The tyrosinase-inhibitory effects of 2-phenyl-1,4-naphthoquinone analogs: importance of the (E)-β-phenyl-α,β-unsaturated carbonyl scaffold of an endomethylene type
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In order to investigate the effect of the (E)-β-phenyl-α,β-unsaturated carbonyl scaffold of an endomethylene type on tyrosinase inhibition, 2-phenyl-1,4-naphthoquinone derivatives were synthesized by Michael addition of substituted benzenes to 1,4-naphthoquinone and subsequently an auto-oxidation. Most of the derivatives potently inhibited mushroom tyrosinase and four derivatives, including 1c (IC50 = 22.00 ± 1.63 μM), more potently inhibited mushroom tyrosinase than kojic acid (IC50 = 37.86 ± 2.21 μM). Cell-based assays using B16F10 cells (a melanoma cell line) showed 1c dose-dependently suppressed melanin production and more potently inhibited tyrosinase activity than kojic acid. Docking simulation results between 1c and tyrosinase and a kinetic study suggest that 1c is a competitive inhibitor that binds to the active site of tyrosinase. These results support that anti-melanogenic effect of naphthoquinone derivatives results from their tyrosinase inhibiting activity and the (E)-β-phenyl-α,β-unsaturated carbonyl scaffold of an endomethylene type can confer tyrosinase-inhibitory activity.
KeywordsTyrosinase inhibitor (E)-β-phenyl-α,β-unsaturated carbonyl 2-phenyl-1 4-naphthoquinone HMBC Docking simulation
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education (NRF-2017R1D1A1B03027888).
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Conflict of interest
The authors declare that they have no conflict of interest.
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