In vitro and in vivo trypanosomicidal activity of pyrazole-containing macrocyclic and macrobicyclic polyamines: their action on acute and chronic phases of Chagas disease.


Sánchez-Moreno, M; Marín, C; Navarro, P; Lamarque, L; García-España, E; Miranda, C; Huertas, O; Olmo, F; Gómez-Contreras, F; Pitarch, J; Arrebola, F; (2012) In vitro and in vivo trypanosomicidal activity of pyrazole-containing macrocyclic and macrobicyclic polyamines: their action on acute and chronic phases of Chagas disease. Journal of medicinal chemistry, 55 (9). pp. 4231-43. ISSN 0022-2623 DOI: https://doi.org/10.1021/jm2017144

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Abstract

The in vitro and in vivo anti- Trypanosoma cruzi activity of the pyrazole-containing macrobicyclic polyamine 1 and N-methyl- and N-benzyl-substituted monocyclic polyamines 2 and 3 was studied. Activity against both the acute and chronic phases of Chagas disease was considered. The compounds were more active against the parasite and less toxic against Vero cells than the reference drug benznidazole, but 1 and 2 were especially effective, where cryptand 1 was the most active, particularly in the chronic phase. The activity results found for these compounds were complemented and discussed by considering their inhibitory effect on the iron superoxide dismutase enzyme of the parasite, the nature of the metabolites excreted after treatment, and the ultrastructural alterations produced. A complementary histopathological analysis confirmed that the compounds tested were significantly less toxic to mammals than the reference drug and that 1 and 2 exhibited lower levels of damage than 3.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Neglected Tropical Diseases Network
PubMed ID: 22443115
Web of Science ID: 303785900015
URI: http://researchonline.lshtm.ac.uk/id/eprint/2920723

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