%0 Journal Article %1 RN425 %A Aguilera-Venegas, B. %A Olea-Azar, C. %A Aran, V.J. %A Maya, J.D. %A Kemmerling, U. %A Speisky, H. %A Mendizabal, F. %D 2012 %J International Journal of Electrochemical Science %K 5-nitroindazole activity, antiprotozoal biological bisnitroindazoles, carbonyl chagas-disease control, density-functional derivatives, dqcauchile electron-spin-resonance, evaluation, free metabolism microsomal oxidative production, radical, reductase, reduction, ros spin stress, theory, thiol trapping, trypanosoma-cruzi, trypanothione %N 7 %P 5837-5863 %T Electrochemical, Esr and Theoretical Insights into the Free Radical Generation by 1,1 '-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds %U /brokenurl#<Go to ISI>://WOS:000306399700009 %V 7 %X 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.

@article{RN425, 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.}, added-at = {2019-12-04T03:57:35.000+0100}, author = {Aguilera-Venegas, B. and Olea-Azar, C. and Aran, V.J. and Maya, J.D. and Kemmerling, U. and Speisky, H. and Mendizabal, F.}, biburl = {https://www.bibsonomy.org/bibtex/203d00edf8d40b65ea0d79157508c3240/dqcauchile}, interhash = {07f56996d66d7c3a9a86b8f60172fa33}, intrahash = {03d00edf8d40b65ea0d79157508c3240}, issn = {1452-3981}, journal = {International Journal of Electrochemical Science}, keywords = {5-nitroindazole activity, antiprotozoal biological bisnitroindazoles, carbonyl chagas-disease control, density-functional derivatives, dqcauchile electron-spin-resonance, evaluation, free metabolism microsomal oxidative production, radical, reductase, reduction, ros spin stress, theory, thiol trapping, trypanosoma-cruzi, trypanothione}, number = 7, pages = {5837-5863}, timestamp = {2019-12-04T03:58:17.000+0100}, title = {Electrochemical, Esr and Theoretical Insights into the Free Radical Generation by 1,1 '-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds}, type = {Journal Article}, url = {/brokenurl#<Go to ISI>://WOS:000306399700009}, volume = 7, year = 2012 }