2016 |
Cornejo, A; Salgado, F; Caballero, J; Vargas, R; Simirgiotis, M; Areche, C Secondary Metabolites in Ramalina Terebrata Detected by Uhplc/Esi/Ms/Ms and Identification of Parietin as Tau Protein Inhibitor Artículo de revista International Journal of Molecular Sciences, 17 (8), 2016, ISSN: 1422-0067. Resumen | Enlaces | BibTeX | Etiquetas: alzheimer's alzheimers-disease, biological disease, docking, evaluation, fibril filaments, formation helical lichen lichens, liquid-chromatography, mass-spectrometry, molecular paired parietin, phenolic-compounds, protein, ramalina, tau uhplc-q/orbitrap/ms/ms, uhplc/ms, xanthoria-parietina @article{RN286, title = {Secondary Metabolites in Ramalina Terebrata Detected by Uhplc/Esi/Ms/Ms and Identification of Parietin as Tau Protein Inhibitor}, author = { A. Cornejo and F. Salgado and J. Caballero and R. Vargas and M. Simirgiotis and C. Areche}, url = {/brokenurl#<Go to ISI>://WOS:000382337900115}, doi = {10.3390/ijms17081303}, issn = {1422-0067}, year = {2016}, date = {2016-01-01}, journal = {International Journal of Molecular Sciences}, volume = {17}, number = {8}, abstract = {Liquid chromatography coupled with mass spectrometry is an outstanding methodology for fast analysis of phenolic compounds in biological samples. Twenty two compounds were quickly and accurately identified in the methanolic extract of the Antarctic lichen Ramalina terebrata for the first time using ultra high pressure liquid chromatography coupled with photodiode array detector and high resolution mass spectrometry (UHPLC-PDA-Q/Orbitrap/MS/MS). In addition, the extract and the four compounds isolated from this species were tested for the inhibitory activity of tau protein aggregation, which is a protein involved in Alzheimer's disease (AD). All compounds showed null activity with the exception of parietin, which it was able to inhibit aggregation process of tau in a concentration range between 3 mu g/mL (10 mu M) to 28 mu g/mL (100 mu M). In addition, we show how parietin interact with tau (306)VQIVYK(311) hexapeptide inside of the microtubule binding domain (4R) with the help of molecular docking experiments. Finally, the constituents present in the methanolic extract could possibly contribute to the established anti-aggregation activity for this extract and this in-depth analysis of the chemical composition of R. terebrata could guide further research into its medicinal properties and potential uses.}, keywords = {alzheimer's alzheimers-disease, biological disease, docking, evaluation, fibril filaments, formation helical lichen lichens, liquid-chromatography, mass-spectrometry, molecular paired parietin, phenolic-compounds, protein, ramalina, tau uhplc-q/orbitrap/ms/ms, uhplc/ms, xanthoria-parietina}, pubstate = {published}, tppubtype = {article} } Liquid chromatography coupled with mass spectrometry is an outstanding methodology for fast analysis of phenolic compounds in biological samples. Twenty two compounds were quickly and accurately identified in the methanolic extract of the Antarctic lichen Ramalina terebrata for the first time using ultra high pressure liquid chromatography coupled with photodiode array detector and high resolution mass spectrometry (UHPLC-PDA-Q/Orbitrap/MS/MS). In addition, the extract and the four compounds isolated from this species were tested for the inhibitory activity of tau protein aggregation, which is a protein involved in Alzheimer's disease (AD). All compounds showed null activity with the exception of parietin, which it was able to inhibit aggregation process of tau in a concentration range between 3 mu g/mL (10 mu M) to 28 mu g/mL (100 mu M). In addition, we show how parietin interact with tau (306)VQIVYK(311) hexapeptide inside of the microtubule binding domain (4R) with the help of molecular docking experiments. Finally, the constituents present in the methanolic extract could possibly contribute to the established anti-aggregation activity for this extract and this in-depth analysis of the chemical composition of R. terebrata could guide further research into its medicinal properties and potential uses. |
2015 |
Aguirre, P; Mena, N P; Carrasco, C M; Munoz, Y; Perez-Henriquez, P; Morales, R A; Cassels, B K; Mendez-Galvez, C; Garcia-Beltran, O; González-Billault, C; Nunez, M Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons Artículo de revista Plos One, 10 (12), 2015, ISSN: 1932-6203. Resumen | Enlaces | BibTeX | Etiquetas: apoptosis, degeneration, dendritic disease, expression, induced models, neurodegeneration, protein, restoration substantia-nigra, tree @article{RN242, title = {Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons}, author = { P. Aguirre and N.P. Mena and C.M. Carrasco and Y. Munoz and P. Perez-Henriquez and R.A. Morales and B.K. Cassels and C. Mendez-Galvez and O. Garcia-Beltran and C. Gonz\'{a}lez-Billault and M. Nunez}, url = {/brokenurl#<Go to ISI>://WOS:000366715900118}, doi = {10.1371/journal.pone.0144848}, issn = {1932-6203}, year = {2015}, date = {2015-01-01}, journal = {Plos One}, volume = {10}, number = {12}, abstract = {Neuronal death in Parkinson's disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.}, keywords = {apoptosis, degeneration, dendritic disease, expression, induced models, neurodegeneration, protein, restoration substantia-nigra, tree}, pubstate = {published}, tppubtype = {article} } Neuronal death in Parkinson's disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death. |
Vera, A M; Carcamo, J J; Aliaga, A E; Gomez-Jeria, J S; Kogan, M J; Campos-Vallette, M Interaction of the Clpffd Peptide with Gold Nanospheres. A Raman, Surface Enhanced Raman Scattering and Theoretical Study Artículo de revista Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy, 134 , pp. 251-256, 2015, ISSN: 1386-1425. Resumen | Enlaces | BibTeX | Etiquetas: alzheimer-disease, anti-aggregation approximations, assemblies, beta-amyloid, calculations, clpffd extended hartree-fock htickel molecular-orbital nanoparticles, of peptide peptide, protein, sers, silver, spectroscopy, stability theories, theory type @article{RN262, title = {Interaction of the Clpffd Peptide with Gold Nanospheres. A Raman, Surface Enhanced Raman Scattering and Theoretical Study}, author = { A.M. Vera and J.J. Carcamo and A.E. Aliaga and J.S. Gomez-Jeria and M.J. Kogan and M. Campos-Vallette}, url = {/brokenurl#<Go to ISI>://WOS:000342718700034}, doi = {10.1016/j.saa.2014.06.116}, issn = {1386-1425}, year = {2015}, date = {2015-01-01}, journal = {Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy}, volume = {134}, pages = {251-256}, publisher = {2014 Elsevier B.V.}, abstract = {In a previous work we demonstrated that toxic aggregates of the protein beta-amyloid (ATA beta) involved in the Alzheimer's disease (AD) can be destabilized upon electromagnetic irradiation of the peptide Cys-Leu-Pro-Phe-Phe-Asp (CLPFFD) adsorbed on gold nanospheres (AuNSs). For a selective recognition of the therapeutic target (i.e. ATA beta) of AD by the conjugates peptide-nanoparticle it is relevant to understand how the interaction between attached ligands and nanoparticles occurs. In this work a surface enhanced Raman scattering spectroscopy (SERS) study of the interactions of CLPFFD with AuNSs of 10 nm average diameter was carried out. The SERS data suggest that phenylalanine displays its aromatic ring coplanar to the surface which is supported by theoretical data obtained from molecular mechanics (MM) and Extended Huckel Theory (EHT) calculations.}, keywords = {alzheimer-disease, anti-aggregation approximations, assemblies, beta-amyloid, calculations, clpffd extended hartree-fock htickel molecular-orbital nanoparticles, of peptide peptide, protein, sers, silver, spectroscopy, stability theories, theory type}, pubstate = {published}, tppubtype = {article} } In a previous work we demonstrated that toxic aggregates of the protein beta-amyloid (ATA beta) involved in the Alzheimer's disease (AD) can be destabilized upon electromagnetic irradiation of the peptide Cys-Leu-Pro-Phe-Phe-Asp (CLPFFD) adsorbed on gold nanospheres (AuNSs). For a selective recognition of the therapeutic target (i.e. ATA beta) of AD by the conjugates peptide-nanoparticle it is relevant to understand how the interaction between attached ligands and nanoparticles occurs. In this work a surface enhanced Raman scattering spectroscopy (SERS) study of the interactions of CLPFFD with AuNSs of 10 nm average diameter was carried out. The SERS data suggest that phenylalanine displays its aromatic ring coplanar to the surface which is supported by theoretical data obtained from molecular mechanics (MM) and Extended Huckel Theory (EHT) calculations. |
2013 |
Vega, De La A P; Alarcon, D A; Gomez-Jeria, J S Journal of the Chilean Chemical Society, 58 (4), pp. 2148-2157, 2013, ISSN: 0717-9707. Resumen | Enlaces | BibTeX | Etiquetas: antigenic binding, c chemistry, core crystal-structure, dependent derivatives, discovery, hcv hepatitis ns5b nucleoside nucleotide, pharmacology, polymerase, protein, qsar, quantum replicons, rna-polymerase, site, structure-affinity, virus @article{RN169, title = {Quantum Chemical Study of the Relationships between Electronic Structure and Pharmacokinetic Profile, Inhibitory Strength toward Hepatitis C Virus Ns5b Polymerase and Hcv Replicons of Indole-Based Compounds}, author = { A.P. De La Vega and D.A. Alarcon and J.S. Gomez-Jeria}, url = {/brokenurl#<Go to ISI>://WOS:000331238800051}, doi = {10.4067/S0717-97072013000400055}, issn = {0717-9707}, year = {2013}, date = {2013-01-01}, journal = {Journal of the Chilean Chemical Society}, volume = {58}, number = {4}, pages = {2148-2157}, abstract = {This paper uses newly developed and extended quantum chemical methods in an attempt to advance the knowledge of the relationship between the variation of several local atomic descriptors of the electronic structure and the variation of the inhibitory capacity of a group of reversible and irreversible inhibitors of hepatitis C virus NS5B polymerase. Good structure-activity relationships were obtained for both kinds of compounds. Some processes are charge-, orbital- and/or steric-controlled. The action mechanisms seem to be different for reversible and irreversible inhibitors. Also, good QSAR equations were obtained for the activities of these compounds in a cellular replicon assay and for pharmacokinetic profiles. The local atomic hardness seems to give a good account of the interaction of the drugs with apolar sites of the partner (enzyme, receptor, etc.). This is the first time that a purely quantum-chemical index is able to deal directly with this kind of interaction.}, keywords = {antigenic binding, c chemistry, core crystal-structure, dependent derivatives, discovery, hcv hepatitis ns5b nucleoside nucleotide, pharmacology, polymerase, protein, qsar, quantum replicons, rna-polymerase, site, structure-affinity, virus}, pubstate = {published}, tppubtype = {article} } This paper uses newly developed and extended quantum chemical methods in an attempt to advance the knowledge of the relationship between the variation of several local atomic descriptors of the electronic structure and the variation of the inhibitory capacity of a group of reversible and irreversible inhibitors of hepatitis C virus NS5B polymerase. Good structure-activity relationships were obtained for both kinds of compounds. Some processes are charge-, orbital- and/or steric-controlled. The action mechanisms seem to be different for reversible and irreversible inhibitors. Also, good QSAR equations were obtained for the activities of these compounds in a cellular replicon assay and for pharmacokinetic profiles. The local atomic hardness seems to give a good account of the interaction of the drugs with apolar sites of the partner (enzyme, receptor, etc.). This is the first time that a purely quantum-chemical index is able to deal directly with this kind of interaction. |
2016 |
Secondary Metabolites in Ramalina Terebrata Detected by Uhplc/Esi/Ms/Ms and Identification of Parietin as Tau Protein Inhibitor Artículo de revista International Journal of Molecular Sciences, 17 (8), 2016, ISSN: 1422-0067. |
2015 |
Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons Artículo de revista Plos One, 10 (12), 2015, ISSN: 1932-6203. |
Interaction of the Clpffd Peptide with Gold Nanospheres. A Raman, Surface Enhanced Raman Scattering and Theoretical Study Artículo de revista Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy, 134 , pp. 251-256, 2015, ISSN: 1386-1425. |
2013 |
Journal of the Chilean Chemical Society, 58 (4), pp. 2148-2157, 2013, ISSN: 0717-9707. |