| Effects of the calpain inhibitor MDL28170 on the clinically relevant forms of Trypanosoma cruzi in vitro. | |
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MedLine Citation:
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PMID: 20457672 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: There is a general lack of effective and non-toxic chemotherapeutic agents for treating Chagas' disease. In the present work, we evaluated the in vitro activity of the calpain inhibitor MDL28170 against Trypanosoma cruzi relevant clinical forms. METHODS: The effect of MDL28170 on bloodstream trypomastigotes at different concentrations was assessed by counting the parasites in a Neubauer chamber, which allowed the determination of IC(50) values. Subsequently, parasite-macrophage interaction was assessed by two approaches: (i) peritoneal mouse macrophages were pre-infected with trypomastigotes for 3 h and then treated daily for 72 h with MDL28170; or (ii) bloodstream trypomastigotes were pre-treated with the calpain inhibitor for 1 h and then subjected to the infection assay. RESULTS: MDL28170 was capable of significantly reducing the viability of bloodstream trypomastigotes, presenting an IC(50)/24 h value of 20.4 microM. Also, parasites pre-treated with the inhibitor, at subinhibitory drug concentrations, prior to macrophage infection presented a clear dose-dependent inhibition profile, where the inhibition increased from 20% to 50% (in relation to control) as MDL28170 concentration rose from 6.25 to 50 microM. In addition, macrophages experimentally infected with T. cruzi that were treated with the calpain inhibitor presented a significant reduction in the percentage of infection even at the lowest concentrations (6.25 microM). CONCLUSIONS: These data may contribute to the study of the calpains in T. cruzi infection and add new in vitro insights into the possibility of exploiting calpains as promising targets to treat Chagas' disease. |
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Authors:
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Vítor Ennes-Vidal; Rubem F S Menna-Barreto; André L S Santos; Marta H Branquinha; Claudia M d'Avila-Levy |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-10 |
Journal Detail:
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Title: The Journal of antimicrobial chemotherapy Volume: 65 ISSN: 1460-2091 ISO Abbreviation: J. Antimicrob. Chemother. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-10 Completed Date: 2010-09-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7513617 Medline TA: J Antimicrob Chemother Country: England |
Other Details:
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Languages: eng Pagination: 1395-8 Citation Subset: IM |
Affiliation:
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Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antiprotozoal Agents / pharmacology* Chagas Disease / parasitology Dipeptides / pharmacology* Glycoproteins / pharmacology* Inhibitory Concentration 50 Macrophages, Peritoneal / parasitology Mice Microbial Viability / drug effects Trypanosoma cruzi / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Antiprotozoal Agents; 0/Dipeptides; 0/Glycoproteins; 0/calpain inhibitors; 88191-84-8/calpain inhibitor III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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