title: 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.
authors.affiliation: Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Quimicas y Famacéuticas, Universidad de Chile, Olivos 1007, Independencia, Santiago, Chile.
authors.forename: C Maria
authors.initials: CM
authors.lastname: Aravena
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Olea
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodríguez-Becerra
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D014355:Chagas Disease / Q000188:drug therapy; D055664:Electrochemical Techniques; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D051379:Mice; D009581:Nitrofurans / Q000737:chemistry* / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000981:Antiprotozoal Agents; D009581:Nitrofurans; D013882:Thiosemicarbazones; D005978:Glutathione