Enzymatic bioreduction of nitro groups plays an important role on the activity of biologically active nitroaromatic compounds. Electrochemical methods are useful tools to simulate in vivo metabolic processes. This work presents electrochemical studies, in protic media (EtOH+ phosphate buffer 4:6), using cyclic voltammetry (CV) of twelve Morita-Baylis-Hillman adducts (MBHA) with significant leishmanicidal activity. To facilitate the analysis, the molecules were grouped in four classes according to their side chains. Cyclic voltammograms display, in all cases, only one cathodic wave related to the formation of the correspondent hydroxylamines, which suffer further oxidation generating the nitroso derivatives in a sequential cycle. Ortho compounds exhibit more negative reduction potentials compared to the other isomers, in the same chemical class. This phenomenon could be related not only to structural effects but also to the presence of solvation spheres during the electroreduction process and/or stabilization of the resulting hydroxylamine. A proposal to explain the higher leishmanicidal activity of the ortho compounds compared with the meta and para compounds was suggested based on theoretical calculations (HF/6-31 + G */PCM, water, as a calculation level) that indicated lower thermodynamic stability for the ortho, in comparison to the corresponding meta and para hydroxylamines, fact that may suggest the easier transformation of the electrogenerated compounds into reactive electrophilic intermediates or final products, able to react with physiological important endobiotics. (C) 2014 Elsevier Ltd. All rights reserved.