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 viab...
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todo:paper_1741427X_v2013_n_p_Frank2023-10-03T16:30:16Z Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects Frank, F.M. Ciccarelli, A.B. Bollini, M. Bruno, A.M. Batlle, A. Lombardo, M.E. antiparasitic agent imidazoquinolinone derivative thioamide unclassified drug animal cell antitrypanosomal activity apoptosis article biological activity cell viability controlled study cytotoxicity cytotoxicity test drug activity electrochemical analysis epimastigote IC 50 in vitro study male molecular weight mouse nonhuman oxidation reduction state oxidative stress priority journal Trypanosoma cruzi trypomastigote 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 M; IC50 amas=1.74 M; and IC50 try=34.89 M). 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. © 2013 Fernanda M. Frank et al. Fil:Ciccarelli, A.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lombardo, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1741427X_v2013_n_p_Frank |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
antiparasitic agent imidazoquinolinone derivative thioamide unclassified drug animal cell antitrypanosomal activity apoptosis article biological activity cell viability controlled study cytotoxicity cytotoxicity test drug activity electrochemical analysis epimastigote IC 50 in vitro study male molecular weight mouse nonhuman oxidation reduction state oxidative stress priority journal Trypanosoma cruzi trypomastigote |
| spellingShingle |
antiparasitic agent imidazoquinolinone derivative thioamide unclassified drug animal cell antitrypanosomal activity apoptosis article biological activity cell viability controlled study cytotoxicity cytotoxicity test drug activity electrochemical analysis epimastigote IC 50 in vitro study male molecular weight mouse nonhuman oxidation reduction state oxidative stress priority journal Trypanosoma cruzi trypomastigote Frank, F.M. Ciccarelli, A.B. Bollini, M. Bruno, A.M. Batlle, A. Lombardo, M.E. Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects |
| topic_facet |
antiparasitic agent imidazoquinolinone derivative thioamide unclassified drug animal cell antitrypanosomal activity apoptosis article biological activity cell viability controlled study cytotoxicity cytotoxicity test drug activity electrochemical analysis epimastigote IC 50 in vitro study male molecular weight mouse nonhuman oxidation reduction state oxidative stress priority journal Trypanosoma cruzi trypomastigote |
| description |
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 M; IC50 amas=1.74 M; and IC50 try=34.89 M). 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. © 2013 Fernanda M. Frank et al. |
| format |
JOUR |
| author |
Frank, F.M. Ciccarelli, A.B. Bollini, M. Bruno, A.M. Batlle, A. Lombardo, M.E. |
| author_facet |
Frank, F.M. Ciccarelli, A.B. Bollini, M. Bruno, A.M. Batlle, A. Lombardo, M.E. |
| author_sort |
Frank, F.M. |
| title |
Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects |
| title_short |
Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects |
| title_full |
Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects |
| title_fullStr |
Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects |
| title_full_unstemmed |
Trypanocidal activity of thioamide-substituted imidazoquinolinone: Electrochemical properties and biological effects |
| title_sort |
trypanocidal activity of thioamide-substituted imidazoquinolinone: electrochemical properties and biological effects |
| url |
http://hdl.handle.net/20.500.12110/paper_1741427X_v2013_n_p_Frank |
| work_keys_str_mv |
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