Biological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi

dc.creatorBatista, D. G. J.
dc.creatorPacheco, M. G. O.
dc.creatorKumar, A.
dc.creatorBranowska, D.
dc.creatorIsmail, M. A.
dc.creatorHu, L.
dc.creatorBoykin, D. W.
dc.creatorSoeiro, Maria Nazaré C.
dc.date2018-12-20T11:25:44Z
dc.date2018-12-20T11:25:44Z
dc.date2010
dc.date.accessioned2023-09-27T00:04:15Z
dc.date.available2023-09-27T00:04:15Z
dc.identifierBATISTA, D. G. J. et al. Biological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi. Parasitology, v.137, p.251-259, 2010.
dc.identifier0031-1820
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/30711
dc.identifier10.1017/S0031182009991223
dc.identifier1469-8161
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8897124
dc.descriptionNo 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.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherCambridge University Press
dc.rightsrestricted access
dc.subjectTrypanosoma cruzi
dc.subjectDoença de Chagas
dc.subjectQuimioterapia
dc.subjectdiamidinas aromáticas
dc.subjectTrypanosoma cruzi
dc.subjectChagas Disease
dc.subjectchemotherapy
dc.subjectaromatic diamidines
dc.titleBiological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi
dc.typeArticle


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