J. Pharm. Pharmacogn. Res., vol. 14, no. 3, Article ID 2526, May-Jun 2026.
DOI: https://doi.org/10.56499/jppres_14.3.2526Original Article
A pyranonaphthoquinone from Rhinacanthus nasutus (L.) Kurz roots as a potential protein tyrosine phosphatase 1B allosteric binder: An in silico study
[Una piranonaftoquinona de las raíces de Rhinacanthus nasutus (L.) Kurz como potencial ligando alostérico de la proteína tirosina fosfatasa 1B: un estudio in silico]
Wilmar Maarisit*, Jeane Mongi, Silvana Linda Tumbel
Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Kristen Indonesia Tomohon, North Sulawesi, 95362, Indonesia.
*E-mail: wilmarmaarisit@fmipaukit.ac.id, wmaarisit@yahoo.com
Abstract
Context: Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for type 2 diabetes mellitus (DM) as it can deactivate insulin signalling.
Aims: To isolate the secondary metabolites from the roots of Rhinacanthus nasutus and assess their predicted binding affinity toward the PTP1B allosteric site using an in silico approach.
Methods: The isolated compounds were identified using spectroscopic techniques and the binding at the allosteric site of PTP1B was predicted by molecular docking. In addition, the most relevant complex was analyzed using molecular dynamics simulation and molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) binding free-energy calculation.
Results: Compound 1 was identified as 4-oxo-rhinacanthin B, along with five known analogues of rhinacanthin obtained from the roots of R. nasutus. Docking indicated that compounds 1-6 may fit into the PTP1B allosteric pocket, with compound 1 forming contacts with Asn193, Phe196 and Arg199. The compound 1–PTP1B complex remained associated with the allosteric pocket for most of the simulation period of 100 ns, although a larger deviation was observed towards the end of the trajectory. MM-PBSA suggested that compound 1 had slightly less favorable predicted binding free energy than ursolic acid, mainly because of a higher positive solvation penalty.
Conclusions: Pyranonaphthoquinones from R. nasutus showed plausible in silico accommodation within the PTP1B allosteric pocket and may serve as starting scaffolds for further optimization. However, compound 1 has not been evaluated in an enzymatic assay and should therefore be regarded as a computationally prioritized scaffold for future biochemical validation, not as a validated PTP1B inhibitor.
Keywords: molecular docking; molecular dynamics; PTP1B; pyranonaphthoquinone; Rhinacanthus nasutus.
Resumen
Contexto: La proteína tirosina fosfatasa 1B (PTP1B) es una diana terapéutica validada para la diabetes mellitus tipo 2 (DM), ya que puede desactivar la señalización de la insulina.
Objetivos: Aislar los metabolitos secundarios de las raíces de Rhinacanthus nasutus y evaluar su afinidad de unión predicha al sitio alostérico de PTP1B mediante un enfoque in silico.
Métodos: Los compuestos aislados se identificaron mediante técnicas espectroscópicas y se predijo la unión al sitio alostérico de PTP1B mediante acoplamiento molecular. Además, el complejo más relevante se analizó mediante simulación de dinámica molecular y cálculo de la energía libre de unión mecánica molecular-área superficial Poisson-Boltzmann (MM-PBSA).
Resultados: El compuesto 1 se identificó como 4-oxo-rinacantina B, junto con cinco análogos conocidos de rinacantina obtenidos de las raíces de R. nasutus. El acoplamiento molecular indicó que los compuestos 1-6 podrían encajar en el bolsillo alostérico de PTP1B, con el compuesto 1 estableciendo contactos con Asn193, Phe196 y Arg199. El complejo compuesto 1–PTP1B permaneció asociado al bolsillo alostérico durante la mayor parte del período de simulación de 100 ns, aunque se observó una mayor desviación al final de la trayectoria. El análisis MM-PBSA sugirió que el compuesto 1 tenía una energía libre de unión predicha ligeramente menos favorable que la del ácido ursólico, principalmente debido a una mayor penalización de la solvatación positiva.
Conclusiones: Las piranonaftoquinonas de R. nasutus mostraron una acomodación in silico plausible en el bolsillo alostérico de PTP1B y podrían servir como andamios iniciales para una optimización posterior. Sin embargo, el compuesto 1 no se ha evaluado en un ensayo enzimático y, por lo tanto, debe considerarse un andamio priorizado computacionalmente para una futura validación bioquímica, no como un inhibidor de PTP1B validado.
Palabras Clave: acoplamiento molecular; dinámica molecular; piranonaftoquinona; PTP1B; Rhinacanthus nasutus.
Citation Format: Maarisit M, Mongi J, Tumbel SL (2026) A pyranonaphthoquinone from Rhinacanthus nasutus (L.) Kurz roots as a potential protein tyrosine phosphatase 1B allosteric binder: An in silico study. J Pharm Pharmacogn Res 13(3): 2526. https://doi.org/10.56499/jppres_14.3.2526
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