Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

Soeiro, Maria de Nazaré Correia; Dantas, A.P.; Daliry, Anissa; Silva, Cristiane F. da; Batista, D. G. J.; Souza, Elen Mello de; Oliveira, Gabriel Melo de; Salomão, Kelly; Batista, Marcos Meuser; Pacheco, Michelle G.O; Silva, Patrícia Bernardino da; Santa‐Rita, Ricardo M.; Barreto, Rubem F. S. Menna; Boykin, David W.; Castro, Solange L. de

doi:10.1590/s0074-02762009000900040

Cited by 36 publications

(34 citation statements)

References 92 publications

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“…According to our present results, we could not find any correlation between the localisation and higher accumulation of these dicationic fluorescent compounds within the T. cruzi kDNA and their trypanocidal activity, which we also found in another recent study of other dicationic compounds (Daliry et al 2009). In fact, previous reports on African trypanosomes also could not correlate either intracellular accumulation or sub cellular localisation and distribution of aza analogs and diphenyl furans with their in vitro activities (Mathis et al 2007).…”

Section: Discussionsupporting

confidence: 51%

“…1) were synthesised in the laboratory of R.R.T. and the previously reported protocol (Daliry et al 2009) was used to assess the effectiveness of aromatic compounds with different shapes, cationic centres and effective motifs. Stock solutions of the drugs (5 mM) were freshly prepared in dimethyl sulfoxide and the final solvent concentration in the assays never exceeded 0.6%, which is not toxic for either parasites or mammalian cells.…”

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confidence: 99%

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The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

Silva

Batista

et al. 2010

Mem. Inst. Oswaldo Cruz

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Trypanosoma cruzi is a parasite that causes Chagas disease, which affects millions of individuals in endemic areas of Latin America. One hundred years after the discovery of Chagas disease, it is still considered a neglected illness because the available drugs are unsatisfactory. Aromatic compounds represent an important class of DNA minor groove-binding ligands that exhibit potent antimicrobial activity. This study focused on the in vitro activity of 10 aromatic dicationic compounds against bloodstream trypomastigotes and intracellular forms of T. cruzi. Our data demonstrated that these compounds display trypanocidal effects against both forms of the parasite and that seven out of the 10 compounds presented higher anti-parasitic activity against intracellular parasites compared with the bloodstream forms. Additional assays to determine the potential toxicity to mammalian cells showed that the majority of the dicationic compounds did not considerably decrease cellular viability. Fluorescent microscopy analysis demonstrated that although all compounds were localised to a greater extent within the kinetoplast than the nucleus, no correlation could be found between compound activity and kDNA accumulation. The present results stimulate further investigations of this class of compounds for the rational design of new chemotherapeutic agents for Chagas disease

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Section: Discussionsupporting

confidence: 51%

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confidence: 99%

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

Silva

Batista

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…Many aspects of T. cruzi infection have been studied using mouse models, including the infectivity of various tissues (Lenzi et al 1996), the presence of cardiac inflammatory lesions (Marinho et al 1999, Andrade et al 2006, Pavanelli et al 2010, the disturbance of the cardiac electrical conduction system (Eickhoff et al 2010), acute kidney injury (AKI) (Oliveira et al 2009b) and the efficacy of drug treatment regimens (Soeiro et al 2009). However, there are significant differences between the natural disease and experimental models.…”

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confidence: 99%

Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters

Silva

Castro

Alves

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…Antimalarial drugs have been shown to be effective against a broad range of parasitic diseases, such as trypanosomiasis, leishmaniasis, amoebiasis, and/or fungal infections (21,(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Effects of Artemether, Artemisinine, Albendazole, and Their Combinations on Echinococcus granolosus Protoscoleces

Mohammadnejad

Ghaffarifar

Dalimi

et al. 2016

Jundishapur J Nat Pharm Prod

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Background: Hydatidosis caused by Echinococcus granulosusus remains an important parasitic disease, mainly in the Mediterranean region, in human and veterinary medicine. Many protoscolicidal agents have been used to treat it, but most of them are not safe and effective due to their undesirable side effects. Objectives: The aim of the present work was to evaluate the in vitro efficacy of the antihelminths artemether, artemisinine, albendazole, and drug combinations against Echinococcus granulosusus protoscoleces. Materials and Methods: Echinococcus granulosus protoscoleces were aseptically removed from liver hydatid cysts in sheep. Drugs were used at the following final concentrations: 1, 2.5, 5, 10, 25, 50, 100, and 200 μg/mL for 15 days. The viability of protoscoleces was confirmed by Eosine 0.1%. Results: In this case, the protoscolicidal effect of artemether and its combinations was significantly (P < 0.05) higher than other groups; the maximum protoscolicidal effect was found with 200 μg/mL of artemether after 4 days whereas albendazole killed protoscoleces on the 7th day post-incubation. Surprisingly, the incubation of protoscoleces with artemisinine exhibited promising results, as only artemisinine was more effective against evaginated protoscoleces on the 9th day. The maximum effect of two drugs combined belonged to artemether and artemisinine. Conclusions:The obtained outcome demonstrated the desirable effect of artemether against Echinococcus granulosus protoscoleces. With regard to artemisinine's astonishing results, it seems that artemisinine can be a striking drug for tissue and metacestode forms of hydatidosis in human and animal models. However, further investigations into the in vivo experiments are proposed.

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Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

Abstract: Chagas disease, which is caused by the intracellular parasite

Cited by 36 publications

References 92 publications

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters

In Vitro Effects of Artemether, Artemisinine, Albendazole, and Their Combinations on Echinococcus granolosus Protoscoleces

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