Synthesis And Preliminary Functional Studies Of Novel Tyrosinase Modulators

Objective: The method of creating Tyrosinase(Tyr)inhibitors based on Proteolysis-Targeting Chimeras(PROTACs)is anticipated to accomplish safe and effective regulation of the protein and hence suppress melanogenesis by adopting "event-driven" drug design theory.Tyrosinase modulators could be developed in the future thanks to its ability to target the tyrosinase protein in the organism and the method of precise alteration of the tyrosinase.Methods: There are currently two efficient ways to achieve targeted and precise regulation: one is to control the expression level of target proteins at the molecular biology level,and the other is to inhibit the function of target proteins.In recent years,research has begun to focus on the first strategy,namely the regulation of post-translational target protein content by small molecule probes,which is among those strategies that are thought to be most effective.The PROTACs technique was used in this thesis to create a novel Tyr small molecule degradation agent,with kojic acid(KA)serving as the "warhead." B16 mouse melanoma cells(also known as B16 cells)were used in the tests,and it was discovered that melanin and intracellular Tyr were inhibited by the representative compound BCP-1 in B16 cells.Further research was done into the concentration and time dependence of the Tyr downregulation on protein content caused by compound BCP-1.On the other hand,it was investigated how BCP-1 affected the expression of proteins on the signaling pathways involved in melanin formation in melanoma cells.Results: It was successful to create the Tyr-targeting chemical BCP-1,which greatly decreased the amount of melanin in B16 cells and suppressed the expression of Tyr when compared to the positive control medication KA.BCP-1 might inhibit the expression of Tyr,TRP-1,TRP-2,and MITF in B16 cells in a concentration-and time-dependent manner,according to a Western blot(WB)experiment.Conclusion: According to the findings of the experiment,it was determined that BCP-1 may successfully suppress intracellular Tyr,offering a fresh perspective for the investigation of Tyr degradation agents in the future.