title: De novo tyrosinase inhibitor: 4-(6,7-dihydro-5H-indeno[5,6-d]thiazol-2-yl)benzene-1,3-diol (MHY1556).
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 0.50μM 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.
authors.affiliation: Molecular Inflammation Research Centre for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Kumjeong-Gu, Busan 609-735, Republic of Korea.
authors.forename: June Whan
authors.initials: JW
authors.lastname: Park
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Kyoung-mi
authors.initials: KM
authors.lastname: Moon
authors.forename: Kyung-mi
authors.initials: KM
authors.lastname: Moon
authors.forename: So-ra
authors.initials: SR
authors.lastname: Kim
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jeong
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Yu Min
authors.initials: YM
authors.lastname: Song
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000363:Agaricales / Q000201:enzymology; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D012118:Resorcinols / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity
chemical_list: C585742:4-(6,7-dihydro-5H-indeno(5,6-d)thiazol-2-yl)benzene-1,3-diol; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D011753:Pyrones; D012118:Resorcinols; C011890:kojic acid; D014442:Monophenol Monooxygenase