RT Journal Article
T1 An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.
A1 Olmo, Francisco
A1 Urbanová, Kristína
A1 Rosales, Maria Jose
A1 Martín-Escolano, Ruben
A1 Sánchez-Moreno, Manuel
A1 Marín, Clotilde
K1 Anti-chagasic
K1 Chemotherapy
K1 Trypanosomiasis
K1 Hydroxyphthalazine derivatives
K1 Antiparasitarios
K1 Enfermedad de chagas
K1 Citometría de flujo
K1 Concentración 50 inhibidora
K1 Imagen por resonancia magnética
K1 Ratones consanguíneos BALB C
K1 Microscopía
K1 Parásitos
K1 Células vero
AB In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.
PB Elsevier
YR 2015
FD 2015-06-20
LK http://hdl.handle.net/10668/2129
UL http://hdl.handle.net/10668/2129
LA en
NO Olmo F, Urbanová K, Rosales MJ, Martín-Escolano R, Sánchez-Moreno M, Marín C. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase. Int J Parasitol Drugs Drug Resist. 2015                         ; 5(3):110-6
NO Journal Article;
DS RISalud
RD Apr 14, 2025