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Acoplamiento molecular in silico de compuestos de Moringa oleifera Lam. con el sitio catalítico y de unión a FAD-NADPH de la tripanotiona reductasa de Leishmania infantum
In silico molecular docking of Moringa oleifera Lam. compounds with the catalytic and FAD-NADPH-binding site of trypanothione reductase from Leishmania infantum
Docking molecular in silico de compostos de Moringa oleifera Lam. com o sítio catalítico e de ligação FAD-NADPH da tripanotiona redutase de Leishmania infantum
Palabras clave:
moringa, fitoconstituyentes, acoplamiento molecular, leishmania, tripanotiona reductasa (es)moringa, phytoconstituents, molecular docking, leishmania, trypanothione reductase (en)
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Introducción: la búsqueda computacional de nuevos compuestos para futuras terapias farmacológicas contra la leishmaniasis se ha enfocado en la tripanotiona reductasa. Esta enzima es esencial para la supervivencia de Leishmania infantum, su ausencia en el huésped y su alta farmacobilidad la convierten en un buen objetivo para el desarrollo de nuevas drogas. El uso de plantas como fitoterapéuticos ha sido ampliamente investigado debido a que han demostrado importantes actividades leishmanicidas. Objetivo: analizar las interacciones de los compuestos de Moringa oleifera con el sitio catalítico y de unión a FAD-NADPH de la tripanotiona reductasa de L. infantum empleando el acoplamiento molecular. Método: fueron evaluados treinta compuestos descritos en la especie de M. oleifera, estas se sometieron a ensayos computacionales de acoplamiento molecular semiflexible con el sitio catalítico de la enzima y el dominio de unión FAD-NADPH. Resultados: se evidencia que los compuestos que demostraron valores favorables de energía de unión con el sitio catalítico de la enzima fueron la apigenina, la quercetina, la miricetina y la isorhamnetina. Mientras que los compuestos que presentaron uniones favorables con el dominio FAD-NADPH fueron la rutina y el ácido 5,6,7,8-tetrahidrofólico. Conclusión: estos hallazgos sugieren que los compuestos de M. oleifera mencionados presentan afinidades de unión por el sitio catalítico y el dominio de unión FAD-NADPH de la tripanotiona reductasa de L. infantum, pudiendo ser utilizados para pruebas in vitro.
Introduction: Computational search of new compounds for future drug therapies against leishmaniasis has focused on trypanothione reductase. This enzyme is essential for the survival of Leishmania infantum, the absence in the host and its high druggability make it a good target for the development of new drugs. The use of plants for phytotherapeutics purpose has been widely investigated due to its important leishmanicidal activities. Aim: The aim of this study was to analyze the interactions of Moringa oleifera compounds to the catalytic and FAD-NADPH binding site of L. infantum trypanothione reductase using molecular docking. Method: Thirty compounds described in M. oleifera species were evaluated and subjected to computational semi-flexible molecular docking assays with the catalytic site and the FAD-NADPH binding domain of the enzyme. Results: The results show that the compounds that demonstrated favorable binding energy values with the catalytic site of the enzyme were apigenin, quercetin, myricetin and isorhamnetin. While the compounds that exhibited favorable binding with the FAD-NADPH domain were rutin and 5,6,7,8-tetrahydrofolic acid. Conclusion: These findings suggest that mentioned M. oleifera compounds present binding affinities for the catalytic site and the FAD-NADPH binding domain of L. infantum trypanothione reductase and could be used for in vitro assays.Introduction: Computational search of new compounds for future drug therapies against leishmaniasis has focused on trypanothione reductase. This enzyme is essential for the survival of Leishmania infantum, the absence in the host and its high druggability make it a good target for the development of new drugs. The use of plants for phytotherapeutics purpose has been widely investigated due to its important leishmanicidal activities. Aim: The aim of this study was to analyze the interactions of Moringa oleifera compounds to the catalytic and FAD-NADPH binding site of L. infantum trypanothione reductase using molecular docking. Method: Thirty compounds described in M. oleifera species were evaluated and subjected to computational semi-flexible molecular docking assays with the catalytic site and the FAD-NADPH binding domain of the enzyme. Results: The results show that the compounds that demonstrated favorable binding energy values with the catalytic site of the enzyme were apigenin, quercetin, myricetin and isorhamnetin. While the compounds that exhibited favorable binding with the FAD-NADPH domain were rutin and 5,6,7,8-tetrahydrofolic acid. Conclusion: These findings suggest that mentioned M. oleifera compounds present binding affinities for the catalytic site and the FAD-NADPH binding domain of L. infantum trypanothione reductase and could be used for in vitro assays.
Introdução: a busca computacional por novos compostos para futuras terapias farmacológicas contra a leishmaniose tem se concentrado na tripanotiona redutase. Esta enzima é essencial para a sobrevivência de Leishmania infantum, sua ausência no hospedeiro e sua alta farmacobilidade a tornam um bom alvo para o desenvolvimento de novos fármacos. O uso de plantas como fitoterápicos tem sido amplamente investigado por apresentarem importantes atividades leishmanicidas. Objetivo: o objetivo deste estudo foi analisar as interações dos compostos da Moringa oleifera com o sítio catalítico e de ligação FAD-NADPH da tripanotiona redutase de L. infantum usando docking molecular. Método: foram avaliados trinta compostos descritos na espécie M. oleifera, os quais foram submetidos a testes computacionais de docking molecular semi-flexível com o sítio catalítico da enzima e o domínio de ligação FAD-NADPH. Resultados: fica evidente que os compostos que demonstraram valores de energia de ligação favoráveis com o sítio catalítico da enzima foram apigenina, quercetina, miricetina e isorhamnetina. Enquanto os compostos que apresentaram ligações favoráveis com o domínio FAD-NADPH foram a rutina e o ácido 5,6,7,8-tetraidrofólico. Conclusão: esses achados sugerem que os compostos de M. oleifera mencionados possuem afinidades de ligação para o sítio catalítico e o domínio de ligação FAD-NADPH da tripanotiona redutase de L. infantum, e podem ser usados para testes in vitro.
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