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KMID : 0613820170270020139
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Journal of Life Science
2017 Volume.27 No. 2 p.139 ~ p.148
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Tyrosinase Inhibitory Effect of (E)-2-(substituted benzylidene)-2,3-dihydro- 1H-cyclopenta[a]naphthalen-1-one Derivatives
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Lee Eun-Kyeong
Kim Ju-Hyun
Moon Kyoung-Mi
Ha Su-Gyeong
Noh Sang-Gyun
Kim Dae-Hyun
Lee Bong-Gi
Kim Do-Hyun
Kim Su-Jeong
Ullah Sultan
Moon Hyung-Ryong
Chung Hae-Young
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Abstract
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The inhibition of tyrosinase, a key enzyme in mammalian melanin synthesis, plays an important role in preventing skin pigmentation and melanoma. Therefore, tyrosinase inhibitors are very important in the fields of medicine and cosmetics. However, only a few tyrosinase inhibitors are currently available because of their toxic effects on skin or lack of selectivity and stability. Therefore, we synthesized a novel series of (E)-2-(substituted benzylidene)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one derivatives and evaluated their inhibitory effects on mushroom tyrosinase, with the aim of discovering a novel tyrosinase inhibitor. Among 19 derivatives, MHY3655 (IC50 = 0.1456 μM) showed the strongest inhibitory effect on tyrosinase activity compared to kojic acid (IC50 = 17.2 μM), a well-known tyrosinase inhibitor. In addition, MHY3655 showed competitive inhibition on Lineweaver-Burk plots. We confirmed that MHY3655 strongly interacts with mushroom tyrosinase residues through the docking simulation. Substitutions with a hydroxy group at both R2 and R4 in the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase. Further, MHY3655 did not show cytotoxicity at the concentrations tested in B16F10 melanoma cells. In conclusion, the novel compound MHY3655 potentially shows tyrosinase inhibitory activity, and it could be used as an ingredient in whitening cosmetics.
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KEYWORD
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Melanin, MHY3655, skin, (E)-2-(substituted benzylidene)-2,3-dihydro-1H-cyclopenta[a] naphthalen-1-one, tyrosinase inhibitor
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