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

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 H3PMo12O40 and two transition metal‐substituted Keggin‐type polyoxometalates (Na7PMo11CoO40 and Na7PMo11ZnO40) on tyrosinase were studied by kinetics and molecular modeling. Kinetic studies indicated that all compounds had more potent inhibitory activities than standard arbutin, and H3PMo12O40 (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.

Polyoxometalates as Potential Next‐Generation Metallodrugs in the melanogenesis inhibitor

“…First, the three‐dimensional structure of a series of POMs is generated through the construction tools in MOE. Then, after removing the water molecules, use the default parameters of MOE (gradient: 0.05, force field: MMFF94X) to perform 3D protonation and energy minimization (energy convergence is 0.001 kcal/mol), [37] and finally use the Site Finder determines the active site of the protein, and the default parameters for docking are Placement: Triangle Matcher, Rescoring 1: London dG, Refinement: Forcefield, Rescoring 2: London dG [20] . After docking, use pymol software for visual analysis.…”

“…protein, and the default parameters for docking are Placement: Triangle Matcher, Rescoring 1: London dG, Refinement: Forcefield, Rescoring 2: London dG. [20] After docking, use pymol software for visual analysis. The tyrosinase used in the docking is derived from the 3D homologous crystal model of Agaricus bisporus tyrosinase (PDB ID: 2Y9W) in the RCSB protein database.…”

“…[7,8] Because tyrosinase catalyzes the rate-limiting step of melanin synthesis, tyrosinase inhibitors are highly valued by the pharmaceutical, cosmetic and food industries. [15,16] However, the current commercial tyrosinase inhibitors are not completely satisfactory, [17,18] hydroquinone and kojic acid can cause skin irritation, [15,19] and arbutin has potential cytotoxicity, [20] so the design of tyrosinase inhibitors low cytotoxicity, high efficiency, and cheap tyrosine inhibitors is particularly attractive targets in areas such as cosmeceuticals and food.…”

Research progress on the inhibition of enzymes by polyoxometalates

“…The most typical commercial tyrosinase inhibitors are Kojic acid and arbutin, but they have potential toxicity to cell and cause dermal sensitization at therapeutic concentrations. 36 Because the extraction process from natural substances is complicated and the extraction rate is low, the synthetic compounds are simple and fast to operate and the yield is high. POMs have the characteristics of structural diversity, adjustable charge variability, high stability, non-toxicity, nonvolatility and strong electron acceptance, it is possible for site recognition, molecular recognition, molecular interaction and so on.…”

Oxidative Desulfurization of Liquid Fuels Using Polyoxometalate-Based Catalysts: A Review

“…POMs are known as transition metal-oxygen cluster anions with a three-dimensional structure . POMs have been applied in catalysis, medicine, biology, material science, electron-transfer processes, and nanochemistry. − …”