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1.
Int. microbiol ; 22(1): 143-154, mar. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-184822

RESUMO

Anthroponotic visceral leishmaniasis is a life-threatening disease caused by Leishmania donovani (Kinetoplastida: Trypanosomatidae) in East Africa and the Indian subcontinent. Unlike promastigote growth and differentiation in the sand fly gut or in axenic culture, L. donovani promastigote-into-amastigote development has been studied by high-throughput gene expression profiling. In this study, we have identified abundant constitutive proteins in axenically cultured promastigotes by two-dimension electrophoresis and matrix-assisted laser desorption-ionization tandem time-of-flight (MALDI-TOF/TOF) mass spectrometry. Most proteins involved in the trypanothione-based redox antioxidant system are expressed constitutively throughout axenic L. donovani promastigote growth and differentiation (tryparedoxin, trypanothione peroxidase, generic peroxidoxin, iron-superoxide dismutase, and elongation factor 1ß). These findings are in agreement with previous data on other Old World species (i.e., L. major and L. infantum), whereas New World species (i.e., L. amazonensis and L. pifanoi) and Crithidia fasciculata show different expression patterns


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Assuntos
Leishmania donovani/química , Leishmania donovani/crescimento & desenvolvimento , Proteoma/análise , Proteínas de Protozoários/análise , Eletroforese em Gel Bidimensional , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
An. R. Acad. Farm ; 82(3): 317-323, jul.-sept. 2016. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-158074

RESUMO

La leishmaniasis se encuentra entre las seis enfermedades más importantes en el Programa Especial de Investigación y Adiestramiento en Enfermedades Tropicales (TDR) de la OMS. Los fármacos disponibles actualmente presentan altas toxicidades o se han desarrollado resistencias para los mismos, de modo que buscar nuevos compuestos que posean actividad anti-leishmánica es una opción quimioterapéutica atractiva. En el presente estudio hemos utilizado la topología molecular y el análisis de regresión multilineal para el desarrollo de un modelo QSAR capaz de predecir la actividad frente a L. major y L. donovani de un grupo de compuestos derivados del pirrol [1,2-alfa] quinoxalina. Validados los modelos topológicos seleccionados, se ha realizado un cribado molecular y se han seleccionado nuevos derivados de la quinoxalina con potencial actividad anti-leishmánica


Leishmaniasis is present among the six greatest diseases reported in the WHO's Special Programme for Research and Training in Tropical Diseases (TDR). Nowadays, the available drugs show high toxicities or resistance has been developed. Therefore the search of new compounds that possess anti-leishmania activity is an attractive chemotherapeutic option. In the present study we have applied molecular topology and multilineal regression analysis to develop a QSAR model able to predict the activity of a series of pyrrolo [1,2-alfa] quinoxaline derived compounds against L. major and L. donovani. Once validated the selected topological models, a molecular screening has been performed and new quinoxaline derivatives with potential anti-leishmania activity have been selected


Assuntos
Humanos , Pirróis/toxicidade , Quinoxalinas/toxicidade , Leishmaniose/tratamento farmacológico , Antiprotozoários/farmacologia , Leishmania donovani/patogenicidade , Leishmania major/patogenicidade
6.
An. R. Acad. Farm ; 74(3): 345-367, jul. 2008. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-67775

RESUMO

Se ha desarrollado un modelo topológico-matemático encaminado a buscarnuevos compuestos derivados del 3,5 dinitrobenceno sulfonamida y/o benzamidaactivos frente a Leishmania. Utilizando el análisis lineal discriminante y el análisisde regresión multilineal se ha obtenido un modelo capaz de identificar la actividaddel 90% de los compuestos estudiados. Tras realizar un barrido virtual se proponennuevas estructuras potencialmente activas frente a L donovani


A topological-mathematical model has been arranged to search for newderivatives of 3,5-dinitrobenzene sulphonamide and/or benzamide, active againstL. donovani. By using linear discriminant analysis as well as multilinear regression,a model capable to identify the activity of 90% of the analyzed compounds hasbeen achieved. After carrying out a virtual screening based upon such a model, newstructures potentially active against the parasite are proposed


Assuntos
Humanos , Biologia Molecular/métodos , Leishmania/química , Modelos Teóricos , Leishmania donovani/química , Leishmania donovani/microbiologia , Análise Discriminante , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Modelos Logísticos , Análise de Regressão , Imunossupressão/métodos
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