Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes

: The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cyclesof mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead tothe discovery of whitening agents, medicinal products, anti-browning substances and compounds forcontrolling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccaseinhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturallyoccurring compounds and their activity was measured by spectrophotometric and electrochemicalassays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detectthe type of protein-ligand interaction and half maximal inhibitory concentration (IC50). Most ofthe inhibitors showed an IC50 in a range of 20-423 nM for tyrosinase and 23-2619 nM for laccase.Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the newcompounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 µM. Insilico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing aprenylated chain as the lead structure, which activated strong and effective interactions at the activesite of the enzyme. These data were confirmed by in vivo experiments performed on the insect modelTenebrio molitur.