Targeting WEE1 Kinase with Phytochemicals from Ampelocissus thyrsiflora (Blume) Planch: An Integrated In Silico and In Vitro Study Against Human Breast Cancer Cells

Introduction Breast cancer is the second most diagnosed cancer worldwide, with WEE1 kinase recognized as a key regulator of tumor progression. Natural products, particularly plant-derived metabolites, offer promising scaffolds for the development of novel WEE1 inhibitors. Materials and Methods Ethanol extracts of Ampelocissus thyrsiflora (Blume) Planch, a North Sumatran endemic plant, were obtained via maceration and subjected to phytochemical screening, PASS prediction, and Lipinski’s Rule of Five evaluation. Molecular docking and 100 ns molecular dynamics (MD) simulations were performed to investigate ligand–protein interactions. Cytotoxicity was assessed using the MTT assay on MCF-7 breast cancer cells. Results Phytochemical analysis confirmed the presence of alkaloids, flavonoids, saponins, tannins, glycosides, and steroids. Fourteen compounds exhibited strong predicted biological activity, and thirteen fulfilled drug-likeness criteria. Based on binding affinity and interactions with key WEE1 residues, four compounds were selected for MD simulations. Three demonstrated favorable MM-PBSA binding energies and stable interactions with critical residues. The ethanol extract showed an IC 50 of 2011.25 ± 42.71 µg/mL against MCF-7 cells. Discussion The computational results highlight the potential of A. thyrsiflora metabolites as multi-target inhibitors of WEE1 kinase. Although the obtained IC 50 value is comparatively high, the result provides an important preliminary basis for subsequent investigations and potential optimization of its active constituents. Conclusion Although the ethanol extract of A. thyrsiflora exhibited a high in vitro IC50, the in silico results provide a strong rationale for further exploration of its metabolites as potential WEE1-targeted anticancer agents.