Alaribe, S. C. | Search bioRxiv

bioRxiv2025

Vitronectin binding affinity and cell viability effect of novel mechanotherapy drugs for neuroblastoma

High-risk neuroblastoma (HR-NB) is an aggressive form of childhood cancer with a five-year survival rate of under 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, and thus inhibitors of its function represent a promising avenue for molecular mechanotherapy. The present study sought to investigate the binding affinity between the somatomedin B (SMB) domain of VN and natural compounds derived from medicinal plants. The therapeutic potential of -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 a potential for protein-ligand interactions for all selected compounds, of which CLG demonstrated the most favorable binding free energy (kcal/mol), followed by LUP, AMY and Olax CHA. Molecular dynamics simulations demonstrated that the SMB domain of VN initially exhibited flexibility, with alpha carbon-root mean square deviation (RMSD) stabilizing at approximately 1.8-2.1 [A]. While all compounds demonstrated a dose-dependent decrease in SK-N-BE(2) cell viability, CLG exhibited higher IC50 values. Although the combination of AMY and LUP with CLG did not result in enhanced efficacy, Olax CHA exhibited a superior antiproliferative effect with higher IC50 values than AMY and LUP, and additionally showed potential synergism with CLG, suggesting a more effective therapeutic approach. This work provides valuable insights into the potential use of mechanotherapy drugs and natural products to enhance HR-NB treatment that can be expanded in future studies centered on Olax CHA.

cancer biology↗

bioRxiv2024

INVESTIGATION OF SECONDARY METABOLITES PRESENT IN METHANOLIC AND ALKALOIDAL EXTRACTS OF HUNTERIA UMBELLATA LEAVES USING COMPUTATIONAL MOLECULAR NETWORKING TOOL

Plants have long served as a vital source of therapeutic agents in both traditional and orthodox medicine. However, with the shift in drug discovery towards laboratory synthesis, there is a decline in the exploration of natural sources for drug development. This downturn calls for return to natural drug discovery and, more importantly, towards the development of improved methods of isolating, identifying, and characterising chemical moieties obtained from plants. This study redirects attention to natural product research by employing advanced metabolomic and computational approaches to characterise the bioactive compounds of Hunteria umbellata. Metabolomic technique was employed, utilising liquid chromatography-tandem mass spectrometry (LC-MS/MS) to separate the chemical components. The isolated compounds were then identified using their mass-to-charge (m/z) ratios. Chromatograms were analysed using a computational molecular networking tool to match the m/z values to known compounds in mass spectrometry libraries. Eighteen compounds were successfully isolated from the methanolic and alkaloidal extracts, including Yohimbine, (-)-Epicatechin, Picrinine, Tubotaiwine, Quercetin-3-O-robinobioside, and Pheophorbide A. To our knowledge, this represents the first comprehensive metabolomic profiling of H. umbellata using computational molecular networking, revealing a diverse set of flavonoids and indole alkaloids. Notably, the detection of Pheophorbide A, a chlorin derivative with photodynamic therapy potential, constitutes a new report for this species and suggests unexplored therapeutic relevance. These findings provide significant insight into the bioactive components of Hunteria umbellata, supporting its traditional medicinal uses. Identifying clinically relevant compounds not only validates traditional practices but also highlights the plants potential for contributing to modern drug discovery efforts.

molecular biology↗