J. Pharm. Pharmacogn. Res., vol. 12, no. 3, pp. 423-438, May-Jun 2024.
DOI: https://doi.org/10.56499/jppres23.1827_12.3.423
Original Article
Synthesis and computational study of metal complex of α-mangostin as an anticancer candidate
[Síntesis y estudio computacional de un complejo metálico de α-mangostin como un candidato anticancerígeno]
Richa Mardianingrum1, Srie Rezeki Nur Endah1, Isti Daruwati2,3, Muchtaridi Muchtaridi3,4, Ruswanto Ruswanto5*
1Pharmacy Program, Faculty of Health Science, Universitas Perjuangan, Tasikmalaya 46115, West Java, Indonesia.
2Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency (BRIN), Jl Puspiptek - Kota Tangerang Selatan, Indonesia.
3Research Collaboration Center for Theranostic Radiopharmaceuticals, Jl Ir. Soekarno KM 21, Jatinangor 45363, Indonesia.
4Department of Pharmaceutical Analysis and Medicinal Chemistry Faculty of Pharmacy, Padjadjaran University, Jatinangor, Sumedang 45363, West Java, Indonesia.
5Pharmacy Program, Universitas Bakti Tunas Husada, Tasikmalaya 46115, West Java, Indonesia.
*E-mail: ruswanto@universitas-bth.ac.id
Abstract
Context: The number of breast cancer patients from year to year is increasing, accompanied by an increase in global mortality; the position in Indonesia has reached 60-70% with end-stage conditions. ERα antiproliferative activity exists in α-mangostin compounds, but this compound still has several physicochemical problems, including its solubility. Therefore, efforts are needed to increase the activity of α-mangostin and its affinity as an alpha estrogen receptor antagonist through a structure-based design method.
Aims: To obtain new compounds derived from α-mangostin in the form of a metal complex with cobalt (AM-Co), platinum (AM-Pt), and iron (AM-Fe) as medicinal ingredients that can be used as breast cancer therapeutic agents.
Methods: The research methods include in silico studies (pharmacokinetic and toxicity prediction, molecular docking, and molecular dynamics), semi-synthesis to form a complex compound, and testing cytotoxic activity against MCF-7 and T-47D human breast cancer cells.
Results: From the in vitro test results, it can be seen that the AM-Pt compound showed the best anticancer activity on MCF-7 cells compared to others from IC50 and SI values; this was supported by the results of in silico studies either through molecular docking or molecular dynamics, where this compound was more effective.
Conclusions: Furthermore, it can be used as an anticancer candidate; particularly, its activity is predicted to be more potent as an ERa antagonist than a-mangostin and cisplatin.
Keywords: cobalt; iron; a-mangostin; metal complex; platinum.
Resumen
Contexto: El número de pacientes con cáncer de mama aumenta de año en año, acompañado de un aumento de la mortalidad global; la situación en Indonesia ha alcanzado el 60-70% con estados terminales. ERα existe actividad antiproliferativa en los compuestos de α-mangostin, pero este compuesto sigue presentando varios problemas fisicoquímicos, entre ellos su solubilidad. Por lo tanto, es necesario esforzarse por aumentar la actividad de α-mangostin y su afinidad como antagonista del receptor alfa de estrógenos mediante un método de diseño basado en la estructura.
Objetivos: Obtener nuevos compuestos derivados de α-mangostin en forma de complejo metálico con cobalto (AM-Co), platino (AM-Pt) y hierro (AM-Fe) como ingredientes medicinales que puedan utilizarse como agentes terapéuticos del cáncer de mama.
Métodos: Los métodos de investigación incluyen estudios in silico (predicción farmacocinética y de toxicidad, acoplamiento molecular y dinámica molecular), semisíntesis para formar un compuesto complejo y ensayo de la actividad citotóxica frente a células humanas de cáncer de mama MCF-7 y T-47D.
Resultados: A partir de los resultados de las pruebas in vitro, se puede observar que el compuesto AM-Pt mostró la mejor actividad anticancerígena sobre células MCF-7 en comparación con otros a partir de los valores de IC50 y SI; esto fue apoyado por los resultados de los estudios in silico ya sea a través de docking molecular o dinámica molecular, donde este compuesto fue más eficaz.
Conclusiones: Además, puede utilizarse como candidato anticancerígeno; en particular, se prevé que su actividad sea más potente como antagonista de ERα que α-mangostin y el cisplatino.
Palabras Clave: cobalto; complejo metálico; hierro; α-mangostin; platino.
Citation Format: Mardianingrum R, Endah SRN, Daruwati I, Muchtaridi M, Ruswanto R (2024) Synthesis and computational study of metal complex of α-mangostin as an anticancer candidate. J Pharm Pharmacogn Res 12(3): 423–438. https://doi.org/10.56499/jppres23.1827_12.3.423
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