Activity of anticancer compounds against Trypanosoma cruzi-infected mice.

Kinnamon, Kenneth E.; Poon, Bing T.; Hanson, William L.; Waits, Virginia B.

doi:10.4269/ajtmh.1998.58.804

Cited by 20 publications

(12 citation statements)

References 12 publications

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“…Another nitrofuran, furazolidone, is active against T. cruzi in mice (8). Trypanocidal activity has been reported for docetaxel (39), cycloheximide (34), and amiodarone (5). Nelfinavir, an HIV protease inhibitor, is active against Toxoplasma gondii (19).…”

Section: Discussionmentioning

confidence: 99%

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Image-Based High-Throughput Drug Screening Targeting the Intracellular Stage of Trypanosoma cruzi , the Agent of Chagas' Disease

Engel¹,

Ang

Chen

et al. 2010

Antimicrob Agents Chemother

102

117

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Chagas' disease, caused by infection with the parasite Trypanosoma cruzi, is the major cause of heart failure in Latin America. Classic clinical manifestations result from the infection of heart muscle cells leading to progressive cardiomyopathy. To ameliorate disease, chemotherapy must eradicate the parasite. Current drugs are ineffective and toxic, and new therapy is a critical need. To expedite drug screening for this neglected disease, we have developed and validated a cell-based, high-throughput assay that can be used with a variety of untransfected T. cruzi isolates and host cells and that simultaneously measures efficacy against the intracellular amastigote stage and toxicity to host cells. T. cruzi-infected muscle cells were incubated in 96-well plates with test compounds. Assay plates were automatically imaged and analyzed based on size differences between the DAPI (4,6-diamidino-2-phenylindole)-stained host cell nuclei and parasite kinetoplasts. A reduction in the ratio of T. cruzi per host cell provided a quantitative measure of parasite growth inhibition, while a decrease in count of the host nuclei indicated compound toxicity. The assay was used to screen a library of clinically approved drugs and identified 55 compounds with activity against T. cruzi. The flexible assay design allows the use of various parasite strains, including clinical isolates with different biological characteristics (e.g., tissue tropism and drug sensitivity), and a broad range of host cells and may even be adapted to screen for inhibitors against other intracellular pathogens. This high-throughput assay will have an important impact in antiparasitic drug discovery.

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Section: Discussionmentioning

confidence: 99%

“…To address enormous unmet medical needs, there have been recent efforts in "repurposing" drugs (14,15,45,55) from other therapies even for neglected parasitic diseases (5,8,19,27,34,38,39). The current therapeutic drugs for Chagas' (13).…”

Section: Discussionmentioning

confidence: 99%

Image-Based High-Throughput Drug Screening Targeting the Intracellular Stage of Trypanosoma cruzi , the Agent of Chagas' Disease

Engel¹,

Ang

Chen

et al. 2010

Antimicrob Agents Chemother

102

117

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“…9 Their efficacy is also limited to the acute phase of the infection, and it is highly variable so that there is still controversial evidence that patients really benefit from such treatments. 10 A variety of new drugs is thus currently under development, [20][21][22][23][24] and some appear to show promise. However, additional studies are necessary and it will be some time before new treatments become available.…”

Section: Overview Of the Diseasementioning

confidence: 99%

Update on Chagas' disease in Mexico

Dumonteil

1999

Salud pública Méx

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“…However, these drugs have little efficacy (limited to early stages of the infection), and they have serious side effects, so that efforts are needed to identify new treatments (20,41,47). Indeed, Chagas' disease is one of the most neglected diseases in terms of development of new drugs (45).…”

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confidence: 99%

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

et al. 2004

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The mechanisms involved in the pathology of chronic chagasic cardiomyopathy are still debated, and the controversy has interfered with the development of new treatments and vaccines. Because of the potential of DNA vaccines for immunotherapy of chronic and infectious diseases, we tested if DNA vaccines could control an ongoing Trypanosoma cruzi infection. BALB/c mice were infected with a lethal dose (5 ؋ 10 4 parasites) as a model of acute infection, and then they were treated with two injections of 100 g of plasmid DNA 1 week apart, beginning on day 5 postinfection. Control mice had high levels of parasitemia and mortality and severe cardiac inflammation, while mice treated with plasmid DNA encoding trypomastigote surface antigen 1 or Tc24 had reduced parasitemia and mild cardiac inflammation and >70% survived the infection. The efficacy of the immunotherapy also was significant when it was delayed until days 10 and 15 after infection. Parasitological analysis of cardiac tissue of surviving mice indicated that most mice still contained detectable parasite kinetoplast DNA but fewer mice contained live parasites, suggesting that there was efficient but not complete parasite elimination. DNA vaccine immunotherapy was also evaluated in CD1 mice infected with a low dose (5 ؋ 10 2 parasites) as a model of chronic infection. Immunotherapy was initiated on day 70 postinfection and resulted in improved survival and reduced cardiac tissue inflammation. These results suggest that DNA vaccines have strong potential for the immunotherapy of T. cruzi infection and may provide new alternatives for the control of Chagas' disease.

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Activity of anticancer compounds against Trypanosoma cruzi-infected mice.

Cited by 20 publications

References 12 publications

Image-Based High-Throughput Drug Screening Targeting the Intracellular Stage of Trypanosoma cruzi , the Agent of Chagas' Disease

Image-Based High-Throughput Drug Screening Targeting the Intracellular Stage of Trypanosoma cruzi , the Agent of Chagas' Disease

Update on Chagas' disease in Mexico

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

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