Publicaciones 2011-2020

@article{RN322,
title = {Small Structural Changes on a Hydroquinone Scaffold Determine the Complex I Inhibition or Uncoupling of Tumoral Oxidative Phosphorylation},
author = { F.A. Urra and M. Cordova-Delgado and M. Lapier and A. Orellana-Manzano and L. Acevedo-Arevalo and H. Pessoa-Mahana and J.M. Gonz\'{a}lez-Vivanco and M. Martinez-Cifuentes and O. Ramirez-Rodriguez and J.P. Millas-Vargas and B. Weiss-Lopez and M. Pavani and J. Ferreira and R. Araya-Maturana},
url = {/brokenurl#<Go to ISI>://WOS:000378100100006},
doi = {10.1016/j.taap.2015.12.005},
issn = {0041-008x},
year = {2016},
date = {2016-01-01},
journal = {Toxicology and Applied Pharmacology},
volume = {291},
pages = {46-57},
publisher = {2015 Elsevier Inc},
abstract = {Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3(ADP)), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells.},
keywords = {anti-cancer apoptosis, calu-6 cancer-cells, cell cells, complex derivatives, dysfunction, energy-metabolism, hydroquinones, i, liver-mitochondria, mitochondrial oxidative phosphorylation, respiration, ta3, uncouplers},
pubstate = {published},
tppubtype = {article}
}

@article{RN100,
title = {Location, Orientation and Dynamics of Two Molecules with Mitochondrial Activity Dissolved in Anionic Lyomesophase. A H-2-Nmr and Md Study},
author = { V.E. Bahamonde-Padilla and M. Martinez-Cifuentes and D. Munoz-Masson and A.I. Ruiz and H. Ahumada and R. Araya-Maturana and J. Soto-Delgado and B. Weiss-Lopez},
url = {/brokenurl#<Go to ISI>://WOS:000309315300021},
doi = {10.4067/S0717-97072012000300021},
issn = {0717-9707},
year = {2012},
date = {2012-01-01},
journal = {Journal of the Chilean Chemical Society},
volume = {57},
number = {3},
pages = {1295-1300},
abstract = {4,4-Dimethyl-5,8-dihydroanthracene-1,9,10(4H)-trione (Q1) and 9,10-Dihydroxy-4,4-dimethyl-5,8-dihydro-1 (4H)-anthracenone (Q2), two molecules that inhibit cancer cell respiration, were selectively deuterated and dissolved in an anionic discotic nematic lyotropic liquid crystal (dnllc) solution. The solution provides a magnetic field oriented anisotropic medium, where the location, average orientation and dynamics of Q(1) and Q(2) were examined by measuring H-2-NMR quadrupole splittings (Delta v(Q)) and H-2 longitudinal relaxation times (T-1). The NMR data shows that both molecules are strongly attached to the aggregate and, when dissolved, increase the alignment of the interface components with the magnetic field. However they present different average orientations. To assist with the interpretation of the experimental results, 300ns Molecular Dynamics (MD) trajectories of a bilayer model of the aggregate were calculated. The results show that both molecules spontaneously diffuse inside the bilayer, to locate in the limit between the hydrophobic core and the interface. The orientations of both molecules in the aggregate are determined by the formation of H-bonds with water.},
keywords = {antioxidant, derivatives, deuterium dipalmitoylphosphatidylcholine, hydration, hydroquinones, longitudinal lyomesophase, parathion, peptides, proteins quadrupole quinones, relaxation respiration, simulations, splitting, time, tumor-cell},
pubstate = {published},
tppubtype = {article}
}