Isolation and Evaluation of 8-Deoxygartanin from Garcinia mangostana as Dual EGFR/VEGFR-2 Inhibitors: Integrated In Vitro and Molecular Dynamics Approaches
نویسندگان
1 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
2 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
3 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
4 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
5 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
6 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
7 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, Indonesia
8 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
9 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
doi
10.48309/ajca.2026.563858.1992چکیده
Despite advances in cancer therapy, severe side effects and drug resistance highlight the need for safer multi-target strategies. Targeting multiple receptor tyrosine kinases has emerged as a rational approach, and natural products, particularly xanthones from Garcinia mangostana, offer structurally diverse scaffolds with promising anticancer potential. This study presents an in vitro evaluation of three xanthones: 8-deoxygartanin (1), gartanin (2), and garcinone B (3) evaluated against epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2/KDR). Among the tested compounds, 8-deoxygartanin (1) exhibited the strongest dual inhibitory activity, with 78% and 51% inhibition of VEGFR-2 and EGFR, respectively, at 10 µM. Molecular docking analysis indicated that compound (1) binds to the active pockets of both kinases primarily through hydrophobic interactions. Furthermore, molecular dynamics simulations confirmed the stability of compound (1)-protein complexes over 500 ns in an aqueous environment. Structure-activity relationship (SAR) analysis revealed that prenylation and the specific distribution of hydroxyl and methoxy groups significantly influenced potency and selectivity. Comparison with mangostin-type analogues further underscored the superior profile of compound (1). This study provides novel mechanistic insights into Garcinia-derived xanthones and highlights 8-deoxygartanin as a promising scaffold for the rational design of dual EGFR/KDR-targeting anticancer agents.
