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4-(Phenylsulfanyl)butan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo

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ABSTRACT

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.

No MeSH data available.


The inhibitory mechanism of 4-(phenylsulfanyl)butan-2-one on mushroom tyrosinase. The data for Lineweaver-Burk plots were obtained as mean values of three independent assays with various concentrations of l-tyrosine as the substrate. The reactions were performed in the presence of 4-(phenylsulfanyl)butan-2-one at 50 µM.
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ijms-16-20240-f001: The inhibitory mechanism of 4-(phenylsulfanyl)butan-2-one on mushroom tyrosinase. The data for Lineweaver-Burk plots were obtained as mean values of three independent assays with various concentrations of l-tyrosine as the substrate. The reactions were performed in the presence of 4-(phenylsulfanyl)butan-2-one at 50 µM.

Mentions: We calculated the mushroom tyrosinase inhibition activity of dozens of pure compounds from marine creatures in vitro. We searched for a new and efficient substance for hyper-pigmentation prevention and skin whitening and discovered that one compound, 4-(phenylsulfanyl)butan-2-one, significantly diminished mushroom tyrosinase activity (Table 1), thus, we then synthesized it. It exhibited strong dose-dependent inhibitions of mushroom tyrosinase activities. Additionally, we verified the tyrosinase enzyme kinetics with 4-(phenylsulfanyl)butan-2-one at various concentrations of the l-tyrosine substrate (0.1, 0.2, 0.3, and 0.4 mM). The Lineweaver–Burk equation plot (Figure 1) confirmed that it acts as a noncompetitive inhibitor. The Km value was 1.11 × 10−4 M, and the Vmax value of mushroom tyrosinase activity was 1.05 × 10−1 mM/min, respectively, with no inhibitor. The kinetic analysis in the presence of 50 µM testing compound revealed a Km value of 1.23 × 10−4 M, Vmax value of 7.22 × 10−2 mM/min, and Ki value of 3.45 × 10−5 M.


4-(Phenylsulfanyl)butan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo
The inhibitory mechanism of 4-(phenylsulfanyl)butan-2-one on mushroom tyrosinase. The data for Lineweaver-Burk plots were obtained as mean values of three independent assays with various concentrations of l-tyrosine as the substrate. The reactions were performed in the presence of 4-(phenylsulfanyl)butan-2-one at 50 µM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4613201&req=5

ijms-16-20240-f001: The inhibitory mechanism of 4-(phenylsulfanyl)butan-2-one on mushroom tyrosinase. The data for Lineweaver-Burk plots were obtained as mean values of three independent assays with various concentrations of l-tyrosine as the substrate. The reactions were performed in the presence of 4-(phenylsulfanyl)butan-2-one at 50 µM.
Mentions: We calculated the mushroom tyrosinase inhibition activity of dozens of pure compounds from marine creatures in vitro. We searched for a new and efficient substance for hyper-pigmentation prevention and skin whitening and discovered that one compound, 4-(phenylsulfanyl)butan-2-one, significantly diminished mushroom tyrosinase activity (Table 1), thus, we then synthesized it. It exhibited strong dose-dependent inhibitions of mushroom tyrosinase activities. Additionally, we verified the tyrosinase enzyme kinetics with 4-(phenylsulfanyl)butan-2-one at various concentrations of the l-tyrosine substrate (0.1, 0.2, 0.3, and 0.4 mM). The Lineweaver–Burk equation plot (Figure 1) confirmed that it acts as a noncompetitive inhibitor. The Km value was 1.11 × 10−4 M, and the Vmax value of mushroom tyrosinase activity was 1.05 × 10−1 mM/min, respectively, with no inhibitor. The kinetic analysis in the presence of 50 µM testing compound revealed a Km value of 1.23 × 10−4 M, Vmax value of 7.22 × 10−2 mM/min, and Ki value of 3.45 × 10−5 M.

View Article: PubMed Central - PubMed

ABSTRACT

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.

No MeSH data available.