ABSTRACT
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.
