In-silico study of mangosteen (Garcinia mangostana L.) pericarp phytochemicals in Proto-oncogene tyrosine-protein kinase receptor RET inhibition

Abstract

Thyroid cancer is a prevalent and dangerous cancer in Indonesia. RAI-Refractory PTC is a type of thyroid cancer, in which it can be cured with multikinase inhibitors, such as Lenvatinib. However, it came with side effects that are detrimental to regimen adherence. Current trends mention finding more selective phytochemicals to treat specific kinase receptors involved in RAI-Refractory PTC. One such source of phytochemicals is Garcinia mangostana L., which is found to treat cancer in several pathways, with one pathway involving Proto-oncogene tyrosine-protein kinase receptor RET inhibition similar to Lenvatinib. This study used molecular docking and molecular dynamics, utilizing software such as Way2drug, Protox 3.0, SwissADME, PKCSM, PyMOL, PyRx, and Discovery Studio Biovia 2025, gromacs, gmx_MMPBSA, and Xmgrace to investigate the phytochemicals. The in-silico study reveals γ-mangostin showed the highest potential for Proto-oncogene tyrosine-protein kinase receptor RET receptor inhibition, albeit having undesirable binding free energy calculation according to the gmx_MMPBSA analysis. Further investigation should be conducted on γ-mangostin and the other phytochemicals through redocking, structure editing, and in-vitro and in-vivo studies.