Bioactive compounds of Plukenetia volubilis L. as c-Met tyrosine kinase ınhibitors for gastric anticancer: in silico study

Abstract

Gastric cancer remains one of the most aggressive malignancies worldwide due to its high incidence and mortality rates. Although tyrosine kinase inhibitors have demonstrated therapeutic efficacy, their use is often associated with adverse effects, highlighting the need for safer anticancer agents. Plukenetia volubilis L. is known to be rich in bioactive compounds, particularly fatty acids and phenolic compounds with natural antioxidant activity. Accordingly, this study aimed to evaluate the potential of Plukenetia volubilis L. compounds as gastric anticancer candidates through inhibition of the c-Met tyrosine kinase receptor (PDB ID: 3DKC) using an integrated in silico approach. To this end, screening drug-likeness using swissADME, molecular docking using the PyRx algorithm, molecular dynamics simulation using AMBER 22, and ADMET prediction were performed using pkCSM. Among the 28 identified compounds, ten met the drug-likeness criteria for oral drug candidates. Redocking validation using adenosine-5′-triphosphate produced a root mean square deviation value of 1.31 Å, indicating a reliable docking method. Molecular docking results show that apigenin, pinoresinol, mycophenolic acid, and oleuropein aglycone exhibit the strongest binding affinities toward c-Met tyrosine kinase, with binding free energies of −7.77, −7.57, −7.24, and −6.90 (kcal/mol), respectively. Further analysis demonstrates that apigenin forms the most stable ligand–receptor complex during molecular dynamics simulation and possesses favorable pharmacokinetic properties with no predicted hepatotoxicity based on absorption, distribution, metabolism, excretion, and toxicity analysis. In conclusion, apigenin emerges as the most promising gastric anticancer candidate from Plukenetia volubilis L. through c-Met tyrosine kinase inhibition and warrants further experimental validation.