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

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 E71 (indicative of the biological nitro anion radical formation), and KO2KO2 (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 (kd). 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.

Graphical abstractCyclic voltammetry and electron spin resonance techniques were used in the investigation of several potential antiprotozoal containing thiosemicarbazone and carbamatenitrofurans. 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 E71 (indicative of the biological nitro anion radical formation), and KO2KO2. The nitrofuran-free radicals from cyclic voltammetry were characterized by electron spin resonance. The trypomastigote viability study showed that all derivatives are as active as in the epimastigote form of the parasite in a doses dependent manner.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Cyclic voltammetry and electron spin resonance techniques were used in the investigation of several potential antiprotozoal containing thiosemicarbazone and carbamatenitrofurans. ► These studies demonstrated that glutathione could react with radical species from 5-nitrofuryl system. ► The trypomastigote viability study showed that all derivatives are as active as in the epimastigote form of the parasite in a doses dependent manner.