The bioactive compounds in bilimbi leaves (Averrhoa bilimbi L.) as natural-based anticancer targeting on VEGFR-2: In silico studies

Abstract

Cancer is characterized by uncontrolled cell proliferation. Over the past five years, cancer prevalence in Indonesia has risen from 1.4% to 1.49%. Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) plays a critical role in promoting tumor growth and metastasis by initiating angiogenesis, making it a promising target for anticancer agents. Averrhoa bilimbi L., a member of the Oxalidaceae family, contains secondary metabolites such as flavonoids, phenols, alkaloids, tannins, and coumarins, with its leaves reported to have antineoplastic activity, though the molecular mechanisms remain unclear. This study evaluates the activity of bioactive compounds in bilimbi leaves on VEGFR-2 through computational approaches. Drug-likeness and ADMET predictions were conducted using Mcule and PreADMET tools, followed by pharmacophore screening with LigandScout and molecular docking analysis with AutoDock. Among the 27 compounds analyzed using Lipinski’s Rule of Five, ADMET predictions, and molecular docking, 2-(1-phenylethyl)-phenol emerged as the top candidate based on the identification of the hit from pharmacophore modeling with a Gibbs free energy of -7.78 kcal/mol and an inhibition constant of 1.99 µM, as well as passing the criteria of Lipinski’s rule with a favorable pharmacokinetic profile. Furthermore, this compound demonstrated interaction with the ASP A:1046 residue in VEGFR-2, similar to the reference drug Sorafenib, highlighting its potential as an anticancer agent. Our findings suggest that bilimbi leaves and their bioactive compounds merit further exploration as VEGFR-2 inhibitors for cancer therapy.