<![CDATA[High-risk neuroblastoma (HR-NB) is an aggressive form of childhood cancer with a five-year survival rate of less than 50%, underscoring the need for more efficacious and less toxic treatments. The glycoprotein vitronectin (VN) has been linked to poor prognosis in patients with HR-NB, thus inhibitors of VN function represent a promising avenue for molecular mechanotherapy. This study investigated the binding affinity between the somatomedin B (SMB) domain of VN and natural compounds from the medicinal plant, Olax subscorpioidea, targeting the plasminogen activator inhibitor-1 (PAI-1). The therapeutic potential of α-amyrin (AMY), lupeol (LUP), and olax chalcone A (olax CHA) was tested in combination with an integrin antagonist of VN, cilengitide (CLG), using the SK-N-BE(2) HR-NB cell line as a model. Molecular docking studies indicated protein-ligand interactions for all compounds, with CLG showing the most favorable binding free energy, followed by LUP, AMY, and olax CHA. Molecular dynamics simulations indicated the SMB domain of VN binding site of PAI-1 initially exhibited flexibility, with alpha-carbon root mean square deviation (RMSD) stabilizing at 1.8-2.1 Å. All compounds reduced SK-N-BE(2) cell viability in a dose-dependent manner. CLG showed the strongest antiproliferative effect (IC₅₀ = 15.25 µM). Olax CHA had higher efficacy than AMY and LUP (IC₅₀ = 74.23 µM vs. 125.45 µM and 103.36 µM). Combining the compounds with CLG further decreased viability and IC₅₀ values. Synergy analysis showed only olax CHA plus CLG had a synergistic effect. This suggests olax CHA plus CLG as a promising therapeutic strategy against neuroblastoma cells.]]>
