J. Pharm. Pharmacogn. Res., vol. 14, no. 2, Article ID 2472, Mar-Apr 2026.

DOI: https://doi.org/10.56499/jppres_14.2.2472

Original Article

The potential of 5-O-acylpinostrobin derivatives against progesterone and EGFR-HER2 receptors as anti-breast cancer: Docking, molecular dynamics simulations, and ADMET prediction

 

[Potencial de los derivados de 5-O-acilpinostrobina contra los receptores de progesterona y EGFR-HER2 como anticáncer de mama: acoplamiento, simulación dinámica molecular y predicción ADMET]

 

Tri Widiandani^1,2,3*, Delis Susilawati⁴, Bambang T. Purwanto^1,2, Siswandono Siswodihardjo^2,5

 

¹Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.

²Research Group of Drug Development, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.

³Inter-University Center of Excellence (IUCoE) of Health Autonomy-Drug Discovery, Universitas Airlangga, Surabaya, Indonesia.

⁴Master Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.

⁵Faculty of Pharmacy, Institut Ilmu Kesehatan Bhakti Wiyata, Kediri, Indonesia.

*E-mail: tri-w@ff.unair.ac.id

 

Abstract

Context: Breast cancer involves uncontrolled proliferation of breast tissue and remains the leading cause of cancer-related mortality in women. Progesterone receptors modulate estrogen-α receptor signaling, while EGFR-HER2 overexpression promotes cancer cell proliferation and therapy resistance. Pinostrobin, isolated from Boesenbergia pandurata, exhibits anticancer activity, and its structural modification to 5-O-acylpinostrobin derivatives may enhance potency.

Aims: To predict the potential of 5-O-acylpinostrobin derivatives against progesterone and EGFR-HER2 receptors through molecular docking, molecular dynamics simulations, and ADMET predictions.

Methods: Molecular docking was performed using MOE 2022.02, followed by 100 ns molecular dynamics simulations with AMBER 20, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were evaluated using ADMETlab.

Results: All derivatives showed stronger binding affinities than pinostrobin, with pinostrobin butyrate demonstrating the highest stability during molecular dynamics to both receptors. ADMET predictions indicated favorable pharmacokinetics, although with potential carcinogenicity.

Conclusions: These findings indicate that pinostrobin butyrate exhibits promising candidate for further preclinical development as an anti-breast cancer agent.

Keywords: 5-O-acylpinostrobin; breast cancer; EGFR-HER2; in silico; progesterone.

 

 

Resumen

Contexto: El cáncer de mama implica una proliferación descontrolada del tejido mamario y sigue siendo la principal causa de mortalidad por cáncer en las mujeres. Los receptores de progesterona modulan la señalización del receptor de estrógeno α, mientras que la sobreexpresión de EGFR-HER2 promueve la proliferación de células cancerosas y la resistencia a la terapia. La pinostrobina, aislada de Boesenbergia pandurata, exhibe actividad anticancerígena y su modificación estructural en derivados de 5-O-acilpinostrobina puede aumentar su potencia.

Objetivos: Predecir el potencial de los derivados de 5-O-acilpinostrobina contra los receptores de progesterona y EGFR-HER2 mediante acoplamiento molecular, simulaciones de dinámica molecular y predicciones ADMET.

Métodos: El acoplamiento molecular se realizó con MOE 2022.02, seguido de simulaciones de dinámica molecular de 100 ns con AMBER 20, y las propiedades de absorción, distribución, metabolismo, excreción y toxicidad (ADMET) se evaluaron con ADMETlab.

Resultados: Todos los derivados mostraron afinidades de unión más fuertes que la pinostrobina, y el butirato de pinostrobina demostró la mayor estabilidad durante la dinámica molecular para ambos receptores. Las predicciones de ADMET indicaron una farmacocinética favorable, aunque con potencial carcinógeno.

Conclusiones: Estos hallazgos indican que el butirato de pinostrobina es un candidato prometedor para un mayor desarrollo preclínico como agente contra el cáncer de mama.

Palabras Clave: 5-O-acilpinostrobina; cáncer de mama; EGFR-HER2; in silico; progesterona.

 

 

https://jppres.com/jppres/pdf/vol14/jppres_14.2.2472.pdf

Citation Format: Widiandani T, Susilawati D, Purwanto BT, Siswodihardjo S (2026) The potential of 5-O-acylpinostrobin derivatives against progesterone and EGFR-HER2 receptors as anti-breast cancer: Docking, molecular dynamic simulation, and ADMET prediction. J Pharm Pharmacogn Res 14(2): 2472. https://doi.org/10.56499/jppres_14.2.2472

 

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