Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host

Maya, Juan Diego; Cassels, Bruce K.; Iturriaga-Vásquez, Patricio; Ferreira, Jorge; Faúndez, Mario; Galanti, Norbel; Ferreira, Arturo; Morello, Antonio

doi:10.1016/j.cbpa.2006.03.004

Cited by 316 publications

(295 citation statements)

References 198 publications

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“…Both are trypanocidal to all forms of the parasite (Maya et al, 2007;Maya et al, 1997;Urbina, 2009b). Nx and Bz act through the formation of free radicals and/or electrophilic metabolites, affecting all macromolecules of the parasite (Maya et al, 2003).…”

Section: Treatment Of Chagas Diseasementioning

confidence: 99%

“…Numerous natural and synthetic chemical compounds with potential trypanocidal activity are being added to the list, including allopurinol and its analogues, ketoconazole and itraconazole (antifungal imidazoles), quinones, diverse nitroheterocyclic derivatives, antioxidants and other drugs in clinical use, such as phenothiazines (Apt et al, 2005;Maya et al, 2007;Urbina, 2009b). Some compounds, including sterol biosynthesis, cysteine protease and pyrophosphate metabolism inhibitors, have completed pre-clinical studies and are poised for clinical trials in Chagas disease patients (Reithinger et al, 2009;Urbina, 2009a).…”

Section: Treatment Of Chagas Diseasementioning

confidence: 99%

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Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Section: Treatment Of Chagas Diseasementioning

confidence: 99%

Section: Treatment Of Chagas Diseasementioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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“…En este sentido, hoy en día se están haciendo muchos esfuerzos por entender los mecanismos de acción del benzonidazol y el nifurtimox, con el fin de mejorar el uso de estos medicamentos (7,12,13,39,40). Si bien es cierto que se han producido algunos avances en este sentido (7,12,13,41,42), en la actualidad aún no se han podido esclarecer parámetros tales como cuáles son las concentraciones del medicamento para considerar las cepas como resistentes y cuál es la relación entre los mecanismos de resistencia natural y la inducida.…”

Section: Discussionunclassified

Sensibilidad al benzonidazol de cepas de Trypanosoma cruzi sugiere la circulación de cepas naturalmente resistentes en Colombia

Mejía-Jaramillo¹,

Fernández²,

Montilla³

et al. 2012

biomedica

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Introducción. La enfermedad de Chagas, causada por Trypanosoma cruzi, es uno de los problemas más graves de salud pública en el continente americano. El benzonidazol es uno de los dos medicamentos utilizados para tratar la enfermedad de Chagas. Sin embargo, la variación de la sensibilidad del parásito a este medicamento es una de las principales causas del fracaso del tratamiento. Objetivo. Evaluar la sensibilidad in vitro al benzonidazol de cepas colombianas de T. cruzi de diferentes orígenes y procedencia geográfica. Materiales y métodos. Treinta y tres cepas colombianas de T. cruzi aisladas de humanos, vectores y mamíferos, se analizaron in vitro mediante el micrométodo enzimático de MTT para determinar la concentración inhibitoria 50 (CI 50 ) al benzonidazol. Se estudió la correlación entre la sensibilidad in vitro al medicamento y diferentes parámetros biológicos y eco-epidemiológicos. Resultados. El análisis de sensibilidad al medicamento indicó que el 36 % de las cepas eran sensibles, el 48 %, parcialmente resistentes y, el 16 %, resistentes al benzonidazol. Los análisis de correlación entre las CI 50 con algunos parámetros biológicos y eco-epidemiológicos, mostraron diferencias en cuanto a la sensibilidad según el origen biológico y el área geográfica de procedencia de la cepa. Conclusiones. Existe una gran variabilidad en cuanto a la sensibilidad al benzonidazol de las cepas circulantes de T. cruzi en Colombia, lo cual sugiere la presencia de cepas naturalmente resistentes en el país. Palabras clave:Trypanosoma cruzi, enfermedad de Chagas/terapia, inmunidad innata, Colombia. Trypanosoma cruzi strains resistant to benznidazole occurring in ColombiaIntroduction. Chagas disease caused by Trypanosoma cruzi is one of the most serious public health problems in the Americas. Benznidazole is one of two drugs used to treat Chagas' disease. However, the variation in susceptibility of the parasite to this drug is one of the main causes of treatment failure. Objective. The in vitro susceptibility to benznidazole was assessed in Colombian strains of T. cruzi from several sources and geographical regions. Materials and methods. Thirty-three Colombian T. cruzi strains were isolated from humans, vectors and mammals. These were analyzed in vitro by the MTT enzymatic micromethod to determine the IC 50 to benznidazole. Additionally, the in vitro susceptibility was correlated with several biological and ecoepidemiological parameters. Results. Thirty-six percent of the strains were considered to be sensitive, 48% partially resistant, and 16% were resistant. Correlations between the IC 50 and several biological and eco-epidemiological parameters indicated that differences in susceptibility depended on the biological source and geographical origin of the strain. Conclusions. A high degree of variability exists in the susceptibility to benznidazole of T. cruzi strains in Colombia. The distribution data indicate the presence and circulation of naturally resistant strains.

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“…Determining the efficacy or optimum concentration of a tested drug is extremely important and acquiring information about its effect on parasite biology and parasite interaction with the host cell is of great value (Maya et al, 2007).…”

Section: Resultsmentioning

confidence: 99%