Mechanism of melanogenesis inhibition by Keggin-type polyoxometalates

Abnormal melanin overproduction can result in hyperpigmentation syndrome in human skin diseases and enzymatic browning of fruits and vegetables. Recently, our group found that Keggin-type polyoxometalates (POMs) can efficiently inhibit tyrosinase activity. However, it remains unclear whether Keggin-type POMs exhibit optimal effects in vivo. Additionally, the inhibitory effect and mechanism of action of POMs on cellular tyrosinase activity and melanogenesis have been rarely reported. Here we demonstrate that our screened and synthesised PMo11Zn and GaMo12 show superior inhibitory effects on melanin formation as well as inhibition of cellular tyrosinase activity compared to other Keggin-type POMs. Intriguingly, we reveal that Keggin-type POMs competitively bind to tyrosinase mainly through more interactions with Cu2+ ions and the amino acid residue is capable of forming van der Waals, cation-& pi; and hydrogen bonds, resulting in a reversible non-covalent complex formation. Our findings provide valuable insights into the design, synthesis and screening of polyoxometalates as multifunctional metallodrugs and food preservatives against hyperpigmentation.

Automated summary

We found that Keggin-type polyoxometalates (POMs) can efficiently inhibit tyrosinase activity and have superior inhibitory effects on melanin formation and cellular tyrosinase activity compared to other Keggin-type POMs. Our study also reveals that Keggin-type POMs bind competitively to tyrosinase through interactions with Cu2+ ions and amino acid residues, resulting in a reversible non-covalent complex formation. These findings provide valuable insights into the design, synthesis, and screening of polyoxometalates as multifunctional metallodrugs and food preservatives against hyperpigmentation.