Discovery of Tyrosinase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation

Tyrosinase (EC 1.14.18.1) plays an indispensable role in the rate-limiting steps of melanin biosynthesis, and its uncontrolled activity may result various diseases, such as albinism, melanoma, freckles, etc. The inhibition tyrosinase provide a useful efficient strategy to treat hyperpigmentation disorders. However, widely used inhibitors, like ?-arbutin, hydroquinone, kojic acid, have many shortcomings, lower efficacy much more side effects. Herein, we reported use homology modeling multistep structure-based virtual screening for discovery novel inhibitors. In this study, 10 initial potential hits (compounds T1–T10) were evaluated enzyme kinetic with acid being control. Among them, IC50 values both T1 (11.56 ± 0.98 µmol/L) T5 (18.36 0.82 superior that (23.12 1.26 µmol/L). Moreover, also identified effective noncompetitive inhibitors by subsequent study. Above all, represent promising drug candidates therapy pharmaceutical fields, well whitening agents cosmetic applications.