Computational Strategies Targeting Inhibition of Helicobacter pylori and Cryptococcus neoformans Ureases

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dc.contributor.authorFabris, Marciéli
dc.contributor.authorNascimento-Júnior, Nailton M. [UNESP]
dc.contributor.authorBispo, Marcelle L. F.
dc.contributor.authorCamargo, Priscila G.
dc.contributor.institutionUniversidade Estadual de Londrina (UEL)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:55:27Z
dc.date.available2023-07-29T13:55:27Z
dc.date.issued2023-01-01
dc.description.abstractHelicobacter pylori and Cryptococcus ssp. are pathogenic ureolytic microorganisms that cause several disorders in the host organism and, in severe cases, lead to death. Both infections have the urease enzyme as a key virulence factor since they use its ability to produce ammonia to soften the inhospitable pH to which they are subjected. In this review, we describe two ureases as possible molecular targets for drug discovery and provide insights for developing potent inhibitors against ureases from these pathogenic microorganisms through computer-aided drug discovery approaches, such as structure-based drug design (SBDD) and structure-activity relationship (SAR). The SAR studies have indicated several essential subunits and groups to be present in ure-ase inhibitors that are critical for inhibitory activity against H. pylori or Cryptococcus spp. Since the three-dimensional structure of C. neoformans urease has yet to be determined experimentally, the plant urease of Canavalia ensiformis was used in this study due to its structural similarity. Therefore, in the SBDD context, FTMap and FTSite analyses were performed to reveal characteristics of the urease active sites in two protein data bank files (4H9M, Canavalia ensiformis, and 6ZJA, H. pylori). Finally, a docking-based analysis was performed to explore the best inhibitors described in the literature to understand the role of the ligand interactions with the key residues in complex ligand-urease stabilization, which can be applied in the design of novel bioac-tive compounds.en
dc.description.affiliationChemistry Department Laboratory of Synthesis of Medicinal Molecules (LaSMMed) State University of Londrina (UEL), Celso Garcia CID Road, Campus Universitário, Paraná
dc.description.affiliationDepartment of Biochemistry and Organic Chemistry Laboratory of Medicinal Chemistry Organic Synthesis and Molecular Modeling (LaQMedSOMM) Institute of Chemistry São Paulo State University (Unesp), Professor Francisco Degni Street, 55, Jardim Quitandinha, SP
dc.description.affiliationUnespDepartment of Biochemistry and Organic Chemistry Laboratory of Medicinal Chemistry Organic Synthesis and Molecular Modeling (LaQMedSOMM) Institute of Chemistry São Paulo State University (Unesp), Professor Francisco Degni Street, 55, Jardim Quitandinha, SP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdCAPES: 01
dc.description.sponsorshipIdFAPESP: 2018/00187-7
dc.format.extent777-792
dc.identifierhttp://dx.doi.org/10.2174/1381612829666230329122902
dc.identifier.citationCurrent Pharmaceutical Design, v. 29, n. 10, p. 777-792, 2023.
dc.identifier.doi10.2174/1381612829666230329122902
dc.identifier.issn1873-4286
dc.identifier.issn1381-6128
dc.identifier.scopus2-s2.0-85159732958
dc.identifier.urihttp://hdl.handle.net/11449/248851
dc.language.isoeng
dc.relation.ispartofCurrent Pharmaceutical Design
dc.sourceScopus
dc.subjectCanavalia ensiformis
dc.subjectcryptococcosis
dc.subjectDrug discovery
dc.subjectmolecular docking
dc.subjectstructure-activity relationship
dc.subjecturease inhibitors
dc.subjectureolytic microorganisms
dc.subjectvirulence factor
dc.titleComputational Strategies Targeting Inhibition of Helicobacter pylori and Cryptococcus neoformans Ureasesen
dc.typeResenha

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