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Enhanced photosafety of cinacalcet upon complexation with serum albumin

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Enhanced photosafety of cinacalcet upon complexation with serum albumin

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dc.contributor.author Nuin Plá, Neus Edurne es_ES
dc.contributor.author Andreu Ros, María Inmaculada es_ES
dc.contributor.author Torres, Maria Jose es_ES
dc.contributor.author Jiménez Molero, María Consuelo es_ES
dc.contributor.author Miranda Alonso, Miguel Ángel
dc.date.accessioned 2016-03-07T09:59:16Z
dc.date.issued 2011-02-10
dc.identifier.issn 1520-6106
dc.identifier.uri http://hdl.handle.net/10251/61513
dc.description.abstract Cinacalcet (CIN) is a calcimimetic drug, which contains a naphthalene chromophore and binds almost quantitatively to human serum albumin (HSA). In the present work, the excited states of CIN have been characterized in order to obtain relevant information about complexation of CIN with HSA. The fluorescence spectrum in acetonitrile, at lambda(exc) = 290 nm, displayed two bands with maxima at 332 and 439 nm, assigned to the monomer and exciplex emission. Upon protonation of the amino group, the exciplex band disappeared, with a concomitant increase of the monomer emission intensity. Time-resolved fluorescence evidenced an intramolecular dynamic quenching, attributed to exciplex formation and/or photoinduced electron transfer, in agreement with the favorable thermodynamics predicted by the Rehm-Weller equations. Diffusion controlled dynamic quenching of CINH(+) fluorescence by oxygen was observed. The emission properties in PBS were similar to those obtained for CINH(+) in acetonitrile. Laser flash photolysis (LFP) of CIN and CINH(+) in aCetonitrile/N(2), at lambda(exc) = 308 nm, gave rise to the naphthalene-like triplet excited states, with maxima at 420 nm and lifetimes of 4 and 7 mu s; they were efficiently quenched by oxygen. No significant singlet excited state interaction was observed in CINH(+)/HSA complexes, as revealed by the emission spectra, which were roughly explained taking into account the relative contributions of drug and protein in the absorption spectra. Upon LFP of the complexes, triplet excited states were generated; the decays monitored at 420 nm were satisfactorily fitted using a function containing two monoexponential terms, corresponding to a Short-lived (tau(1) = 8 mu s) and a long-lived (tau(2) = 37 mu s) component. This indicates that the drug is incorporated into two different binding sites of HSA. Despite the long triplet lifetimes of the CINH(+)/HSA complexes, the rate constant of quenching by oxygen was found to be 2 orders of magnitude lower than that determined in acetonitrile, which can be attributed to the relative slower diffusion rates in this microheterogeneous system. Therefore, the protein microenvironment protects cinacalcet from attack by oxygen; this prevents the phototoxic effects caused by formation of singlet oxygen and results in an enhanced photosafety of the drug. es_ES
dc.description.sponsorship Financial support from the MICINN (Grant CTQ2007-67010), from the Generalitat Valenciana (Prometeo Program, ref 2008/090) and from Carlos III Institute of Health (Grant RIRAAF, RETICS program) is gratefully acknowledged. en_EN
dc.language Inglés es_ES
dc.publisher American Chemical Society es_ES
dc.relation MICINN CTQ2007-67010 es_ES
dc.relation Generalitat Valenciana 2008/090 es_ES
dc.relation Carlos III Institute of Health es_ES
dc.relation.ispartof Journal of Physical Chemistry B es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject CALCIMIMETIC AGENT CINACALCET es_ES
dc.subject RENAL-TRANSPLANT PATIENTS es_ES
dc.subject SINGLET MOLECULAR-OXYGEN es_ES
dc.subject PARATHYROID CARCINOMA es_ES
dc.subject STATE INTERACTIONS es_ES
dc.subject CHARGE-TRANSFER es_ES
dc.subject EXCITED-STATE es_ES
dc.subject MODEL DYADS es_ES
dc.subject DRUG es_ES
dc.subject HYPERPARATHYROIDISM es_ES
dc.subject.classification QUIMICA ORGANICA es_ES
dc.title Enhanced photosafety of cinacalcet upon complexation with serum albumin es_ES
dc.type Artículo es_ES
dc.embargo.lift 10000-01-01
dc.embargo.terms forever es_ES
dc.identifier.doi 10.1021/jp1069576
dc.rights.accessRights Cerrado es_ES
dc.contributor.affiliation Universitat Politècnica de València. Instituto Universitario Mixto de Tecnología Química - Institut Universitari Mixt de Tecnologia Química es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Química - Departament de Química es_ES
dc.description.bibliographicCitation Nuin Pla, NE.; Andreu Ros, MI.; Torres, MJ.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2011). Enhanced photosafety of cinacalcet upon complexation with serum albumin. Journal of Physical Chemistry B. 115(5):1158-1164. doi:10.1021/jp1069576 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://dx.doi.org/10.1021/jp1069576 es_ES
dc.description.upvformatpinicio 1158 es_ES
dc.description.upvformatpfin 1164 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 115 es_ES
dc.description.issue 5 es_ES
dc.relation.senia 39789 es_ES


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