Novel tyrosinase inhibitors from liquid culture of Neolentinus lepideus.

Abstract

Tyrosinase is the key enzyme that controls melanin formation in the human skin. We performed a screening of 96 extracts of mushroom cultures and fruiting bodies for examining their inhibitory activity against mushroom tyrosinase. The ethyl acetate extracts of culture filtrate of Neolentinus lepideus exhibited the strongest inhibitory activity. The active compounds 1 and 2 were purified by repeated chromatographic separations from the extract. On the basis of spectroscopic analyses, 1 and 2 were identified to be 1,3-dihydroisobenzofuran-4,5,7-triol and 5-methoxy-1,3-dihydroisobenzofuran-4,7-diol, respectively. Lineweaver-Burk plot of the enzyme reaction in the presence of 1 indicated that 1 was a potent competitive inhibitor. The respective IC50 values of 1 and 2 were 173 and 263 μg/mL. Compound 1 at 15 μg/mL suppressed melanin accumulation stimulated by α-MSH in the murine melanoma B16 cells, as well as the induced accumulation of both tyrosinase transcript and protein without inhibiting cell proliferation.

• Authors: Atsushi Ishihara, Yuri Ide, Tomohiro Bito, Naoki Ube, Naoki Endo, Kozue Sotome, Nitaro Maekawa, Kotomi Ueno, Akira Nakagiri
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 82 Issue 1 Pg. 22-30 (Jan 2018) ISSN: 1347-6947 [Electronic] England
• PMID: 29297258 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Melanins
• Plant Extracts
• Monophenol Monooxygenase

Topics

• Agaricales (chemistry)
• Animals
• Cell Line, Tumor
• Enzyme Inhibitors (chemistry, pharmacology)
• Inhibitory Concentration 50
• Melanins (antagonists & inhibitors)
• Melanoma, Experimental
• Monophenol Monooxygenase (antagonists & inhibitors)
• Plant Extracts (chemistry, pharmacology)