Molecular Docking Study of Benzimidazole Derivatives as Macromolecular TYRP1 Inhibitors in Melanoma

ABSTRACT

A series of benzimidazole derivatives ( Y1–Y3 ) were synthesized and structurally characterized using FTIR and ¹ H‐NMR spectroscopy. Their binding potential toward tyrosinase‐related protein 1 (TYRP1) was evaluated using molecular docking analysis. Among the investigated compounds, Y2 exhibited the highest binding affinity (−7.10 kcal/mol), forming stable interactions with key active‐site residues, including LEU460, GLN236, and GLY116. In contrast, Y1 and Y3 showed moderate binding affinities (−5.65 and −5.89 kcal/mol, respectively). The enhanced performance of Y2 is attributed to the presence of an acyl functional group, which improves hydrogen bonding and electrostatic interactions within the binding site. These findings demonstrate the importance of structural modification in optimizing ligand‐macromolecular interactions and highlight benzimidazole derivatives as promising candidates for TYRP1 inhibition in melanoma‐related applications.