Background: Tyrosinase is a copper-containing enzyme that involves in melanine
biosynthesis and fruits enzymatic browning pathways. Chemical inhibitors of tyrosinase could
have potential applications in cosmetics, medicine and food industry. In this study, we evaluated
6-Methoxy-3,4-dihydronaphthalenone chalcone-like derivatives as potent tyrosinase inhibitors
and radical scavengers.
Methods: A series of ten 2-arylidene-6-methoxy-3,4-dihydronaphthalenone derivatives as tyrosinase
inhibitors and potential antioxidants were designed and synthesized by aldol condensation reaction.
Furthermore, tyrosinase inhibitory activity of the compounds was evaluated and to indicate the
binding mode of some of the synthesized compounds, the molecular docking analysis was performed
using AutoDock 4.2 software. The antioxidant activity of these compounds against DPPH
radical scavenging was also investigated.
Results: Results indicated that the compound bearing 3´-ethoxy and 4´-hydroxy (P5) was found to
be potential competitive tyrosinase inhibitor with IC50 value of 6.19 ± 1.05 µM that exhibited higher
tyrosinase inhibitory activity than the positive control, kojic acid, with IC50 value of 9.28 µM.
Docking results confirmed that the active inhibitors were well accommodated in the mushroom
tyrosinase active site. Compounds P5 and P8 exhibited potential radical scavenging activities with
EC50 values of 27.02 ± 0.84 and 20.40 ± 2.36 μM, respectively.
Conclusion: Therefore, P5 could be introduced as a potent tyrosinase inhibitor with radical
scavenging activity that might be a promising compound in the field of drug discovery.