Investigation of the Inhibitory Activity of β-Arbutin and its Analogues on Tyrosinase Based on Molecular Docking and Enzyme Inhibition Kinetics.

β-Arbutin, a natural glucoside hydroquinone derivative known for its skin-whitening properties through tyrosinase inhibition in melanin synthesis, may pose potential risks of allergy and carcinogenicity due to the release of hydroquinone during use. This study explores the inhibitory effects of phenyl-β-D-pyranoglucoside (compound 1), 4-methoxyphenyl-β-D-pyranoglucoside (compound 2), 4-hydroxymethylphenyl-β-D-pyranoglucoside (compound 3), and β-arbutin (compound 4) on tyrosinase using enzyme kinetics, molecular docking, and molecular dynamics simulations. Results show compounds 1, 3, and 4 exhibit competitive inhibition, while compound 2 shows mixed inhibition. Docking analysis reveals phenyl rings of all compounds interact with the enzyme's active site, with compound 3 forming a metal bond with copper ions. MD simulations indicate high stability for compounds 2, 3, and 4, with compound 3 showing the lowest RMSD and compact Rg, suggesting stronger binding. Compound 1 is less stable and less inhibitory. These insights are valuable for designing effective tyrosinase inhibitors.