Synthesis of Arylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one) Derivatives and Their Effect on Tyrosinase Activity

The objective of this study was to test the inhibitory effect of five newly synthesized arylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one) derivatives. The structural characterization and stereochemistry of synthesized compounds were deduced from analyses of experimental FT-IR, 1H, 13C NMR spectra and theoretical methodology of DFT study based on the global chemical reactivity indices calculated using the 6-31G** level of theory. To predict the stability of the newly synthesized compounds, the reactivity descriptors obtained at B3LYP level (Egap, dipole moment, μ, η, ω) were computed. The docking study and the selected quantum chemical descriptors computed for compounds 1−5 exhibit a good agreement. The strongest inhibitors showed 25 to 30 % inhibition of tyrosinase activity. Results were supported by docking studies of the binding of the strongest inhibitors to the enzyme. The results suggest that tetraketones of this type, due to their tyrosinase inhibitory effect, represent potential agents in the treatment of various types of melanomas and skin hyperpigmentation