Evaluation of thiazolidinone derivatives as a new class of mushroom tyrosinase inhibitors

Tyrosinase (EC 1.14.18.1) is a key copper-containing metalloenzyme widely distributed in nature and plays determinant role in melanin biosynthesis. The enzyme manifests two unusual catalytic properties including oxidase and monooxygenase activities. Its inhibitors may be applied to efficiently treat of hyper-pigmentation and widely used in pharmaceutical and cosmetic products, as well as food supplements and insecticides. The present study aims to evaluate the inhibitory effects of some novel azo-hydrazone tautomeric dyes (4a-e) including bioactive thiazolidinone moiety on the activity of the mushroom tyrosinase. When L-3,4-dihydroxyphenylalanine (L-Dopa) was used as the substrate for the enzyme, the compounds 4d, 4a, and 4e showed strong inhibitory effects against the activity of the enzyme (61%, 56%, and 49% inhibition in the presence of 60 mu M of each compound, respectively). The IC50 values of the synthetized compounds were measured and their inhibition properties were also visualized by zymography. According to tyrosinase inhibitory activity, the compounds 4a, 4c, 4d and 4e exhibited strong inhibitory activities with IC50 values of 45.83,140.25,37.59, and 42.31 mu M, respectively, compared to the positive control kojic acid (29.44 mu M). Kinetic study of 4d compound (as the most potent inhibitor) revealed that the compound acts as a reversible competitive inhibitor of the enzyme with the Ki value of 31.0 mu M. We also simulated the molecular docking with the compound 4d and the results confirmed that the compound strongly interacts with the mushroom tyrosinase residues. All results totally suggest that thiazolidine derivatives, especially 4d, 4a, and 4e, can be considered as safe and efficient tyrosinase inhibitors. They also have the potential to be used in the correspond fields. (C) 2017 Elsevier B.V. All rights reserved.