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Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents

Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase...

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Autores principales: Lee, Ji Young, Lee, Jooyun, Min, Daejin, Kim, Juewon, Kim, Hyoung-June, No, Kyoung Tai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246559/
https://www.ncbi.nlm.nih.gov/pubmed/32365630
http://dx.doi.org/10.3390/ijms21093144
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author Lee, Ji Young
Lee, Jooyun
Min, Daejin
Kim, Juewon
Kim, Hyoung-June
No, Kyoung Tai
author_facet Lee, Ji Young
Lee, Jooyun
Min, Daejin
Kim, Juewon
Kim, Hyoung-June
No, Kyoung Tai
author_sort Lee, Ji Young
collection PubMed
description Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key enzyme in melanogenesis, identified using docking-based high throughput virtual screening of an in-house natural compound library followed by mushroom tyrosinase inhibition assay. Of the three compounds, gallacetophenone showed high anti-melanogenic effect in both human epidermal melanocytes and a 3D human skin model, MelanoDerm. The inhibitory effect of gallacetophenone on tyrosinase was elucidated by computational molecular modeling at the atomic level. Binding of gallacetophenone to the active site of tyrosinase was found to be stabilized by hydrophobic interactions with His367, Ile368, and Val377; hydrogen bonding with Ser380 and a water molecule bridging the copper ions. Thus, our results strongly suggested gallacetophenone as an anti-melanogenic ingredient that inhibits tyrosinase.
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spelling pubmed-72465592020-06-10 Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents Lee, Ji Young Lee, Jooyun Min, Daejin Kim, Juewon Kim, Hyoung-June No, Kyoung Tai Int J Mol Sci Article Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key enzyme in melanogenesis, identified using docking-based high throughput virtual screening of an in-house natural compound library followed by mushroom tyrosinase inhibition assay. Of the three compounds, gallacetophenone showed high anti-melanogenic effect in both human epidermal melanocytes and a 3D human skin model, MelanoDerm. The inhibitory effect of gallacetophenone on tyrosinase was elucidated by computational molecular modeling at the atomic level. Binding of gallacetophenone to the active site of tyrosinase was found to be stabilized by hydrophobic interactions with His367, Ile368, and Val377; hydrogen bonding with Ser380 and a water molecule bridging the copper ions. Thus, our results strongly suggested gallacetophenone as an anti-melanogenic ingredient that inhibits tyrosinase. MDPI 2020-04-29 /pmc/articles/PMC7246559/ /pubmed/32365630 http://dx.doi.org/10.3390/ijms21093144 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Ji Young
Lee, Jooyun
Min, Daejin
Kim, Juewon
Kim, Hyoung-June
No, Kyoung Tai
Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
title Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
title_full Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
title_fullStr Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
title_full_unstemmed Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
title_short Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
title_sort tyrosinase-targeting gallacetophenone inhibits melanogenesis in melanocytes and human skin- equivalents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246559/
https://www.ncbi.nlm.nih.gov/pubmed/32365630
http://dx.doi.org/10.3390/ijms21093144
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