Trypanocidal activity of thioamide-substituted imidazoisoquinolinones: Electrochemical properties and biological effects

FRANK FM; CICCARELLI AB; BOLLINI M; BRUNO AM; BATLLE A; LOMBARDO ME

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2013 vol. 2013 p. 1 - 8

1741-427X

Three thioamide-sustituted imidazoisoquinolinones, named C1, C2 and C3, were studied regarding : a) its in vitro anti-T. cruzi activity against the three stages of Trypanosoma cruzi, b) its cytotoxicity and electrochemical behaviour and c) its effect on cell viability and the redox state and mitochondrial function . The assayed compounds showed a significant activity against the epimastigote and amastigote 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 three-fold increase in the antiparasitic activity of these compounds, whereas glutathione had a dual effect, inducing an increase or an inhibition of the activity, depending on its concentration. Based on their electrophilic properties these compounds can be reduced inside the parasite by means of the pool of low molecular weight thiols. The antiparasitic activity of the compounds studied could be explained by a loss of capacity of the antioxidant defense system to keep the cell redox state and/or by a damage of the mitochondria, leading to cell death by apoptosis. Therefore, C1 could be considered a good candidate to be tested in vivo in an animal model of Chagas? disease.