A Molecular Docking Comparison Between Chalcones and Macromolecule Natural Products
Nuaman F. Alheety, Mudhir Abed Ali, Mustafa A. Alheety, Bilal J. M. Aldahham, Farah En‐nakra Hendy, Jalal Abdulkareem Abbas, Muhammed J. JasemABSTRACT
Chalcone derivatives are widely recognized as versatile scaffolds in medicinal chemistry with promising anti‐inflammatory potential. In this study, two chalcone derivatives (K1 and K2) bearing amino and nitro substituents were synthesized and structurally characterized using FTIR, 1 H‐NMR, 1 3 C‐NMR, and LC–MS/MS techniques. Their binding interactions were evaluated via molecular docking against three key inflammatory protein targets: COX‐2, IKKβ, and NF‐κB, in comparison with selected natural bioactive compounds. The docking results revealed that K1 and K2 exhibit strong binding affinity, particularly toward NF‐κB (−7.62 and −7.83 kcal/mol), surpassing most reference compounds and approaching curcumin. Key interactions with residues such as Arg415 and Arg179 indicate stable binding within functional regions. These findings highlight the potential of synthetic chalcones as promising lead compounds and provide a molecular framework linking natural bioactives with modern drug design.