Direct Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies

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dc.catalogadordfo
dc.contributor.authorMariño Ocampo, Nory Johana
dc.contributor.authorRodríguez Sánchez, Diego Fernando
dc.contributor.authorDaniel Sebastian, Guerra Diaz
dc.contributor.authorZúñiga Núñez, Daniel
dc.contributor.authorDuarte, Yorley
dc.contributor.authorFuentealba Patiño, Denis Alberto
dc.contributor.authorZacconi, Flavia C. M.
dc.date.accessioned2023-08-22T20:38:48Z
dc.date.available2023-08-22T20:38:48Z
dc.date.issued2023
dc.description.abstractDirect FXa inhibitors are an important class of bioactive molecules (rivaroxaban, apixaban,edoxaban, and betrixaban) applied for thromboprophylaxis in diverse cardiovascular pathologies.The interaction of active compounds with human serum albumin (HSA), the most abundant protein inblood plasma, is a key research area and provides crucial information about drugs’ pharmacokineticsand pharmacodynamic properties. This research focuses on the study of the interactions betweenHSA and four commercially available direct oral FXa inhibitors, applying methodologies includingsteady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and moleculardynamics. The HSA complexation of FXa inhibitors was found to occur via static quenching, and thecomplex formation in the ground states affects the fluorescence of HSA, with a moderate bindingconstant of 104 M−1. However, the ITC studies reported significantly different binding constants (103 M−1) compared with the results obtained through spectrophotometric methods. The suspectedbinding mode is supported by molecular dynamics simulations, where the predominant interactionswere hydrogen bonds and hydrophobic interactions (mainly π–π stacking interactions between thephenyl ring of FXa inhibitors and the indole moiety of Trp214). Finally, the possible implications ofthe obtained results regarding pathologies such as hypoalbuminemia are briefly discussed.
dc.fechaingreso.objetodigital2023-08-22
dc.fuente.origenORCID
dc.identifier.doi10.3390/ijms24054900
dc.identifier.eissn1422-0067
dc.identifier.issn1422-0067
dc.identifier.urihttps://doi.org/10.3390/ijms24054900
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/74456
dc.information.autorucEscuela de Química ; Mariño Ocampo, Nory Johana ; 0000-0003-2013-9790 ; 1059618
dc.information.autorucEscuela de Química ; Rodríguez Sanchéz Diego Fernando ; 0000-0003-0954-9481 ; 1059619
dc.information.autorucEscuela de Química ; Daniel Sebastian, Guerra Diaz ; S/I ; 1082306
dc.information.autorucEscuela de Química ; Fuentealba Patiño, Denis Alberto ; 0000-0003-4798-7204 ; 160255
dc.information.autorucEscuela de Química ; Zacconi Flavia, Cristina Milagro ; 0000-0002-3676-0453 ; 1011127
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final16
dc.pagina.inicio1
dc.revistaInternational Journal of Molecular Science
dc.rightsacceso abierto
dc.subjectFXa inhibitors
dc.subjecthuman serum albumin
dc.subjectfluorescence
dc.subjectisothermal titration calorimetry
dc.subjectmolecular modeling
dc.subjectdirect oral FXa inhibitors
dc.subjectcommercially available FXa inhibitors
dc.subjectapixaban
dc.subjectrivaroxaban
dc.subjectedoxaban
dc.subjectbetrixaban
dc.subject.ddc510
dc.subject.deweyMatemática física y químicaes_ES
dc.titleDirect Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies
dc.typeartículo
dc.volumen24
sipa.codpersvinculados1059618
sipa.codpersvinculados1059619
sipa.codpersvinculados1082306
sipa.codpersvinculados160255
sipa.codpersvinculados1011127
sipa.trazabilidadORCID;2023-08-21
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