2012 |
Aguilera-Venegas, B; Olea-Azar, C; Aran, V J; Maya, J D; Kemmerling, U; Speisky, H; Mendizabal, F Electrochemical, Esr and Theoretical Insights into the Free Radical Generation by 1,1 '-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds Artículo de revista International Journal of Electrochemical Science, 7 (7), pp. 5837-5863, 2012, ISSN: 1452-3981. Resumen | Enlaces | BibTeX | Etiquetas: antiprotozoal biological bisnitroindazoles, carbonyl chagas-disease control, density-functional derivatives, electron-spin-resonance, evaluation, free metabolism microsomal oxidative production, radical, reductase, reduction, ros spin stress, theory, thiol trapping, trypanosoma-cruzi, trypanothione @article{RN425, title = {Electrochemical, Esr and Theoretical Insights into the Free Radical Generation by 1,1 '-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds}, author = { B. Aguilera-Venegas and C. Olea-Azar and V.J. Aran and J.D. Maya and U. Kemmerling and H. Speisky and F. Mendizabal}, url = {/brokenurl#<Go to ISI>://WOS:000306399700009}, issn = {1452-3981}, year = {2012}, date = {2012-01-01}, journal = {International Journal of Electrochemical Science}, volume = {7}, number = {7}, pages = {5837-5863}, abstract = {A comprehensive multidisciplinary study is conducted here in order to assess the electrochemical behavior of a series of 1,1'-hydrocarbylenebisindazoles derivatives and its potential use as anti-T.cruzi drugs. At first, we have determined the electrochemical reduction mechanisms of this family by cyclic voltammetry (CV) studies, from which three kind of reduction mechanisms -depending on the substituent at positions 3 and 3'-were established, but sharing a first common step corresponding to the generation of a nitro anion radical, which was corroborated by ESR spectroscopy, showing a comparable hyperfine splitting pattern and a strong influence on the ESR spectral linewidths due to the radical-solvent interactions. Furthermore, in order to give a rational description about the electrochemical and ESR results, open- and closed-shell structures of bisindasoles were subjected to theoretical estimations at different levels of theory. For open-shell structures, the hyperfine splitting patterns were confirmed while for the closed-shell systems case, clear evidence about the electrochemical reactivity -in terms of their frontiers orbitals-were obtained. To conclude, all these compounds were assayed as growth inhibitors against T. cruzi, from which some degree of activity was observed for this family, highlighting a compound almost as active as the reference drug. Finally, in order to get some information about the potential action mechanisms involved in the trypanocidal activity, molecular modeling and spin trapping studies were also done.}, keywords = {antiprotozoal biological bisnitroindazoles, carbonyl chagas-disease control, density-functional derivatives, electron-spin-resonance, evaluation, free metabolism microsomal oxidative production, radical, reductase, reduction, ros spin stress, theory, thiol trapping, trypanosoma-cruzi, trypanothione}, pubstate = {published}, tppubtype = {article} } A comprehensive multidisciplinary study is conducted here in order to assess the electrochemical behavior of a series of 1,1'-hydrocarbylenebisindazoles derivatives and its potential use as anti-T.cruzi drugs. At first, we have determined the electrochemical reduction mechanisms of this family by cyclic voltammetry (CV) studies, from which three kind of reduction mechanisms -depending on the substituent at positions 3 and 3'-were established, but sharing a first common step corresponding to the generation of a nitro anion radical, which was corroborated by ESR spectroscopy, showing a comparable hyperfine splitting pattern and a strong influence on the ESR spectral linewidths due to the radical-solvent interactions. Furthermore, in order to give a rational description about the electrochemical and ESR results, open- and closed-shell structures of bisindasoles were subjected to theoretical estimations at different levels of theory. For open-shell structures, the hyperfine splitting patterns were confirmed while for the closed-shell systems case, clear evidence about the electrochemical reactivity -in terms of their frontiers orbitals-were obtained. To conclude, all these compounds were assayed as growth inhibitors against T. cruzi, from which some degree of activity was observed for this family, highlighting a compound almost as active as the reference drug. Finally, in order to get some information about the potential action mechanisms involved in the trypanocidal activity, molecular modeling and spin trapping studies were also done. |
2011 |
Aguilera-Venegas, B; Olea-Azar, C; Norambuena, E; Aran, V J; Mendizabal, F; Lapier, M; Maya, J D; Kemmerling, U; Lopez-Munoz, R Esr, Electrochemical, Molecular Modeling and Biological Evaluation of 4-Substituted and 1,4-Disubstituted 7-Nitroquinoxalin-2-Ones as Potential Anti-Trypanosoma Cruzi Agents Artículo de revista Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy, 78 (3), pp. 1004-1012, 2011, ISSN: 1386-1425. Resumen | Enlaces | BibTeX | Etiquetas: 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 @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} } 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. |
2012 |
Electrochemical, Esr and Theoretical Insights into the Free Radical Generation by 1,1 '-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds Artículo de revista International Journal of Electrochemical Science, 7 (7), pp. 5837-5863, 2012, ISSN: 1452-3981. |
2011 |
Esr, Electrochemical, Molecular Modeling and Biological Evaluation of 4-Substituted and 1,4-Disubstituted 7-Nitroquinoxalin-2-Ones as Potential Anti-Trypanosoma Cruzi Agents Artículo de revista Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy, 78 (3), pp. 1004-1012, 2011, ISSN: 1386-1425. |