RT Journal Article
T1 Tetradentate polyamines as efficient metallodrugs for Chagas disease treatment in murine model.
A1 Olmo, Francisco
A1 Costas, Miquel
A1 Marin, Clotilde
A1 Rosales, Maria Jose
A1 Martin-Escolano, Ruben
A1 Cusso, Olaf
A1 Gutierrez-Sanchez, Ramon
A1 Ribas, Xavi
A1 Sanchez-Moreno, Manuel
K1 American trypanosomiasis
K1 Chemotherapy
K1 Murine model
K1 Tetradentate polyamines
AB A series of tetraamine-based compounds was prepared, and their trypanocidal effects against Trypanosoma cruzi and cytotoxicity were determined through the determination of IC50 values. In vivo assays were performed in mice, where parasitaemia levels were quantified by fresh blood examination and the assignment of a cure was determined by polymerase chain reaction and reactivation of blood parasitaemia levels after immunosuppression. The mechanisms of action were elucidated at metabolic and ultra-structural levels, by 1H NMR, Fe-SOD inhibition and TEM studies. The high-selectivity indexes observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. Compound 6 induced a remarkable decrease in the reactivation of parasitaemia after immunosuppression and curative rates of 33%. The experiments allowed us to select compound 6 as a promising candidate for treating Chagas disease, but a further high-level study should be considered to obtain an improved efficiency.
PB Taylor & Francis
YR 2016
FD 2016-06-02
LK http://hdl.handle.net/10668/10143
UL http://hdl.handle.net/10668/10143
LA en
NO Olmo F, Costas M, Marín C, Rosales MJ, Martín-Escolano R, Cussó O, et al. Tetradentate polyamines as efficient metallodrugs for Chagas disease treatment in murine model. J Chemother. 2017 Apr;29(2):83-93.
NO We acknowledge Generalitat de Catalunya for an ICREA Academia Award (X.R. and M.C.). Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO), CONSOLIDER-INGENIO 2010 CSD2010-00065. F.O. is grateful for a FPU Grant (AP2010-3562) from the Ministry of Education of Spain.
DS RISalud
RD Apr 19, 2025