Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase

Blumenstiel, Klaus; Schöneck, Ralf; Yardley, Vanessa; Croft, Simon L.; Krauth‐Siegel, R. Luise

doi:10.1016/s0006-2952(99)00264-6

Cited by 97 publications

(104 citation statements)

References 38 publications

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“…3,4 The biological action of nitrofurazone ͑NF͒ has been reported on T. cruzi through trypanothione reductase inhibition, an enzyme found in the parasite rather than in the host. 5,7 It is generally accepted that the nitro radical anion and hydroxylamine derivative are the main species responsible for some nitroheterocyclic compounds' cytotoxic action. 8,9 As a result, electrochemical studies can be relevant for the comprehension of the redox cycles involved in these biological processes.…”

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confidence: 99%

Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH

La-Scalea

Trossini

Menezes

et al. 2009

J. Electrochem. Soc.

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Nitrofurazone ͑NF͒ presents activity against Chagas' disease, yet it has a high toxicity. Its analog, hydroxymethylnitrofurazone ͑NFOH͒, is more potent against Trypanosoma cruzi and much less toxic than the parent drug, NF. The electrochemical reduction of NFOH in an aqueous medium using a glassy carbon electrode ͑GCE͒ is presented. By cyclic voltammetry in anacidic medium, one irreversible reduction peak related to hydroxylamine derivative formation was registered, being linearly pH dependent. However, from pH Ͼ 7, a reversible reduction peak at a more positive potential appears and corresponds to the formation of a nitro radical anion. The radical-anion kinetic stability was evaluated by Ip a /Ip c the current ratio of the R-NO 2 /R-NO 2•− redox couple. The nitro radical anion decays with a second-order rate constant ͑k 2 ͒ of 6.07, 2.06, and 1.44͑ϫ10 3 ͒ L mol −1 s −1 corresponding to pH 8.29, 9.29, and 10.2, respectively, with a corresponding half-time life ͑t 1/2 ͒ of 0.33, 0.97, and 1.4 s for each pH value. By polishing the GCE surface with diamond powder and comparing with the GCE surface polished with alumina, it is shown that the presence of alumina affects the lifetime of the nitro radical anion.

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confidence: 99%

Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH

La-Scalea

Trossini

Menezes

et al. 2009

J. Electrochem. Soc.

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“…T A B en que la glucosa es convertida a piruvato (14). Posteriormente, el piruvato experimenta un proceso de descarboxilación oxidativa, el cual involucra la deshidrogenación de la dihidrolipoamida mediante la enzima lipoamida deshidrogenasa (LipDH), componente esencial de los complejos mitocondriales piruvato deshidrogenasa y 2 oxoglutarato deshidrogenasa (15).…”

Section: Resultsunclassified

Expresión diferencial entre estadios de Trypanosoma cruzi I en el aislamiento de un paciente con cardiomiopatía chagásica crónica de zona endémica de Santander, Colombia

2011

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Introducción. Trypanosoma cruzi es el agente causal de la enfermedad de Chagas. Durante la infección en los huéspedes mamíferos, se observan dos formas del parásito: tripomastigotes y amastigotes. En el curso de la diferenciación del parásito cada estadio expresa un patrón de proteínas específicas de fase, las cuales son responsables de sus características morfológicas, bioquímicas y biológicas, que podrían estar determinando un papel importante en la capacidad infecciosa, virulencia y supervivencia del parásito. Objetivo. Analizar la expresión diferencial entre los estadios tripomastigote y amastigote de un aislamiento de T. cruzi I, utilizando la electroforesis en dos dimensiones y la identificación de las proteínas diferencialmente expresadas mediante espectrometría de masas. Materiales y métodos. Se utilizó un clon del aislamiento MHOM/07/338 de T. cruzi I y, mediante electroforesis en dos dimensiones, se compararon los perfiles proteicos de los estadios tripomastigote y amastigote del parásito. Las imágenes se analizaron con el software PDQuest y las proteínas diferencialmente expresadas se identificaron por MALDI TOF o LC MS/MS. Resultados. Los geles bidimensionales mostraron un promedio de 325 manchas proteicas en cada estadio. En los análisis comparativos se detectaron 21 manchas "sobreexpresadas" en el estadio tripomastigote y 30, en el estadio amastigote. Se seleccionaron 16 proteínas para identificación por espectrometría de masas y se clasificaron en diferentes categorías funcionales. Conclusiones. Las proteínas exclusivas de T. cruzi relacionadas, principalmente, con metabolismo glucolítico y ensamble del citoesqueleto, fueron las que presentaron una mayor expresión diferencial entre los estadios tripomastigote y amastigote del parásito. Estas proteínas podrían ser utilizadas para el diseño de fármacos.Palabras clave: Trypanosoma cruzi, enfermedad de Chagas, proteómica, cardiomiopatía chagásica, Colombia. Differential protein expression in developmental stages of Trypanosoma cruzi I isolated from a patient with chronic chagasic cardiomyopathyIntroduction. Trypanosoma cruzi is the causative agent of Chagas disease. During infection in mammalian hosts, two main forms of the parasite are observed: trypomastigotes and amastigotes. During differentiation, each stage of the parasite expresses a pattern of proteins specific to each phase---proteins which are responsible for the cell's morphological, biochemical and biological properties. These properties ultimately govern the infectivity, virulence and survival of the parasite. Objective. A differential expression analysis was conducted to compare trypomastigote and amastigote stages of T. cruzi I isolate, and to identify proteins differentially expressed by means of mass spectrometry. Materials and methods. A T. cruzi clone of the strain MHOM/07/338 was used to analyze the differential expression between trypomastigote stages of a T. cruzi isolate, using two-dimensional electrophoresis and identification of diferentially expressed proteins by mass spectro...

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“…However, significant toxicity, as indicated by cell viabilities less than 70%, was observed for nifuroxazide concentrations greater than 0.03 mM (8 lg/mL) following incubation for 4 h. Blumenstiel et al (1999), using nitrofuran derivatives with activity against Trypanosoma cruzi, demonstrated that nifuroxazide and nifuprazine had no toxic effects on mammalian cells (macrophages) following incubation for 3 days at concentrations lower than 10 mM. In a cytotoxicity study conducted by Rossa et al (2003), the nitrofuran quinifuril showed high toxicity in rat leukemic cells in vitro and low toxicity in non-tumor animal cells.…”

Section: Substancementioning

confidence: 97%

“…Therefore, it is plausible that the toxicity of nitro compounds is dependent on multiple factors, including chemical structure, exposure time, dosage and the type of cell. Caco-2 cells were more susceptible to 5-nitro-heterocyclic compounds than were macrophages (Blumenstiel et al, 1999), probably because the former are derived from a carcinoma, i.e., they are mammalian tumor cells. As these cytotoxic assays were performed prior to their cellular maturation into epithelial cells, it is expected that these cells would have greater viability when they are differentiated.…”

Section: Substancementioning

confidence: 98%

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

Fernandes

Gonçalves

Scotti

et al. 2012

Toxicology in Vitro

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Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase

Cited by 97 publications

References 38 publications

Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH

Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH

Expresión diferencial entre estadios de Trypanosoma cruzi I en el aislamiento de un paciente con cardiomiopatía chagásica crónica de zona endémica de Santander, Colombia

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

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