Design and evaluation of Ugi-derived peptoids as antibacterial and anticancer agents: experimental and computational insights.

PURPOSE OF OBJECTIVE: Novel heterocyclic analogs with dual antibacterial and anticancer potential were synthesized to address the limitations posed by multidrug resistance and current therapies. MATERIALS AND METHODS: A series of N-heterocyclic peptoids was synthesized using the Ugi-multicomponent reaction. The obtained derivatives were evaluated for their antibacterial activity toward S. aureus and E. coli, as well as for their anticancer potential against A549 lung adenocarcinoma cells. Cytotoxic effects on Vero cells were also assessed. Furthermore, molecular docking and molecular dynamics simulations were performed to investigate the binding affinities and interaction stabilities of the compounds with target proteins. RESULTS: Compound 5d exhibited pronounced antibacterial activity against both bacterial strains. Furthermore, compounds 5k and 5l showed significant anticancer efficacy with minimal cytotoxic effects on normal cells. Molecular docking studies indicated strong binding affinities for compounds 5a, 5d and 5l, while molecular dynamics simulations confirmed the stability of the corresponding ligand-protein interactions. CONCLUSIONS: The Ugi-derived peptoids exhibited potent antibacterial and anticancer activities, suggesting that their structural framework offers valuable insights for future structure-activity relationship studies and the design of novel therapeutic derivatives.