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

June Whan Park, Young Mi Ha, Kyung Mi Moon, So Ra Kim, Hyoung Oh Jeong, Yun Jung Park, Hye Jin Lee, Ji Young Park, Yu Min Song, Pusoon Chun, Youngjoo Byun, Hyung Ryong Moon, Hae Young Chung

Research output: Contribution to journalArticlepeer-review

Abstract

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 0.50 μM which was significantly lower than that of kojic acid (IC50 = 53.95 μM), 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.

Original languageEnglish (US)
Pages (from-to)4172-4176
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number14
DOIs
StatePublished - Jul 15 2013
Externally publishedYes

Keywords

  • Kojic acid
  • Melanogenesis
  • Skin-whitening product
  • Tyrosinase inhibitor 4-(6,7-Dihydro-5H-indeno[5,6-d]thiazol-2-yl)benzene-1,3-diol

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Fingerprint Dive into the research topics of 'De novo tyrosinase inhibitor: 4-(6,7-Dihydro-5H-indeno[5,6-d]thiazol-2-yl) benzene-1,3-diol (MHY1556)'. Together they form a unique fingerprint.

Cite this