2015 |
Mena, N P; Garcia-Beltran, O; Lourido, F; Urrutia, P J; Mena, R; Castro-Castillo, V; Cassels, B K; Nunez, M The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death Artículo de revista Biochemical and Biophysical Research Communications, 463 (4), pp. 787-792, 2015, ISSN: 0006-291x. Resumen | Enlaces | BibTeX | Etiquetas: brain chelation, contributes, degeneration, disease, diseases, homeostasis, hydroxyquinolines, in-vivo, inhibition iron iron, mitochondria, neurodegenerative parkinson's parkinsons-disease, substantia-nigra @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} } 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. |
2013 |
Soto-Delgado, J; Bahamonde-Padilla, V E; Araya-Maturana, R; Weiss-Lopez, B On the Mechanism of Biological Activity of Hydroquinone Derivatives That Inhibit Tumor Cell Respiration. A Theoretical Study Artículo de revista Computational and Theoretical Chemistry, 1013 , pp. 97-101, 2013, ISSN: 2210-271x. Resumen | Enlaces | BibTeX | Etiquetas: alpha-tocopheryl antioxidant, antitumoral calculation, cancer, cell dft drugs, generation, growth, hydroquinone, in-vivo, mechanism, mitochondria, oxidation, pathways respiration, semiquinone, succinate, targeting tumor @article{RN157, title = {On the Mechanism of Biological Activity of Hydroquinone Derivatives That Inhibit Tumor Cell Respiration. A Theoretical Study}, author = { J. Soto-Delgado and V.E. Bahamonde-Padilla and R. Araya-Maturana and B. Weiss-Lopez}, url = {/brokenurl#<Go to ISI>://WOS:000319102800015}, doi = {10.1016/j.comptc.2013.03.007}, issn = {2210-271x}, year = {2013}, date = {2013-01-01}, journal = {Computational and Theoretical Chemistry}, volume = {1013}, pages = {97-101}, publisher = {2013 Elsevier B.V.}, abstract = {A simple mechanism to understand the biological activity of a series of hydroquinone derivatives is proposed. To validate this proposition Gibbs free energies of formation of the different species involved were calculated. The calculations were performed using density functional theory (DFT) at B3LYP/6-31++G(2df,p) level of theory, including solvation effect. The results show that two important variables to examine are the equilibrium phenol-phenoxide and the solvation energy of neutral species, since the balance between both variables affects the capability of the molecules to cross membranes. Once the molecule crossed the membrane, the formation of radical species shows a qualitative correlation with the magnitude of IC50 values. This provides a reasonable criterion to search for more efficient anticancer drug.}, keywords = {alpha-tocopheryl antioxidant, antitumoral calculation, cancer, cell dft drugs, generation, growth, hydroquinone, in-vivo, mechanism, mitochondria, oxidation, pathways respiration, semiquinone, succinate, targeting tumor}, pubstate = {published}, tppubtype = {article} } A simple mechanism to understand the biological activity of a series of hydroquinone derivatives is proposed. To validate this proposition Gibbs free energies of formation of the different species involved were calculated. The calculations were performed using density functional theory (DFT) at B3LYP/6-31++G(2df,p) level of theory, including solvation effect. The results show that two important variables to examine are the equilibrium phenol-phenoxide and the solvation energy of neutral species, since the balance between both variables affects the capability of the molecules to cross membranes. Once the molecule crossed the membrane, the formation of radical species shows a qualitative correlation with the magnitude of IC50 values. This provides a reasonable criterion to search for more efficient anticancer drug. |
2015 |
The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death Artículo de revista Biochemical and Biophysical Research Communications, 463 (4), pp. 787-792, 2015, ISSN: 0006-291x. |
2013 |
On the Mechanism of Biological Activity of Hydroquinone Derivatives That Inhibit Tumor Cell Respiration. A Theoretical Study Artículo de revista Computational and Theoretical Chemistry, 1013 , pp. 97-101, 2013, ISSN: 2210-271x. |