Insights from Multi-Target Molecular Docking and A549–BEAS-2B Comparative Assays: Valyltryptophan Dipeptide

Cancer, one of the leading causes of death worldwide, continues to be one of the most important areas where scientists are working to develop treatments. In particular, targeting dysregulated signaling pathways is seen as a key strategy for developing effective anticancer treatments. In this study, a combined in silico and in vitro approach was employed to assess the anticancer potential of Valyltryptophan (VW) dipeptide. Molecular docking analyses were conducted with five important proteins involved in oncogenic signaling—EGFR, HER2, mTOR, Akt1, and PI3K—to predict their binding modes and docking scores. Among all targets, the most favorable predicted docking score was obtained for Akt1 (–8.5 kcal/mol), with hydrogen bonding and hydrophobic contacts within the binding pocket. To complement the computational analysis, MTT assays were performed using human lung carcinoma cells (A549) and normal bronchial epithelial cells (BEAS-2B). VW reduced the MTT-derived metabolic viability of A549 cells to 51.9% of control at the highest tested concentration (1 mg/mL, 3.30 mM) after 48 h; because the 50% threshold was not crossed and the concentration–response relationship was non-monotonic, the IC50 is reported as >1 mg/mL. BEAS-2B viability remained above 70% at all tested concentrations. Two-way ANOVA indicated a significant cell type × concentration interaction (p<0.0001), although the difference between the two cell lines depended on concentration and exposure time. Overall, these results are preliminary and hypothesis-generating; they identify VW as a candidate with predicted multi-target binding potential that warrants evaluation with orthogonal viability, mechanistic, and in vivo studies