De novo tyrosinase inhibitor: 4-(6,7-Dihydro-5H-indeno[5,6-d]thiazol-2-yl)benzene-1,3-diol (MHY1556)

In this study, we have synthesized and studied de novo tyrosinase inhibitor, MHY1556, which showed significantly better efficacy than other pre-existing tyrosinase inhibitors in vitro experiments. The IC50 value of MHY1556 was 0.50μM which was significantly lower than that of kojic acid (IC50=53.95μ...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-07, Vol.23 (14), p.4172-4176
Main Authors: Park, June Whan, Ha, Young Mi, Moon, Kyung-mi, Kim, So-ra, Jeong, Hyoung Oh, Park, Yun Jung, Lee, Hye Jin, Park, Ji Young, Song, Yu Min, Chun, Pusoon, Byun, Youngjoo, Moon, Hyung Ryong, Chung, Hae Young
Format: Article
Language:English
Subjects:
4-(6,7-Dihydro-5H-indeno[5,6-d]thiazol-2-yl)benzene-1,3-diol
Agaricales - enzymology
Animals
Benzothiazoles - chemical synthesis
Benzothiazoles - metabolism
Benzothiazoles - toxicity
Binding Sites
Cell Line, Tumor
Cell Survival - drug effects
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - metabolism
Enzyme Inhibitors - toxicity
Kojic acid
Melanogenesis
Mice
Molecular Docking Simulation
Monophenol Monooxygenase - antagonists & inhibitors
Monophenol Monooxygenase - metabolism
Protein Binding
Protein Structure, Tertiary
Pyrones - chemistry
Pyrones - metabolism
Pyrones - toxicity
Resorcinols - chemical synthesis
Resorcinols - metabolism
Resorcinols - toxicity
Skin-whitening product
Tyrosinase inhibitor
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Summary:In this study, we have synthesized and studied de novo tyrosinase inhibitor, MHY1556, which showed significantly better efficacy than other pre-existing tyrosinase inhibitors in vitro experiments. The IC50 value of MHY1556 was 0.50μM which was significantly lower than that of kojic acid (IC50=53.95μM), which is a well-known tyrosinase inhibitor and was used as a positive control in this study. We predicted the tertiary structure of tyrosinase, simulated the docking with compound MHY1556 and confirmed that the compound strongly interacts with mushroom tyrosinase residues. Substitutions with a hydroxy group at both R1 and R3 of the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase, especially through the hydrogen bonding interaction of the hydroxyl group at R1 with GLY281. In addition, MHY1556 showed concentration-dependent inhibitory effects in melanin content assay where B16F10 melanoma cells were treated with α-melanocyte stimulating hormone (α-MSH), and also there is no significant cytotoxicity of this compound in cell viability assay conducted in B16F10 melanoma cells. The tyrosinase activity assay results with MHY1556 also support its potent inhibitory effects. Therefore, our data strongly suggest MHY1556 suppresses the melanogenesis via a tyrosinase inhibitory effect.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.05.029