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Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated
as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06muM), 11 (IC(50)=2.09muM),
15 (IC(50)=2.61muM), and 27 (IC(50)=3.19muM) were found to be the most active compounds of
the series, even better than both standards kojic acid (IC(50)=16.67muM) and l-mimosine
(IC(50)=3.68muM). This study may lead to the discovery of therapeutically potent agents against
clinically very important dermatological disorders including hyperpigmentation as well as skin
melanoma.
- Kim DS, Park SH, Kwon SB, Youn SW, Park ES, Park KC.
Heat treatment decreases melanin synthesis via protein phosphatase 2 inactivation. Cell
Signal. 17(8):1023-31, 2005. Epub 2004 Dec 23.
In the present study, we investigated the effects of heat treatment on melanogenesis in a mouse
melanocyte cell line (Mel-Ab). It has been reported that activated extracellular signal-regulated
kinase (ERK) is responsible for microphthalmia-associated transcription factor (MITF)
degradation, which leads to a reduction in tyrosinase protein production and melanin synthesis.
Here we demonstrate that heat treatment induces sustained ERK activation, which may inhibit
melanogenesis. However, the specific ERK pathway inhibitors, PD98059 or U0126 did not restore
heat-induced hypopigmentation. Furthermore, PD98059 or U0126 hardly blocked the heat-induced
activation of ERK. These results suggest that heat treatment may inactivate protein phosphatase,
and thus ERK activation is maintained. To support this hypothesis, we examined the effects of heat
treatment on protein phosphatase 2A (PP2A) activity. The results obtained show that heat
treatment inactivates PP2A, which may subsequently cause ERK activation and that heat treatment
inhibits MITF promoter activity. Overall, our results demonstrate that heat treatment reduces
melanin production in a temperature-dependent manner.
- Kim HJ, Seo SH, Lee BG, Lee YS.
Identification of tyrosinase inhibitors from Glycyrrhiza uralensis. Planta Med. 71(8):785-7,
2005.
Tyrosinase is a key enzyme in the production of melanins. Phytochemical studies of a Glycyrrhiza
uralensis extract were performed by measuring the tyrosinase and melanin synthesis inhibitory
activity. Glycyrrhisoflavone and glyasperin C were identified as tyrosinase inhibitors for the first
time. Glyasperin C showed a stronger tyrosinase inhibitory activity (IC (50) = 0.13 +/- 0.01
microg/mL) than glabridin (IC (50) = 0.25 +/- 0.01 microg/mL) and a moderate inhibition of
melanin production (17.65 +/- 8.8 % at 5 microg/mL). Glycyrrhisoflavone showed a strong
melanin synthesis inhibitory activity (63.73 +/- 6.8 % inhibition at 5 microg/mL). These results
suggest that glyasperin C and glycyrrhisoflavone could be promising candidates in the design of
skin-whitening agents.
- Kim YJ, Uyama H.
Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism
and perspective for the future. Cell Mol Life Sci. 62(15):1707-23, 2005.
Tyrosinase is known to be a key enzyme in melanin biosynthesis, involved in determining the color
of mammalian skin and hair. Various dermatological disorders, such as melasma, age spots and
sites of actinic damage, arise from the accumulation of an excessive level of epidermal
pigmentation. In addition, unfavorable enzymatic browning of plant-derived foods by tyrosinase
causes a decrease in nutritional quality and economic loss of food products. The inadequacy of
current conventional techniques to prevent tyrosinase action encourages us to seek new potent
tyrosinase inhibitors. This article overviews the various inhibitors obtained from natural and
synthetic sources with their industrial importance.
- Komarov DA, Slepneva IA, Glupov VV, Khramtsov VV.
Superoxide and hydrogen peroxide formation during enzymatic oxidation of DOPA by
phenoloxidase. Free Radic Res. 39(8):853-8, 2005.
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