Molecular Docking Study of α-, β-, and γ-Mangostin from Mangosteen (Garcinia mangostana L.) Targeting VEGFR-2 and NRP-1 for Anti-Angiogenic Therapeutics in Retinopathy Diabetic

Abstract

To enhance the effectiveness of treatment in diabetic retinopathy patients, the development of drugs that have a combined effect of inhibiting Vascular Endothelial Growth Factor-2 (VEGFR-2) and Neuropilin-1 (NRP-1) should be conducted. This work simulates the interaction of α-mangostin, β-mangostin, and γ-mangostin (Garcinia mangostana L.) as a receptor against VEGFR-2 and NRP-1 as a ligand through the molecular docking approach. Redocking between receptor and native ligand (VEGFR-2, PDB ID: 4ASD and NRP-1 PDB ID: 5C7G) was performed using MGLTools 1.5.7 and Autodock Vina, then continued with PyMol2 to assure RMSD value of 0.981 Å for VEGFR-2 and 1.994 Å for NRP-1 (< 2 Å). The docking results showed that α-mangostin had the lowest binding energy to VEGFR-2 (-8.9 kcal/mol) and NRP-1 (-6.9 kcal/mol), followed by γ-mangostin with binding energy of -8.6 kcal/mol to VEGFR-2 and -6.9 kcal/mol to NRP-1, and β-mangostin with binding energy of -8.3 kcal/mol to VEGFR-2 and -6.5 kcal/mol to NRP-1. In comparison, the positive control, Sunitinib, showed binding energy of -7.9 kcal/mol to VEGFR-2 and -6.2 kcal/mol to NRP-1. This indicates that these compounds have a more lowest energy binding to VEGFR-2 and NRP-1 than Sunitinib. In addition, the docking results visualized using Biovia Discovery Studio 2021 showed that these compounds have hydrogen bonds and several other bonds to the active sites of VEGFR-2 and NRP-1. Hence, the proposed compounds have the potential to be further synthesized and evaluated in vitro and in vivo as a pathological anti-angiogenesis drug in diabetic retinopathy.