We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms.
- Authors
Song, Hyerim; Hwang, Yun Jeong; Ha, Jae Won; Boo, Yong Chool
- Abstract
The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1–1.5 µM) as compared to β-arbutin (IC50, 500–700 µM) or kojic acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders
- Subjects
MELANOGENESIS; HISTONE deacetylase; PHENOL oxidase; EPIGENETICS; MICROPHTHALMIA-associated transcription factor; DEACETYLASES; CATALYTIC activity
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 13, p4589
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21134589