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Archives of Pharmacal Research

, Volume 38, Issue 4, pp 505–511 | Cite as

Inhibition of melanogenesis by 2-[4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy]-2-methylpropanoic acid (MHY908)

  • Min Hi Park
  • Seong Jin Kim
  • Hyoung Oh Jeong
  • Kyoung Mi Moon
  • Sujin Son
  • Dae Hyun Kim
  • Hye Rim Kim
  • Min Jo Kim
  • Hwi Young Yun
  • Pusoon Chun
  • Nam Kyung Je
  • Takako Yokozawa
  • Hyung Ryong Moon
  • Hae Young ChungEmail author
Research Article

Abstract

Tyrosinase inhibitors might have potential use in cosmetic and medicinal products for the prevention of pigmentation disorders. However, only a few inhibitors are currently used due to their cytotoxicity, and lack of selectivity and stability. In this study, we synthesized several tyrosinase inhibitors and investigated their activity. To investigate the action of 2-[4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy]-2-methylpropanoic acid (MHY908) specifically in the inhibition of melanogenesis, a mushroom tyrosinase activity assay was performed. We confirmed the inhibitory effect of MHY908 at various melanin concentrations using α-MSH-induced melanoma cells. Our results indicate that MHY908 potently inhibited mushroom tyrosinase activity (IC50 = 8.19 μM) in a dose-dependent manner. Through a docking simulation, we also analyzed its binding mode to inhibit tyrosinase activity. MHY908 also decreased melanin synthesis without inducing cytotoxicity. These results suggest that MHY908 is a good candidate for prevention and treatment of pigmentation disorders.

Keywords

MHY908 Skin Melanogenesis Tyrosinase inhibitor 

Notes

Acknowledgments

This research was supported by the 2014 Post-Doc. Development Program of Pusan National University. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2009-0083538) and the R&D program of MOTIE/KIAT (N0000697, Establishment of Infra Structure for Anti-aging Industry Support).

References

  1. Bilodeau, M.L., J.D. Greulich, R.L. Hullinger, C. Bertolotto, R. Ballotti, and O.M. Andrisani. 2001. BMP-2 stimulates tyrosinase gene expression and melanogenesis in differentiated melanocytes. Pigment Cell Research 14: 328–336.CrossRefPubMedGoogle Scholar
  2. Brenner, M., and V.J. Hearing. 2008. The protective role of melanin against UV damage in human skin. Photochemistry and Photobiology 84: 539–549.CrossRefPubMedCentralPubMedGoogle Scholar
  3. Karioti, A., A. Protopappa, N. Megoulas, and H. Skaltsa. 2007. Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. Bioorganic & Medicinal Chemistry 15: 2708–2714.CrossRefGoogle Scholar
  4. Khan, M.T. 2012. Novel tyrosinase inhibitors from natural resources—their computational studies. Current Medicinal Chemistry 19: 2262–2272.CrossRefPubMedGoogle Scholar
  5. Kim, Y.J., and H. Uyama. 2005. Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition mechanism and perspective for the future. Cellular and Molecular Life Sciences 62: 1707–1723.CrossRefPubMedGoogle Scholar
  6. Kim, S.S., C.G. Hyun, Y.H. Choi, and N.H. Lee. 2013. Tyrosinase inhibitory activities of the compounds isolated from Neolitsea aciculata (Blume) Koidz. Journal of Enzyme Inhibition and Medicinal Chemistry 28: 685–689.CrossRefPubMedGoogle Scholar
  7. Liang, C., J.H. Lim, S.H. Kim, and D.S. Kim. 2012. Dioscin: A synergistic tyrosinase inhibitor from the roots of Smilax china. Food Chemistry 134: 1146–1148.CrossRefPubMedGoogle Scholar
  8. Lourdes, M., M. Blanca, A. Ricard, R. Julia, and M. Lorenzo. 2013. Boerhaavia diffusa: PPAR γ activation to lighten skin spots. Cosmetic Technologies 16: 17–23.Google Scholar
  9. Morris, G.M., R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, and A.J. Olson. 2009. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry 30: 2785–2791.CrossRefPubMedCentralPubMedGoogle Scholar
  10. No, J.K., D.Y. Soung, Y.J. Kim, K.H. Shim, Y.S. Jun, S.H. Rhee, T. Yokozawa, and H.Y. Chung. 1999. Inhibition of tyrosinase by green tea components. Life Sciences 65: PL241–PL246.CrossRefPubMedGoogle Scholar
  11. Park, M.H., J.Y. Park, H.J. Lee, D.H. Kim, D. Park, H.O. Jeong, C.H. Park, P. Chun, H.R. Moon, and H.Y. Chung. 2013. Potent anti-diabetic effects of MHY908, a newly synthesized PPAR alpha/gamma dual agonist in db/db mice. PLoS ONE 8: e78815.CrossRefPubMedCentralPubMedGoogle Scholar
  12. Parvez, S., M. Kang, H.S. Chung, and H. Bae. 2007. Naturally occurring tyrosinase inhibitors: mechanism and applications in skin health, cosmetics and agriculture industries. Phytotherapy Research 21: 805–816.CrossRefPubMedGoogle Scholar
  13. Satooka, H., and I. Kubo. 2012. Resveratrol as a kcat type inhibitor for tyrosinase: Potentiated melanogenesis inhibitor. Bioorganic & Medicinal Chemistry 20: 1090–1099.CrossRefGoogle Scholar
  14. Tocco, G., A. Fais, G. Meli, M. Begala, G. Podda, M.B. Fadda, M. Corda, O.A. Attanasi, P. Filippone, and S. Berretta. 2009. PEG-immobilization of cardol and soluble polymer-supported synthesis of some cardol-coumarin derivatives: Preliminary evaluation of their inhibitory activity on mushroom tyrosinase. Bioorganic & Medicinal Chemistry Letters 19: 36–39.CrossRefGoogle Scholar
  15. Wolber, G., and T. Langer. 2005. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. Journal of Chemical Information and Modeling 45: 160–169.CrossRefPubMedGoogle Scholar
  16. Yoon, W.J., M.J. Kim, J.Y. Moon, H.J. Kang, G.O. Kim, N.H. Lee, and C.G. Hyun. 2010. Effect of palmitoleic acid on melanogenic protein expression in murine b16 melanoma. Journal of Oleo Science 59: 315–319.CrossRefPubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2014

Authors and Affiliations

  • Min Hi Park
    • 1
    • 2
  • Seong Jin Kim
    • 1
    • 2
  • Hyoung Oh Jeong
    • 1
    • 2
  • Kyoung Mi Moon
    • 1
    • 2
  • Sujin Son
    • 1
    • 2
  • Dae Hyun Kim
    • 1
    • 2
  • Hye Rim Kim
    • 1
    • 2
  • Min Jo Kim
    • 1
    • 2
  • Hwi Young Yun
    • 1
    • 2
  • Pusoon Chun
    • 4
  • Nam Kyung Je
    • 2
  • Takako Yokozawa
    • 4
  • Hyung Ryong Moon
    • 1
    • 3
  • Hae Young Chung
    • 1
    • 2
    Email author
  1. 1.Molecular Inflammation Research Center for Aging Intervention (MRCA), College of PharmacyPusan National UniversityBusanRepublic of Korea
  2. 2.College of PharmacyPusan National UniversityBusanRepublic of Korea
  3. 3.College of PharmacyInje UniversityGimhaeRepublic of Korea
  4. 4.Graduate School of Science and Engineering for ResearchUniversity of ToyamaToyamaJapan

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