Molecular docking and experimental evaluation of natural alkaloids from Chilean flora (Cryptocarya alba, Peumus boldus, and Laurelia sempervirens) for tyrosinase inhibition and depigmenting potential

Background: are sources of aporphine and benzylisoquinoline alkaloids, known for their antioxidant activity. Boldine derivatives, notably diacetylboldine (DAB, Lumiskin™), demonstrate commercial depigmenting efficacy, yet structure-activity relationship data are limited.​. Purpose: mushroom enzyme assays, molecular docking, human melanocyte (HEMn-DP), and 3D epidermal (MelanoDerm™) models to elucidate depigmenting mechanisms. Material and Methods: < 0.05). Results and Discussion: < 0.05; ∼arbutin), BOL (-10%), and DAB/LTS inactivity, highlighting the superiority of C-3 halogenation. Conclusion: LTS is the premier natural inhibitor; optimization of 3BrBOL validates BOL derivatization for ARB equivalent depigmentation in 3D models. These findings support the development of hydroquinone-free cosmeceuticals from Chilean flora alkaloids and advocate the use of nanoemulsions to enhance delivery and reduce cytotoxicity.