Anti-melanogenesis of novel kojic acid derivatives in B16F10 cells and zebrafish.

Novel kojic acid derivatives (KADs) with the potential ability to inhibit tyrosinase were synthesized and were further identified by Q-Exactive, IR and NMR. Among these compounds, KAD2 showed the best inhibitory effects on diphenolase activity and monophenolase activity, with IC50 of 7.50 µM and 20.51 µM, respectively. The anti-melanogenic activity of KAD2 was further confirmed by assessing the inhibition of melanin content and intracellular tyrosinase activity in B16F10 cells and zebrafish model. It demonstrated that KAD2 suppressed the expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase related protein-1 and 2 (TRP-1 and TRP-2) in a concentration-dependent manner. Furthermore, KAD2 dose-dependently suppressed the expression of the phosphorylation of protein kinase A (PKA) and cAMP-response element binding protein (CREB) and rescued the phosphorylation of Akt. Additionally, KAD2 could inhibit body pigmentation in zebrafish. Taken together, our findings elucidated that KAD2 has significant anti-melanogenic activity via CREB and Akt pathway-mediated suppression the expression of MITF and TYR family proteins in B16F10 cells. It could provide new insight into the development of novel anti-melanogenic agents to apply in the fields of food sciences, agriculture, cosmetics and medicine.