Browsing by Author "Zúñiga Núñez, Daniel"

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    Direct Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies
    (2023) Mariño Ocampo, Nory Johana; Rodríguez Sánchez, Diego Fernando; Daniel Sebastian, Guerra Diaz; Zúñiga Núñez, Daniel; Duarte, Yorley; Fuentealba Patiño, Denis Alberto; Zacconi, Flavia C. M.
    Direct 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.
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    Fatty Acid Conjugates of Toluidine Blue O as Amphiphilic Photosensitizers: Synthesis, Solubility, Photophysics and Photochemical Properties(dagger)
    (2021) Robinson Duggon, José Luis; Pizarro, Nancy; Gunthe, Germán; Zúñiga Núñez, Daniel; Edwards M., Ana María; Greer, Alexander; Fuentealba Patiño, Denis Alberto
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    Reaction Kinetics of Phenolic Antioxidants Toward Photo-induced Pyranine Free Radicals in Biological Models
    (2017) Aspée, Alexis; Aliaga, Christian; Maretti, Luca; Zúñiga Núñez, Daniel; Godoy, Jessica; Pino, Eduardo; Cárdenas Jirón, Gloria; López Alarcón, Camilo Ignacio; Scaiano, Juan C.; Alarcón Abarzúa, Emilio Isaac
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    Time-resolved fluorescence and anisotropy-sensitive 1,2-dimyristoyl-sn-glycero-3-(7-aminocoumarin) phosphoetanolamide probe for studying membrane lipid domains
    (ELSEVIER SCI LTD, 2023) Zúñiga Núñez, Daniel; Mura, Francisco; Mariño-Ocampo, Nory; Briones-Rebolledo, Patricio; Poblete, Horacio; Mallet, Jean-Maurice; Fuentealba Patino, Denis Alberto; Aspee, Alexis
    A fluorescent probe C-DMPE was synthesised to monitor interfacial membrane properties by conjugating coumarin-343 and 1,2-dimyristoyl-sn-glycero-3-phosphorylethanolamine (DMPE), anchoring the 7-aminocou-marin moiety close to the phospholipid polar head at the membrane interface. Large unilamellar vesicles (LUV) of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), of 1,2-dioleyl-sn-glycero-3-phosphatidyl-choline (DOPC) and cholesterol were employed as a model of lipid bilayer. Time-resolved fluorescence developed an emissive Internal Charge Transfer excited state with a long fluorescence lifetime (T1), a Locally Excited state with an intermediate fluorescence lifetime (T2), and a short lifetime (T3) associated with an intermolecular quenching by interaction with a phosphate group of neighbour phospholipids, as is clearly shown by molecular dynamics simulations. Shorter values of fluorescence lifetimes T1 and T3 were observed in DOPC with respect to DPPC, responding to a more fluid membrane with more significant water accessibility in DOPC than DPPC. However, in DPPC:DOPC vesicles, these fluorescence lifetimes are even shorter, allowing to be attributed to favourable sensing of boundary limit lipid domains. In similitude, time-resolved anisotropy showed shorter rotational correlation times phi 1, in DPPC: DOPC vesicles than in DOPC associated with a faster internal rotational movement of the 7-aminocoumarin group in domains than in fluid a DOPC membrane. In addition, shorter rotational correlation times, (P2, were also observed in DPPC:DOPC vesicles compared to DPPC, suggesting a faster lateral diffusion of the probe in the presence of domains.