Computational modeling, synthesis and enzymatic assay of terpenoid, phenol, and benzaldehyde derivatives as tyrosinase inhibitors

Tyrosinase is the rate-limiting enzyme in the production of melanin, which is responsible for skin pigmentation. Overactivity of tyrosinase can lead to increased melanin synthesis, which causes skin hyperpigmentation, among other things. Examining the interaction between various inhibitors and tyrosinase can enhance our comprehension of how these inhibitors can be effectively employed to hinder both melanogenesis and enzymatic browning. Molecular docking investigations offer insights into the strength of binding between the inhibitor and the enzyme, the identification of enzymatic binding sites, and the affinity of different functional groups. The computational research primarily explores potential binding sites and different functional groups as inhibitors of tyrosinase, determination of their inhibition constants, assessment of the binding energies associated with each site, and analysis of the intermolecular interactions specific to each inhibitor-binding site pair. AutoDock software was utilized in this study to pinpoint binding sites and evaluate the intermolecular interactions between the inhibitors and tyrosinase. Once potential inhibitors were identified, molecules were either obtained commercially or synthesized in the lab. After synthesis of compounds was complete, an inhibition assay was performed to identify which compounds exhibited an inhibitory effect on the enzyme. Results were compared and contrasted to the computational data.