Biological evaluation of Keggin-type polyoxometalates on tyrosinase: Kinetics and molecular modeling

Abnormal overexpression of tyrosinase activity can lead to the production of hyperpigmentation in human skin and enzymatic browning in fruits and vegetables. Herein, the inhibition and mechanism of the H₃ PMo₁₂ O₄₀ and two transition metal-substituted Keggin-type polyoxometalates (Na₇ PMo₁₁ CoO₄₀ and Na₇ PMo₁₁ ZnO₄₀ ) on tyrosinase were studied by kinetics and molecular modeling. Kinetic studies indicated that all compounds had more potent inhibitory activities than standard arbutin, and H₃ PMo₁₂ O₄₀ (IC₅₀  = 0.443 ± 0.006 mm) is ~15-fold stronger inhibition than arbutin. Additionally, all compounds inhibited tyrosinase in a reversible competitive manner. Intriguingly, molecular modeling elucidated that three compounds competitively bind to tyrosinase mainly through more interactions with Cu²⁺ ions and the amino acid residue capable of forming cation-π and hydrogen bonding, forming a reversible non-covalent complex. Molecular simulation study correlated well with the biological activity of three compounds in vitro. This work provided new insights into design and synthesis of polyoxometalates as tyrosinase inhibitors in the field of medicine, cosmetic, and food.