Corroboración experimental de la actividad antileishmaniásica de nuevos compuestos identificados mediante estudios in silico
Fecha
2019
Autores
Ramírez Abreu, Ailín
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Editor
Universidad Central "Marta Abreu" de Las Villas. Facultad de Química y Farmacia. Departamento de Licenciatura en Ciencias Farmacéuticas
Resumen
La leishmaniasis es una enfermedad causada por parásitos protozoos del género Leishmania, clasificada por la Organización Mundial de la Salud como una de las infecciones tropicales desatendidas más importantes. Los fármacos disponibles en la terapéutica no son suficientemente efectivos, presentan una alta frecuencia de efectos citotóxicos serios, son costosos y la resistencia parasitaria ha emergido de forma creciente. A partir de esta problemática se hace necesaria la identificación de nuevas entidades moleculares con propiedades antileishmaniásicas. En el presente trabajo se llevó a cabo un protocolo de cribado virtual con el propósito de identificar nuevos compuestos potencialmente activos frente a Leishmania spp., empleando herramientas quimio-informáticas. Se confeccionaron dos bases de datos que incluían Ingredientes Farmacéuticos Activos del Cuadro Básico de Medicamento de Cuba, compuestos de origen vegetal y de síntesis químicas. Se procedió al cribado virtual de las bases de datos empleando modelos de predicción obtenidos por las técnicas de clasificación: IBk, J48, MLP y SVM para L. amazonensis, L. infantum y L. major. Los compuestos selectos como potencialmente activos por el ensamblado empleado para L. amazonensis mostraron actividad in vitro frente promastigotes de dicha especie con CI50 inferiores a 1 μg/mL y a la vez presentaron citotoxicidad para macrófagos peritoneales de ratón BALB/c con índice de selectividad mayor que 10.
Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, classified by the World Health Organization as one of the most important neglected tropical infections. The drugs available in therapeutics are not sufficiently effective, have a high frequency of serious cytotoxic effects, are expensive and parasitic resistance has emerged increasingly. Based on this problem, it is necessary to identify new molecular entities with antileishmanial properties. In the present work, a virtual screening protocol was carried out in order to identify new compounds potentially active against Leishmania spp. using chemo-informatic tools. Two databases were created that included Active Pharmaceutical Ingredients of the Basic Table of Medicine of Cuba, compounds of vegetable origin and chemical synthesis. The databases were screened virtually using prediction models obtained by the following classification techniques: IBk, J48, MLP and SVM for L. amazonensis, L. infantum and L. major. The compounds selected as potentially active by the assembly used for L. amazonensis showed in vitro activity against promastigotes of this species with CI50 lower than 1 μg/mL and at the same time presented cytotoxicity for peritoneal macrophages of BALB/c mouse with selectivity index higher than 10
Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, classified by the World Health Organization as one of the most important neglected tropical infections. The drugs available in therapeutics are not sufficiently effective, have a high frequency of serious cytotoxic effects, are expensive and parasitic resistance has emerged increasingly. Based on this problem, it is necessary to identify new molecular entities with antileishmanial properties. In the present work, a virtual screening protocol was carried out in order to identify new compounds potentially active against Leishmania spp. using chemo-informatic tools. Two databases were created that included Active Pharmaceutical Ingredients of the Basic Table of Medicine of Cuba, compounds of vegetable origin and chemical synthesis. The databases were screened virtually using prediction models obtained by the following classification techniques: IBk, J48, MLP and SVM for L. amazonensis, L. infantum and L. major. The compounds selected as potentially active by the assembly used for L. amazonensis showed in vitro activity against promastigotes of this species with CI50 lower than 1 μg/mL and at the same time presented cytotoxicity for peritoneal macrophages of BALB/c mouse with selectivity index higher than 10
Descripción
Palabras clave
Organización Mundial de la Salud, Leishmaniasis, Enfermedades Parasitarias, Medicina Verde, Fármacos Antileishmaniásicos, Estudios QSPR/QSAR, Descriptores Moleculares