A Potent Tyrosinase Inhibitor, (E)-3-(2,4-Dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one, with Anti-Melanogenesis Properties in α-MSH and IBMX-Induced B16F10 Melanoma Cells

In this study, we designed and synthesized eight thiophene chalcone derivatives (1a–h) as tyrosinase inhibitors and evaluated their mushroom tyrosinase inhibitory activities. Of these eight compounds, (E)-3-(2,4-dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one (1c) showed strong competitive inhibition activity against mushroom tyrosinase with IC50 values of 0.013 μM for tyrosine hydroxylase and 0.93 μM for dopa oxidase. In addition, we used enzyme kinetics study and docking program to further evaluate the inhibitory mechanism of 1c toward tyrosinase. As an underlying mechanism of 1c mediated anti-melanogenic effect, we investigated the inhibitory activity against melanin contents and cellular tyrosinase in B16F10 melanoma cells. As the results, the enzyme kinetics and docking results supports that 1c highly interacts with tyrosinase residues in the tyrosinase active site and it can directly inhibit tyrosinase as competitive inhibitor. In addition, 1c exhibited dose-dependent inhibitory effects in melanin contents and intracellular tyrosinase on α-MSH and IBMX-induced B16F10 cells. Overall, our results suggested that 1c might be considered potent tyrosinase inhibitor for use in the development of therapeutic agents for diseases associated with hyperpigment disorders.

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Mushroom Tyrosinase Inhibition and Antimelanogenesis Activities of <i>Bacopa monnieri</i> (L.) Methanol Extract in B16F10 Melanoma Cells

Journal of Biosciences and Medicines ◽

10.4236/jbm.2020.85018 ◽

2020 ◽

Vol 08 (05) ◽

pp. 189-202

Author(s):

T. N. Shamu ◽

Junna Lalitha ◽

Manohar Shinde

Keyword(s):

Methanol Extract ◽

Melanoma Cells ◽

Bacopa Monnieri ◽

Mushroom Tyrosinase ◽

B16f10 Melanoma ◽

Tyrosinase Inhibition ◽

B16f10 Melanoma Cells

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Kinetics of Mushroom Tyrosinase and Melanogenesis Inhibition byN-Acetyl-pentapeptides

The Scientific World JOURNAL ◽

10.1155/2014/409783 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Ching-Yi Lien ◽

Ching-Yu Chen ◽

Shih-Ting Lai ◽

Chin-Feng Chan

Keyword(s):

Kojic Acid ◽

Lag Time ◽

Melanoma Cells ◽

Dependent Manner ◽

Mushroom Tyrosinase ◽

Inhibitory Effects ◽

B16f10 Melanoma ◽

B16f10 Melanoma Cells ◽

Kinetics Of ◽

Dose Dependent

We investigated the kinetics of 4N-acetyl-pentapeptides, Ac-P1, Ac-P2, Ac-P3, and Ac-P4, regarding inhibition of mushroom tyrosinase activity. The peptides sequences of Ac-P1, Ac-P2, Ac-P3, and Ac-P4 were Ac-RSRFK, Ac-KSRFR, Ac-KSSFR, and Ac-RSRFS, respectively. The 4N-acetyl-pentapeptides were able to reduce the oxidation ofL-DOPA by tyrosinase in a dose-dependent manner. Of the 4N-acetyl-pentapeptides, only Ac-P4 exhibited lag time (80 s) at a concentration of 0.5 mg/mL. The tyrosinase inhibitory effects of Ac-P4 (IC500.29 mg/mL) were more effective than those of Ac-P1, Ac-P2, and Ac-P3, in which IC50s were 0.75 mg/mL, 0.78 mg/mL, and 0.81 mg/mL, respectively. Kinetic analysis demonstrated that all 4N-acetyl-pentapeptides were mixed-type tyrosinase inhibitors. Furthermore, 0.1 mg/mL of Ac-P4 exhibited significant melanogenesis inhibition on B16F10 melanoma cells and was more effective than kojic acid. The melanogenesis inhibition of Ac-P4 was dose-dependent and did not induce any cytotoxicity on B16F10 melanoma cells.

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Inhibitory Effect of Phlorotannins Isolated from Ecklonia cava on Mushroom Tyrosinase Activity and Melanin Formation in Mouse B16F10 Melanoma Cells

Journal of Agricultural and Food Chemistry ◽

10.1021/jf900006f ◽

2009 ◽

Vol 57 (10) ◽

pp. 4124-4129 ◽

Cited By ~ 108

Author(s):

Na Young Yoon ◽

Tae-Kil Eom ◽

Moon-Moo Kim ◽

Se-Kwon Kim

Keyword(s):

Inhibitory Effect ◽

Melanoma Cells ◽

Tyrosinase Activity ◽

Ecklonia Cava ◽

Mushroom Tyrosinase ◽

B16f10 Melanoma ◽

Melanin Formation ◽

B16f10 Melanoma Cells

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GSK-3β-Targeting Fisetin Promotes Melanogenesis in B16F10 Melanoma Cells and Zebrafish Larvae through β-Catenin Activation

International Journal of Molecular Sciences ◽

10.3390/ijms21010312 ◽

2020 ◽

Vol 21 (1) ◽

pp. 312 ◽

Cited By ~ 2

Author(s):

Ilandarage Menu Neelaka Molagoda ◽

Wisurumuni Arachchilage Hasitha Maduranga Karunarathne ◽

Sang Rul Park ◽

Yung Hyun Choi ◽

Eui Kyun Park ◽

...

Keyword(s):

Molecular Docking ◽

Glycogen Synthase ◽

Melanoma Cells ◽

Functional Assay ◽

Mushroom Tyrosinase ◽

B16f10 Melanoma ◽

Zebrafish Larvae ◽

B16f10 Melanoma Cells ◽

Gsk 3Β

Fisetin is found in many fruits and plants such as grapes and onions, and exerts anti-inflammatory, anti-proliferative, and anticancer activity. However, whether fisetin regulates melanogenesis has been rarely studied. Therefore, we evaluated the effects of fisetin on melanogenesis in B16F10 melanoma cell and zebrafish larvae. The current study revealed that fisetin slightly suppressed in vitro mushroom tyrosinase activity; however, molecular docking data showed that fisetin did not directly bind to mushroom tyrosinase. Unexpectedly, fisetin significantly increased intracellular and extracellular melanin production in B16F10 melanoma cells regardless of the presence or absence of α-melanocyte stimulating hormone (α-MSH). We also found that the expression of melanogenesis-related genes such as tyrosinase and microphthalmia-associated transcription factor (MITF), were highly increased 48 h after fisetin treatment. Pigmentation of zebrafish larvae by fisetin treatment also increased at the concentrations up to 200 µM and then slightly decreased at 400 µM, with no alteration in the heart rates. Molecular docking data also revealed that fisetin binds to glycogen synthase kinase-3β (GSK-3β). Therefore, we evaluated whether fisetin negatively regulated GSK-3β, which subsequently activates β-catenin, resulting in melanogenesis. As expected, fisetin increased the expression of β-catenin, which was subsequently translocated into the nucleus. In the functional assay, FH535, a Wnt/β-catenin inhibitor, significantly inhibited fisetin-mediated melanogenesis in zebrafish larvae. Our data suggested that fisetin inhibits GSK-3β, which activates β-catenin, resulting in melanogenesis through the revitalization of MITF and tyrosinase.

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Kinetic Aspects of the Interaction of Blood Clotting Enzymes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651214 ◽

1968 ◽

Vol 19 (03/04) ◽

pp. 364-367 ◽

Cited By ~ 4

Author(s):

H. C Hemker ◽

P. W Hemker

Keyword(s):

Enzyme Kinetics ◽

Blood Clotting ◽

Competitive Inhibition ◽

Competitive Inhibitor ◽

Kinetics Of

SummaryThe enzyme kinetics of competitive inhibition under conditions prevailing in clotting tests are developed and a method is given to measure relative amounts of a competitive inhibitor by means of the t — D plot.

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