Tyrosinase is a key
enzyme in
melanin synthesis, catalyzing the initial rate-limiting steps of
melanin synthesis. Abnormal and excessive
melanin synthesis is the primary cause of serious skin disorders including
melasma, senile
lentigo,
freckles, and age spots. In attempts to find potent and safe
tyrosinase inhibitors, we designed and synthesized a novel compound, (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one (MHY1498), and evaluated its
tyrosinase inhibitory activity in vitro and in silico. The chemical structures of (Z)-3-benzylidenethiochroman-4-one analogues, including the novel compound MHY1498, were rationally designed and synthesized as hybrid structures of reported potent
tyrosinase inhibitors, which were confirmed both in vitro and in vivo: (Z)-5-(substituted benzylidene)thiazolidine-2,4-diones (Compound A) and 2-(substituted phenyl)benzo[d]
thiazoles (Compound B). During screening, MHY1498 showed a strong dose-dependent inhibitory effect on mushroom
tyrosinase. The IC50 value of MHY1498 (4.1 ± 0.6 μM) was significantly lower than that of the positive control,
kojic acid (22.0 ± 4.7 μM). In silico molecular multi-docking simulation and inhibition mechanism studies indicated that MHY1498 interacts competitively with the
tyrosinase enzyme, with greater affinity for the active site of
tyrosinase than the positive control. Furthermore, in B16F10
melanoma cells treated with α-
melanocyte-stimulating hormone, MHY1498 suppressed both
melanin production and
tyrosinase activity. In conclusion, our data demonstrate that MHY1498, a synthesized novel compound, effectively inhibits
tyrosinase activity and has potential for treating
hyperpigmentation and related disorders.