorFarias Ximenes, Valdecir [UNESP]
dc.contributor.authorZeraik, Maria Luiza
dc.contributor.authorRegasini, Luis Octavio [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual de Londrina (UEL)
dc.date.accessioned2021-06-25T10:55:34Z
dc.date.available2021-06-25T10:55:34Z
dc.date.issued2021-05-01
dc.description.abstractIn the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC50 value of 0.53 and 19.2 µM, respectively. Potent ex vivo MPO inhibitors 5, 8 and 9 were not toxic to human neutrophils at 50 µM, as well as displayed weak 2,2-diphenyl-1-pycrylhydrazyl radical (DPPH•) and hypochlorous acid (HOCl) scavenger abilities. Docking simulations indicated binding mode of MPO inhibitors, evidencing hydrogen bonds between the amino group at 4′position (ring A) of chalcones with Gln91, Asp94, and Hys95 MPO residues. In this regard, the efficacy and low toxicity promoted aminochalcones and arylic analogues to the rank of hit compounds in the search for new non-steroidal anti-inflammatory compounds.en
dc.description.affiliationInstitute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)
dc.description.affiliationDepartment of Chemistry Faculty of Sciences São Paulo State University (UNESP)
dc.description.affiliationPhysics Institute of São Carlos University of São Paulo
dc.description.affiliationDepartment of Organic Chemistry Institute of Chemistry São Paulo State University
dc.description.affiliationDepartment of Chemistry State University of Londrina (UEL)
dc.description.affiliationUnespInstitute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Chemistry Faculty of Sciences São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Organic Chemistry Institute of Chemistry São Paulo State University
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.identifierhttp://dx.doi.org/10.1016/j.bioorg.2021.104773
dc.identifier.citationBioorganic Chemistry, v. 110.
dc.identifier.doi10.1016/j.bioorg.2021.104773
dc.identifier.issn1090-2120
dc.identifier.issn0045-2068
dc.identifier.scopus2-s2.0-85102643721
dc.identifier.urihttp://hdl.handle.net/11449/207465
dc.language.isoeng
dc.relation.ispartofBioorganic Chemistry
dc.sourceScopus
dc.subjectChalcone
dc.subjectIn silico
dc.subjectIn vitro
dc.subjectMyeloperoxidase (MPO)
dc.subjectStructure-activity relationship (SAR)
dc.titleChalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigationsen
dc.typeArtigo

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