Avaliação antioxidante e investigação bioeletroquímica de Nitronas e derivados

Abstract

Nitrones are known for their ability to capture radicals and consequently reduce, in case of reactive oxygen species (ROS, the oxidative stress, making them promising synthetic antioxidants with high therapeutic potential. They are being studied for the treatment of various pathologies, such as cancer, stroke, Parkinson's and Alzheimer's diseases, including neglected tropical diseases. Since the molecular mechanism of biological action of this group of compounds is not yet fully elucidated, the present work investigated the electrochemical, spectroelectrochemical and spectrophotometric behavior of synthetic nitrones, derivatives and precursors. In addition, their antioxidant capacity was evaluated by the spectroscopic methods FRAP and antioxidant capacity against the DPPH• radical (2-2-diphenyl-1-picryl-hydralazine) (%RSA). Cyclic (CVs) and differential pulse (DPVs) voltammograms on a glassy carbon electrode (GCE) were recorded in an aprotic medium (acetonitrile + 0.1 M TBAPF6) in order to mimic the lipophilic biological environments and obtain data on the mechanism of reduction, oxidation, analysis of electrogenerated intermediates, in the perspective of contributing to the elucidation of their molecular mechanisms of biological action. The p-nitrobenzaldehyde and 5-nitro-2-furaldehyde standards were studied electrochemically under the same conditions. All compounds studied showed to be electrochemically active in the cathodic region of the voltammograms. The LQB-109 and LQB-123 nitrones showed similar behavior, with irreversible reduction waves and a potential more negative than -2.0 V, relative to the nitrone reduction. As for the compounds LQB-569, LQB-303, LQB-484, LQB-304 and LQB-534 that have double redox function, that is, nitrone and nitro groups, reduction peaks characteristic of both were observed. When compared to the standards (compounds that have only the nitrone group or only the nitro group), it is noted that the nitroaromatic group is reduced first in a quase reversible monoelectronic transfer. The spectroelectrochemical investigation for the nitronitrone LQB-303 revealed a decrease in the absorbance of some absorption bands and the appearance of new ones, during the application of cathodic potentials, which suggest the reduction of the nitronitrone and formation of its reduction products. In the investigation of the antioxidant capacity, the values %RSA for the DPPH• radical ranged from 10.14 - 37.25% inhibition, while the FRAP values ranged from 126.86 - 196, 84 mg trolox equivalent (TE)/mol of compound. In the analysis of the optical properties of these compounds using UV-Vis spectroscopy, all compounds showed absorption bands in the UV-Vis region, between 190 - 900 nm. In order to evaluate the reactivity and verify the electron donating function of nitrones, the interaction between LQB-109 and DDQ quinone (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) was investigated. The appearance of new bands in the region 400 – 600 nm suggests the formation of a charge transfer complex. Electro- and spectrochemical methods proved to be adequate in the redox study of nitrones, derivatives and precursors and were correlated with leishmanicidal activities, mainly for the more electrophilic nitronitrones LQB 303 and LQB-484, which were significantly leishmanicidal, with low toxicity.