Abstract
A set of 12 monosubstituted acetophenone thiosemicarbazone derivatives (TSCs) were synthesized and their inhibitory properties toward tyrosinase activity were tested. Moreover, their ability to inhibit melanogenesis in the B16F10 murine melanoma cell line was studied. In order to investigate the nature of interactions between the enzyme and the inhibitors, molecular docking to the active site was performed. TSCs 5, 6, 8, and 9 revealed a half maximal inhibitory concentration (IC50) below 1 µM. Compound 6 turned out to be the most potent tyrosinase inhibitor. All investigated compounds showed reversible inhibition of competitive or mixed type. The para-substituted TSCs had higher affinity for the enzyme as compared to their ortho- and meta-analogues. All investigated compounds inhibited melanin production in B16F10 cells at the micromolar level. Molecular docking showed that the sulfur atom of the thiourea moiety penetrates the active site and interacts with copper ions. The above outcomes might be helpful in the design of new tyrosinase inhibitors in the food and cosmetic industries.
Highlights
Tyrosinase belongs to the oxidoreductase family (EC 1.14.18.1)
[20,21], we reported that acetophenone thiosemicarbazones are more potent tyrosinase inhibitors than their benzaldehyde analogues
All thiosemicarbazone derivatives (TSCs) were docked to the active site of mushroom tyrosinase (Protein Data Bank (PDB): 2Y9X) [32]
Summary
Tyrosinase belongs to the oxidoreductase family (EC 1.14.18.1). There are two copper atoms in its active site which are important for catalytic activity [1]. Melanins are pigments widely distributed in nature They derive from dopaquinone, which is formed from L-tyrosine in a reaction catalyzed by tyrosinase in the pathway called melanogenesis. Tyrosinase is responsible for the formation of dark pigment (enzymatic browning) in plant-derived foods. This process affects the shelf life of fresh products, decreasing their sensory properties [5]. There is a need ti search for and characterize new, safe, and effective tyrosinase inhibitors. Tyrosinase possesses twothat copper ions in itsions active site,thiourea which makes it[14]. In our previous papers [20,21], we reported that acetophenone thiosemicarbazones are more potent tyrosinase inhibitors than their benzaldehyde analogues.
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