Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid


J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 929-942, Sep-Oct 2024. DOI: Original Article Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid contained in Peperomia pellucida (L.) Kunth against various diabetes mellitus receptors [Estudios de acoplamiento y dinámica molecular del ácido 8,9-dimetoxielágico contenido en Peperomia pellucida (L.) Kunth frente a varios receptores … Continue reading Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 929-942, Sep-Oct 2024.


Original Article

Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid contained in Peperomia pellucida (L.) Kunth against various diabetes mellitus receptors

[Estudios de acoplamiento y dinámica molecular del ácido 8,9-dimetoxielágico contenido en Peperomia pellucida (L.) Kunth frente a varios receptores de diabetes mellitus]

Yasmiwar Susilawati1,2, Raden Bayu Indradi2, Aiyi Asnawi3, Ellin Febrina4*

1Herbal Study Center, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia.

2Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia.

3Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung 40617, Indonesia.

4Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor 45363, Indonesia.



Context: The search for antidiabetic drugs that target the receptors involved in diabetes has received significant attention in recent years. Peperomia pellucida (L.) Kunth's ethanol extract and ethyl acetate fraction have antihyperglycemic activity. 8,9-dimethoxy ellagic acid (DEA) has shown significant diabetes mellitus activity in mice, but its interaction with diabetes receptors remains unknown.

Aims: To perform molecular docking and molecular dynamics simulations to explore the binding interactions and stability of DEA within the binding sites of enzymes involved in diabetes.

Methods: At the outset, the utilization of molecular docking was limited to forecasting the DEA's binding orientations and affinities within the active sites of the enzymes implicated in diabetes. Following this, molecular dynamics simulation was employed to investigate the interactions, stability, and dynamic behavior of these complexes over a period of 100 nanoseconds.

Results: Molecular docking results revealed that DEA interacts with all selected receptors involved in diabetes and interacts more strongly with the aldose reductase receptor (PDB ID 3S3G) than the native ligand, with a binding energy of -10.3 kcal/mol. However, further molecular dynamics simulations confirmed the stability of the receptor complex with DEA over 100 ns, which is less potent than that of the native ligand. This is probably due to the rigidity of the DEA molecular structure.

Conclusions: This study highlights the potential of DEA derived from P. pellucida as an inhibitor of various receptors involved in diabetes.

Keywords: 8,9-dimethoxy ellagic acid; antidiabetic; in silico; Peperomia pellucida.

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Contexto: La búsqueda de fármacos antidiabéticos que se dirijan a los receptores implicados en la diabetes ha recibido mucha atención en los últimos años. El extracto etanólico de Peperomia pellucida (L.) Kunth y la fracción de acetato de etilo tienen actividad antihiperglucemiante. El ácido 8,9-dimetoxielágico (DEA) ha mostrado una actividad significativa en la diabetes mellitus en ratones, pero su interacción con los receptores de la diabetes sigue siendo desconocida.

Objetivos: Realizar simulaciones de dinámica molecular y acoplamiento molecular para explorar las interacciones de unión y la estabilidad de la DEA dentro de los sitios de unión de las enzimas involucradas en la diabetes.

Métodos: Al principio, la utilización del acoplamiento molecular se limitaba a pronosticar las orientaciones y afinidades de unión de la DEA dentro de los sitios activos de las enzimas implicadas en la diabetes. A continuación, se empleó simulación de dinámica molecular para investigar las interacciones, la estabilidad y el comportamiento dinámico de estos complejos durante un período de 100 nanosegundos.

Resultados: Los resultados del acoplamiento molecular revelaron que la DEA interactúa con todos los receptores seleccionados implicados en la diabetes e interactúa más fuertemente con el receptor de aldosa reductasa (PDB ID 3S3G) que el ligando nativo, con una energía de unión de -10,3 kcal/mol. Sin embargo, otras simulaciones de dinámica molecular confirmaron la estabilidad del complejo del receptor con DEA durante 100 ns, que es menos potente que el del ligando nativo. Probablemente esto se deba a la rigidez de la estructura molecular de la DEA.

Conclusiones: Este estudio destaca el potencial de la DEA derivada de P. pellucida como inhibidor de diversos receptores implicados en la diabetes.

Palabras Clave: ácido 8,9-dimetoxi elágico; antidiabético; in silico; Peperomia pelucida.

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Citation Format: Susilawati Y, Indradi RB, Asnawi A, Febrina E (2024) Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid contained in Peperomia pellucida (L.) Kunth against various diabetes mellitus receptors. J Pharm Pharmacogn Res 12(5): 929–942.

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