Potent 5-nitrofuran derivatives inhibitors of Trypanosoma cruzi growth: electrochemical, spectroscopic and biological studies

Abstract

Cyclic voltammetry and electron spin resonance techniques were used in the investigation of several potential antiprotozoal containing thiosemicarbazone and carbamate nitrofurans. In the electrochemical behaviour, a self-protonation process involving the nitro group was observed. The reactivity of the nitro anion radical for these derivatives with glutathione, a biological relevant thiol, was also studied in means of cyclic voltammetry. These studies demonstrated that glutathione could react with radical species from 5-nitrofuryl system. Furthermore, from the voltammetric results, some parameters of biological significance as E(7)(1) (indicative of the biological nitro anion radical formation), and [Formula: see text] (thermodynamic indicator the of oxygen redox cycling) have been calculated. We also evaluated the stability of the nitro anion radical in terms of the dimerization constant (k(d)). The nitrofuran-free radicals from cyclic voltammetry were characterized by electron spin resonance. A clear dependence between both the thiosemicarbazone or carbamate substructure and the length of the linker, furyl- or furylpropenyl-spacer, and the delocalization of the unpaired electron was observed. Through of biological assays we obtained important parameters that account for the selective anti-trypanosomal activity of these derivatives. The trypomastigote viability study showed that all derivatives are as active as in the epimastigote form of the parasite in a doses dependent manner.