Identificación in silico de inhibidores de aldosa reductasa a partir de productos naturales y acoplamiento molecular para la disminución de complicaciones microvasculares asociadas a diabetes mellitus
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2020
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Ediciones Universidad Simón Bolívar
Facultad de Ciencias de la Salud
Facultad de Ciencias de la Salud
Resumen
Introducción: La hiperglucemia en pacientes diabéticos se convierte en una abundante
variedad de complicaciones, tales como la retinopatía diabética, neuropatía, nefropatía y
enfermedades cardiovasculares. La participación de la aldosa reductasa (AR), la enzima
principal en la vía metabólica de los polioles se encuentra inmersa en la progresión de
estas. Considerando los relevantes resultados encontrados en revisiones bibliográficas
acerca del potencial toxico de moléculas sintéticas utilizadas para la inhibición de la AR en
pacientes, en este artículo se plantea una alternativa para la identificación in silico de
moléculas inhibitorias de la AR naturales que presenten una posible reducción de la
toxicidad y efectos adversos en los pacientes. Métodos: Inicialmente se buscó
fitoquímicos (ligandos) con características hipoglucemiantes, antiinflamatorias y
antioxidantes, en la base de datos, posteriormente, se contó con una librería un total de
47 moléculas, de los cuales 26 son fitoquímicos no reportados, 17 reportados naturales y
4 reportados sintéticos, seguidamente fueron procesados junto a la proteína en AutoDock
Tools y el acoplamiento se realizo en AutoDock Vina, finalmente las mejores de cada
grupo se le realizo DM en el software Amber18. Resultados: Del Docking: el mejor
fitoquímicos fue el Anthocyanins con una afinidad por la AR de -10,1 kcal/mol, el mejor
reportados naturales fue Cannabigerolic Acid con una afinidad por la AR de -8,2 kcal/mol y
el mejor los sintéticos reportados fue Alrestatin tiene una afinidad por la AR de -7,6
kcal/mol. De la DM: el mejor de los 3 ligandos estudiados es el anthocyanins con una energía de -33.30 kcal/mol, seguido de Alrestatin con -15.40 kcal/mol y por último Cannabigerolic Acid con -13.27 kcal/mol Conclusiones: los resultados del docking, la interacción del ligando y la propiedades de las moléculas fueron significativamente mejores que los inhibidores de AR comerciales Alrestatin Tolrestat y Epalrestat, por lo tanto el Anthocyanin podría ser un inhibidor potente de AR.
Introduction: Hyperglycemia in diabetic patients becomes an abundant variety of complications, such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The participation of aldose reductase (AR), the main enzyme in the metabolic pathway of polyols, is involved in their progression. Considering the relevant results found in bibliographic reviews about the toxic potential of synthetic molecules used for the inhibition of RA in patients, this article proposes an alternative for the identification in silico of natural inhibitory molecules of RA that present a possible reduction of toxicity and adverse effects in patients. Methods: Initially, phytochemicals (ligands) with hypoglycemic, anti-inflammatory and antioxidant characteristics were searched; later, the database had a library of a total of 47 molecules, of which 26 are phytochemicals not reported, 17 reported natural and 4 Synthetic reports were then processed together with the protein in AutoDock Tools and the coupling was carried out in AutoDock Viña, finally the best of each group were DM in the Amber18 software. Results: From Docking: the best phytochemicals was Anthocyanins with an affinity for RA of -10.1 kcal / mol, the best natural reported was Cannabigerolic Acid with an affinity for RA of -8.2 kcal / mol and the best the synthetics reported was Alrestatin has an affinity for AR of -7.6 kcal / mol. From DM: the best of the 3 ligands studied is anthocyanins with an energy of -33.30 kcal / mol, followed by Alrestatin with -15.40 kcal / mol and finally Cannabigerolic Acid with -13.27 kcal / mol Conclusions: the results of the coupling, the interaction of the ligand and the properties of the molecules were significantly better than the commercial AR inhibitors Alrestatin Tolrestat and Epalrestat, therefore Anthocyanin could be a potent inhibitor of AR.
Introduction: Hyperglycemia in diabetic patients becomes an abundant variety of complications, such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The participation of aldose reductase (AR), the main enzyme in the metabolic pathway of polyols, is involved in their progression. Considering the relevant results found in bibliographic reviews about the toxic potential of synthetic molecules used for the inhibition of RA in patients, this article proposes an alternative for the identification in silico of natural inhibitory molecules of RA that present a possible reduction of toxicity and adverse effects in patients. Methods: Initially, phytochemicals (ligands) with hypoglycemic, anti-inflammatory and antioxidant characteristics were searched; later, the database had a library of a total of 47 molecules, of which 26 are phytochemicals not reported, 17 reported natural and 4 Synthetic reports were then processed together with the protein in AutoDock Tools and the coupling was carried out in AutoDock Viña, finally the best of each group were DM in the Amber18 software. Results: From Docking: the best phytochemicals was Anthocyanins with an affinity for RA of -10.1 kcal / mol, the best natural reported was Cannabigerolic Acid with an affinity for RA of -8.2 kcal / mol and the best the synthetics reported was Alrestatin has an affinity for AR of -7.6 kcal / mol. From DM: the best of the 3 ligands studied is anthocyanins with an energy of -33.30 kcal / mol, followed by Alrestatin with -15.40 kcal / mol and finally Cannabigerolic Acid with -13.27 kcal / mol Conclusions: the results of the coupling, the interaction of the ligand and the properties of the molecules were significantly better than the commercial AR inhibitors Alrestatin Tolrestat and Epalrestat, therefore Anthocyanin could be a potent inhibitor of AR.
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Palabras clave
Diabetes mellitus, Acoplamiento molecular, Aldosa reductasa, Inhidores, Dinámica molecular, Diabetes mellitus, Molecular coupling, Aldose reductase, Inhibitors, Molecular dynamics
