Specific chemotherapy of Chagas disease: controversies and advances

Urbina, Julio A.; Docampo, Roberto

doi:10.1016/j.pt.2003.09.001

Cited by 507 publications

(473 citation statements)

References 51 publications

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“…Therefore, there is an urgent need to develop new, safe and effective therapeutic alternatives that are also cost-effective. [10][11][12][13] Multiple anti-infective activities are well known for quinoxaline derivatives. [14,15] Our group has vast experience in the synthesis and biological evaluation of multiple quinoxaline 1,4-di-Noxide derivatives, having identified a broad spectrum of anti-infective activities.…”

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confidence: 99%

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Torres

Moreno‐Viguri

Galiano

et al. 2013

European Journal of Medicinal Chemistry

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ABSTRACT. As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with 2 fluoro groups at the 6-and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups, possessed a greater ease of reduction of the N-oxide groups.

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confidence: 99%

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Torres

Moreno‐Viguri

Galiano

et al. 2013

European Journal of Medicinal Chemistry

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“…In particular, the Southern Cone initiative has successfully interrupted reservoirto-human and human-to-human propagation of the disease in Uruguay, Chile and Brazil in recent years and has led to a marked reduction of the overall prevalence and the population at risk (Dias et al 2002, Schofield et al 2006. However, many challenges remain before full control or elimination of the disease can be achieved among them, inequality of the control programs in the various endemic areas (Attaran 2006, Schofield et al 2006, Aguilar et al 2007, Guhl 2007, limitations of currently available specific chemotherapy, and insufficient treatment coverage for those currently infected with the aetiological agent, the parasitic protozoan Trypanosoma cruzi (Urbina & Docampo 2003, Pinto Dias 2006, Jannin & Villa 2007, Tarleton et al 2007, Rassi et al 2009). …”

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Ergosterol biosynthesis and drug development for Chagas disease

Urbina

2009

Mem. Inst. Oswaldo Cruz

193

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“…El panorama se complica aún más por la ineficiente quimioterapia que existe para esta enfermedad, ya que el benzonidazol y el nifurtimox son efectivos sólo bajo ciertas circunstancias, tienen diversos efectos secundarios (6,29) y pueden generar resistencia en T. cruzi (13)(14)(15), además de la existencia de cepas naturalmente resistentes a dichos medicamentos (8).…”

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“…En los últimos años, diversos estudios se han enfocado en la búsqueda y evaluación de nuevas estrategias quimioterapéuticas para tratar esta enfermedad (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Sin embargo, luego de más de 100 años de descubrirse la enfermedad y de más de 40 de implementarse el tratamiento, las únicas alternativas existentes son los medicamentos mencionados anteriormente (38).…”

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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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Specific chemotherapy of Chagas disease: controversies and advances

Cited by 507 publications

References 51 publications

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Ergosterol biosynthesis and drug development for Chagas disease

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

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