Trypanocidal activity of thioamide-substituted imidazoquinolinone: electrochemical properties and biological effects.
Three thioamide-substituted imidazoquinolinone, which possess a heterocyclic center similar to tryptanthrin and are named C1, C2, and C3, were studied regarding (a) their in vitro anti-Trypanosoma cruzi activity, (b) their cytotoxicity and electrochemical behaviour, and (c) their effect on cell viability, redox state, and mitochondrial function. The assayed compounds showed a significant activity against the proliferative forms, but only C1 showed activity on the trypomastigote form (for C1, IC50  epi = 1.49 μM; IC50  amas = 1.74 μM; and IC50  try = 34.89 μM). The presence of an antioxidant compound such as ascorbic acid or dithiotreitol induced a threefold increase in the antiparasitic activity, whereas glutathione had a dual effect depending on its concentration. Our results indicate that these compounds, which exhibited low toxicity to the host cells, can be reduced inside the parasite by means of the pool of low molecular weight thiols, causing oxidative stress and parasite death by apoptosis. The antiparasitic activity of the compounds studied could be explained by a loss of the capacity of the antioxidant defense system of the parasite to keep its intracellular redox state. C1 could be considered a good candidate for in vivo evaluation.
Departamento de Microbiología, Facultad de Medicina, IMPaM (UBA-CONICET) and Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, UBA, Paraguay 2155 P13, 1121 Buenos Aires, Argentina.
Fernanda M
FM
Frank
Alejandra B
AB
Ciccarelli
Mariela
M
Bollini
Ana M
AM
Bruno
Alcira
A
Batlle
Maria E
ME
Lombardo