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Medicinal Chemistry Research

, Volume 28, Issue 1, pp 95–103 | Cite as

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

  • Sultan Ullah
  • Jinia Akter
  • Su J. Kim
  • Jungho Yang
  • Yujin Park
  • Pusoon ChunEmail author
  • Hyung R. MoonEmail author
Original Research
  • 61 Downloads

Abstract

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.

Keywords

Tyrosinase inhibitor (E)-β-phenyl-α,β-unsaturated carbonyl 2-phenyl-1 4-naphthoquinone HMBC Docking simulation 

Notes

Acknowledgements

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2267_MOESM1_ESM.docx (7.6 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of PharmacyPusan National UniversityBusanSouth Korea
  2. 2.College of Pharmacy and Inje Institute of Pharmaceutical Sciences and ResearchInje UniversityGimhaeSouth Korea

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