Publicaciones 2011-2020

@article{RN337,
title = {Rosmarinic Acid Prevents Fibrillization and Diminishes Vibrational Modes Associated to Beta Sheet in Tau Protein Linked to Alzheimer's Disease},
author = { A. Cornejo and F.A. Sandoval and L. Caballero and L. Machuca and P. Munoz and J. Caballero and G. Perry and A. Ardiles and C. Areche and F. Melo},
url = {/brokenurl#<Go to ISI>://WOS:000406130000006},
doi = {10.1080/14756366.2017.1347783},
issn = {1475-6366},
year = {2017},
date = {2017-01-01},
journal = {Journal of Enzyme Inhibition and Medicinal Chemistry},
volume = {32},
number = {1},
pages = {945-953},
abstract = {Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-beta plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents beta-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and beta sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid.},
keywords = {alzheimer's amyloid beta-sheet, carnosic cells criteria, disease, fibril filaments, formation, helical in-vitro, inhibition, inhibitors, mice, neuropathologic paired pharmacophore, salvia-officinalis, tau transgenic},
pubstate = {published},
tppubtype = {article}
}

@article{RN346,
title = {Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe2+/Cu2+ Chelator in Cell and Animal Models of Parkinson's Disease},
author = { P. Aguirre and O. Garcia-Beltran and V. Tapia and Y. Munoz and B.K. Cassels and M. Nunez},
url = {/brokenurl#<Go to ISI>://WOS:000392459400021},
doi = {10.1021/acschemneuro.6b00309},
issn = {1948-7193},
year = {2017},
date = {2017-01-01},
journal = {Acs Chemical Neuroscience},
volume = {8},
number = {1},
pages = {178-185},
abstract = {Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson's disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ similar to Fe2+ > Zn2+ > Fe3+. No binding capacity was detected for Hg2+, co(2+), ca(2+), Mnz+, Mg2+, Ni2+, Pb2+ or Cd2+. DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY581/891. DHC12 also blocked the decrease in mitochondrial membrane potential, detected by tetrarnethylrhodamine distribution. DHC12 inhibited MAO-A and MAO-B activity. Oral administration of DHC12 to mice (0.25 mg/kg body weight) protected substantia nigra pars compacta (SNpc) neurons against MPTP-induced death. Taken together, our results support the concept that DHC12 is a mitochondrial-targeted neuroprotective iron-copper chelator and MAO-B inhibitor with potent antioxidant and mitochondria protective activities. Oral administration of low doses of DHC12 is a promising therapeutic strategy for the treatment of diseases with a mitochondrial iron accumulation component, such as PD.},
keywords = {activity, antioxidant antioxidant, basal brain chelator, complex content, coumarin-based coumarins, disease, ganglia, i, inhibitory-activity, iron iron-copper lipid-peroxidation, model, mouse neurodegeneration neurodegeneration, neuroprotection, niptp oxidative parkinsons stress, with},
pubstate = {published},
tppubtype = {article}
}

@article{RN243,
title = {The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death},
author = { N.P. Mena and O. Garcia-Beltran and F. Lourido and P.J. Urrutia and R. Mena and V. Castro-Castillo and B.K. Cassels and M. Nunez},
url = {/brokenurl#<Go to ISI>://WOS:000358455300051},
doi = {10.1016/j.bbrc.2015.06.014},
issn = {0006-291x},
year = {2015},
date = {2015-01-01},
journal = {Biochemical and Biophysical Research Communications},
volume = {463},
number = {4},
pages = {787-792},
publisher = {2015 Elsevier Inc.},
abstract = {Abundant evidence indicates that iron accumulation, oxidative damage and mitochondrial dysfunction are common features of Huntington's disease, Parkinson's disease, Friedreich's ataxia and a group of disorders known as Neurodegeneration with Brain Iron Accumulation. In this study, we evaluated the effectiveness of two novel 8-OH-quinoline-based iron chelators, Q1 and Q4, to decrease mitochondrial iron accumulation and oxidative damage in cellular and animal models of PD. We found that at sub-micromolar concentrations, Q1 selectively decreased the mitochondrial iron pool and was extremely effective in protecting against rotenone-induced oxidative damage and death. Q4, in turn, preferentially chelated the cytoplasmic iron pool and presented a decreased capacity to protect against rotenone-induced oxidative damage and death. Oral administration of Q1 to mice protected substantia nigra pars compacta neurons against oxidative damage and MPTP-induced death. Taken together, our results support the concept that oral administration of Q1 is a promising therapeutic strategy for the treatment of NBIA.},
keywords = {brain chelation, contributes, degeneration, disease, diseases, homeostasis, hydroxyquinolines, in-vivo, inhibition iron iron, mitochondria, neurodegenerative parkinson's parkinsons-disease, substantia-nigra},
pubstate = {published},
tppubtype = {article}
}

@article{RN244,
title = {Molecular Dynamics Simulation of Halogen Bonding Mimics Experimental Data for Cathepsin L Inhibition},
author = { C. Celis-Barros and L. Saavedra-Rivas and J.C. Salgado and B.K. Cassels and G. Zapata-Torres},
url = {/brokenurl#<Go to ISI>://WOS:000346913200004},
doi = {10.1007/s10822-014-9802-7},
issn = {0920-654x},
year = {2015},
date = {2015-01-01},
journal = {Journal of Computer-Aided Molecular Design},
volume = {29},
number = {1},
pages = {37-46},
abstract = {A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogenated inhibitors. Our results show that chloro, bromo and iodo derivatives have progressively narrower distributions of calculated geometries, which reflects the order of affinity I > Br > Cl, in agreement with the IC50 values. Graphs for the Cl, Br and I analogs show stable interactions between the halogen atom and the Gly61 carbonyl oxygen of the enzyme. The halogen-oxygen distance is close to or less than the sum of the van der Waals radii; the C-X center dot center dot center dot O angle is about 170A degrees; and the X center dot center dot center dot O=C angle approaches 120A degrees, as expected for halogen bond formation. In the case of the iodo-substituted analogs, these effects are enhanced by introduction of a fluorine atom on the inhibitors' halogen-bonding phenyl ring, indicating that the electron withdrawing group enlarges the sigma-hole, resulting in improved halogen bonding properties.},
keywords = {atherosclerosis, bonding, bromine cathepsin cathepsins, cysteine design, discovery, disease, drug force-field, halogen halogenated inhibitors, interactions, l, md optimization, protein-ligand sigma-hole, simulation},
pubstate = {published},
tppubtype = {article}
}

@article{RN195,
title = {Substituent Effects on Reactivity of 3-Cinnamoylcoumarins with Thiols of Biological Interest},
author = { M.E. Aliaga and W. Tiznado and B.K. Cassels and M. Nunez and D. Millan and E.G. Perez and O. Garcia-Beltran and P. Pavez},
url = {/brokenurl#<Go to ISI>://WOS:000327849700027},
doi = {10.1039/c3ra44695f},
issn = {2046-2069},
year = {2014},
date = {2014-01-01},
journal = {Rsc Advances},
volume = {4},
number = {2},
pages = {697-704},
abstract = {The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, gamma-glutamylcysteine and glutathione with 3-cinnamoylcoumarin derivatives (ChC1-ChC4) in aqueous solution (30 degrees C, ionic strength 0.2 M KCI) were followed fluorimetrically and evaluated kinetically. The study was completed with a theoretical analysis based on the inverse of the Fukui potential (1/v(f) (r)), which is proposed for the first time as a local softness descriptor. Thus, considering both experimental results and theoretical analysis, the following conclusions can be drawn: (i) the reactivity of the tested probes towards Michael addition increases in the para-substitution sequence: H < OEt < SMe < Br < NO2, and is not correlated with the sigma(P) values of the substituents; (ii) in turn, the descriptor proposed here as local softness (1/v(f) (r)) appears as a promising reactivity index that is able to explain the higher k(N) values found for both electron-withdrawing and electron-donating groups; (iii) the nucleophilic reactivity of the biothiols employed increases in the sequence Cys-Gly < Hcy < GSH < Cys < gamma-Glu-Cys; and also finally (iv) we have demonstrated that these probes can be used for fluorimetric thiol determination in SH-SY5Y cells.},
keywords = {alpha, beta-unsaturated chemical-reactivity, cysteine, density-functional-approach, disease, electrophilicity fluorescent, glutathione, ketones, michael probe, turn-on},
pubstate = {published},
tppubtype = {article}
}

@article{RN17e,
title = {The Development of a Fluorescence Turn-on Sensor for Cysteine, Glutathione and Other Biothiols. A Kinetic Study},
author = { O. Garcia-Beltran and N. Mena and E.G. Perez and B.K. Cassels and M. Nunez and F. Werlinger and D. Zavala and M.E. Aliaga and P. Pavez},
url = {/brokenurl#<Go to ISI>://WOS:000297442400022},
doi = {10.1016/j.tetlet.2011.09.137},
issn = {0040-4039},
year = {2011},
date = {2011-01-01},
journal = {Tetrahedron Letters},
volume = {52},
number = {49},
pages = {6606-6609},
publisher = {2011 Elsevier Ltd.},
abstract = {Two fluorescence probes for the detection of cysteine (Cys), glutathione (GSH) and other biothiols, such as homocysteine (Hcy) and cysteinyl-glycine (Cys-Gly), were developed. These molecular probes are coumarin-based derivatives containing a chalcone-like moiety that reacts with biothiols through a Michael addition reaction, leading to strong fluorescence enhancements. The reactivity of the tested biothiols toward both probes (ChC1 and ChC2) follows the order Cys > GSH > Hcy > Cys-Gly, ChC1 being less reactive than ChC2. Possible interference with other amino acids was assessed. ChC1 and ChC2 display a highly selective fluorescence enhancement with thiols, allowing these probes to be used for fluorimetric thiol determination in SH-SY5Y cells.},
keywords = {addition, biothiols, coumarin-based derivatives, disease, fluorescence homocysteine, michael probe, probes, thiols, water},
pubstate = {published},
tppubtype = {article}
}

@article{RN19h,
title = {Esr, Electrochemical, Molecular Modeling and Biological Evaluation of 4-Substituted and 1,4-Disubstituted 7-Nitroquinoxalin-2-Ones as Potential Anti-Trypanosoma Cruzi Agents},
author = { B. Aguilera-Venegas and C. Olea-Azar and E. Norambuena and V.J. Aran and F. Mendizabal and M. Lapier and J.D. Maya and U. Kemmerling and R. Lopez-Munoz},
url = {/brokenurl#<Go to ISI>://WOS:000288046600012},
doi = {10.1016/j.saa.2010.12.017},
issn = {1386-1425},
year = {2011},
date = {2011-01-01},
journal = {Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy},
volume = {78},
number = {3},
pages = {1004-1012},
publisher = {2010 Elsevier B.V.},
abstract = {Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action.},
keywords = {anion, behavior binding-site, chagas chagas-disease, complexes, crystal-structure, disease, epimastigote, esr, glutathione-reductase, modeling, molecular nifurtimox, nitro nitroquinoxaline, radical-anion, reductase, superoxide trypanothione trypomastigote},
pubstate = {published},
tppubtype = {article}
}