Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30711
Title: Biological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi
Authors: Batista, D. G. J.
Pacheco, M. G. O.
Kumar, A.
Branowska, D.
Ismail, M. A.
Hu, L.
Boykin, D. W.
Soeiro, Maria Nazaré C.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Georgia State University. Department of Chemistry. Atlanta, Georgia, USA.
Georgia State University. Department of Chemistry. Atlanta, Georgia, USA.
Georgia State University. Department of Chemistry. Atlanta, Georgia, USA.
Georgia State University. Department of Chemistry. Atlanta, Georgia, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Abstract: No vaccines or safe chemotherapy are available for Chagas disease. Pentamidine and related di-cations are DNA minor groove-binders with broad-spectrum anti-protozoal activity. Therefore our aim was to evaluate the in vitro efficacy of di-cationic compounds - DB1645, DB1582, DB1651, DB1646, DB1670 and DB1627 - against bloodstream trypomastigotes (BT) and intracellular forms of Trypanosoma cruzi. Cellular targets of these compounds in treated parasites were also analysed by fluorescence and transmission electron microscopy (TEM). DB1645, DB1582 and DB1651 were the most active against BT showing IC50 values ranging between 0.15 and 6.9 microm. All compounds displayed low toxicity towards mammalian cells and DB1645, DB1582 and DB1651 were also the most effective against intracellular parasites, with IC50 values ranging between 7.3 and 13.3 microm. All compounds localized in parasite nuclei and kDNA (with greater intensity in the latter structure), and DB1582 and DB1651 also concentrated in non-DNA-containing cytoplasmic organelles possibly acidocalcisomes. TEM revealed alterations in mitochondria and kinetoplasts, as well as important disorganization of microtubules. Our data provide further information regarding the activity of this class of compounds upon T. cruzi which should aid future design and synthesis of agents that could be used for Chagas disease therapy.
Keywords: Trypanosoma cruzi
Chagas Disease
chemotherapy
aromatic diamidines
keywords: Trypanosoma cruzi
Doença de Chagas
Quimioterapia
diamidinas aromáticas
Issue Date: 2010
Publisher: Cambridge University Press
Citation: BATISTA, D. G. J. et al. Biological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi. Parasitology, v.137, p.251-259, 2010.
DOI: 10.1017/S0031182009991223
ISSN: 0031-1820
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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