Complex Inhibition of Tyrosinase by Thiol-Composed Cu²⁺Chelators: A Clue for Designing Whitening Agents

Abstract

The inhibition of tyrosinase has attracted considerable attention for potential medicinal and cosmetic applications, as well as in agriculture. This study investigated the inhibition effects of thiol-associated Cu(2+) chelators and deduced a strategy for designing and/or selecting tyrosinase inhibitors. Among the several compounds tested, dithioglycerine (DTGC) was selected for further experiments on the inhibition kinetics on tyrosinase. Different types of tyrosinases derived from mushroom and from the transient overexpression in HEK293 cells were tested individually. The results showed that DTGC significantly inhibited human tyrosinase in a complex manner (slope-parabolic mixed-type inhibition), which was comparable to mushroom tyrosinase. The affinity of DTGC affinity to human tyrosinase was evaluated by setting up a K(i slope) equation. The results suggest that a Cu(2+) chelator modified with thiol groups has potential as a whitening agent. In addition, a strategy for designing and/or selecting tyrosinase inhibitors that target the active enzyme site was also suggested.

The Effect of Trifluoroethanol on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Simulations

“…The partial conformational changes induced by TFE are likely to have affected the substrate-enzyme state of the parabolic V max changes and, simultaneously, interfered with L-DOPA docking to the active site, resulting in K m changes. Complex types of inhibition of tyrosinase by various compounds have been observed previously [25,26,[33][34][35]. Compared to these results, however, the TFE-induced mechanism of inhibition was different in two major ways: TFE did not bind directly to the copper ions of the active site, and secondary structural changes were accompanied by tertiary structural changes that directly induced a complete loss of activity.…”

Application of ergothioneine-rich extract from an edible mushroom Flammulina velutipes for melanosis prevention in shrimp, Penaeus monodon and Litopenaeus vannamei

“…Certain compounds having thiols, such as ESH, are known to be powerful nucleophiles that can chelate Zn 2+ and Cu 2+ (Park, Lyou, Hahn, Hahn, & Yang, 2006). Furthermore, Hanlon (1971) reported that, of the 4 copper enzyme systems under study, only PPO was inhibited by ESH.…”

Biochemical intervention of ergothioneine-rich edible mushroom (Flammulina velutipes) extract inhibits melanosis in crab (Chionoecetes japonicus)

“…In vitro experiments clearly showed that exogenous L-ESH decreased crab HLS PO activity. Certain compounds having thiol, such as ESH, are known to be powerful nucleophiles that can chelate Zn 2+ and Cu 2+ (Hanlon, 1971;Park, Lyou, Hahn, Hahn, & Yang, 2006). It has been known that PO and hemocyanin from crustaceans have oxygen-binding sites that are formed by two copper ions (Kim et al, 2002).…”