Inulavosin and its benzo-derivatives, melanogenesis inhibitors, target the copper loading mechanism to the active site of tyrosinase

摘要: Summary Tyrosinase, a melanosomal membrane protein containing copper, is key enzyme for melanin synthesis in melanocytes. Inulavosin inhibits melanogenesis by enhancing degradation of tyrosinase lysosomes. However, the mechanism which inulavosin redirects to lysosomes yet unknown. The analyses structure–activity relationship and its benzo-derivatives reveal that hydroxyl methyl groups play critical role their inhibitory activity. Intriguingly, docking studies suggest compounds showing activity bind through hydrophobic interactions cavity below copper-binding sites are located. This proposed be required association with chaperon assists copper loading Streptomyces antibioticus. benzoderivatives may compete result lysosomal mistargeting apo-tyrosinase has conformational defect.