Macromolecular Interactions of Long‐Chain Chalcones With Monoamine Oxidase B (MAO‐B): Computational Discovery and Cost‐Effective Profiling

ABSTRACT

In this study, two chalcone derivatives bearing long alkoxy chains and distinct para‐substituted aromatic moieties were synthesized, spectroscopically characterized, and computationally evaluated. Molecular docking simulations were conducted against monoamine oxidase B (MAO‐B) to assess ligand–target interactions and to guide early‐stage compound prioritization. The docking results revealed strong binding affinities for both compounds, with Z2 exhibiting the most favorable interaction profile (binding energy up to −11.67 kcal/mol), outperforming the reference inhibitor safinamide. These computational findings were integrated with an evaluation of synthetic simplicity and experimental cost, providing a cost‐aware framework for molecular selection. The combined computational–economic approach highlights molecular docking as an effective decision‐support tool for reducing experimental uncertainty and optimizing resource allocation in early‐stage chemical research.