Effect of p-aminophenols on tyrosinase activity

Yu Komori; Masahiko Imai; Takayasu Yamauchi; Kimio Higashiyama; Noriko Takahashi

doi:10.1016/j.bmc.2014.05.073

Effect of p-aminophenols on tyrosinase activity

Bioorg Med Chem. 2014 Aug 1;22(15):3994-4000. doi: 10.1016/j.bmc.2014.05.073. Epub 2014 Jun 11.

Authors

Yu Komori¹, Masahiko Imai¹, Takayasu Yamauchi², Kimio Higashiyama², Noriko Takahashi³

Affiliations

¹ Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
² Synthetic Organic Chemistry Research Laboratory, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
³ Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. Electronic address: t-noriko@hoshi.ac.jp.

PMID: 24972725
DOI: 10.1016/j.bmc.2014.05.073

Abstract

Tyrosinase is involved in the synthesis of melanin in the skin and hair as well as neuromelanin in the brain. This rate limiting enzyme catalyzes two critical steps (reactions) in melanogenesis; the hydroxylation of tyrosine to form DOPA and the subsequent oxidation of DOPA into dopaquinone. Several new aminophenol derivatives have been synthesized based on structure-activity relationship studies of N-(4-hydroxyphenyl)retinamide (1), a derivative of retinoic acid. In order to find new tyrosinase inhibitors, we investigated the effects of these p-aminophenols, including p-decylaminophenol (3), on the activity of mushroom tyrosinase. Compound 3 was the most potent agent, showing significant inhibition as compared with control. The inhibitory effects of 3 on tyrosinase activities were greater than seen with kojic acid, a well-known potent inhibitor of tyrosinase activity, which also causes adverse effects, including rash and dermatitis. A Lineweaver-Burk kinetic analysis of inhibition showed that 3 suppresses tyrosinase activity in a non-competitive fashion for both substrates, tyrosine and DOPA. These results suggest that 3 might be a useful alternative to kojic acid as a tyrosinase inhibitor.

Keywords: Kojic acid; Melanin; Tyrosinase activity; p-Aminophenol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agaricales / enzymology
Aminophenols / chemical synthesis
Aminophenols / chemistry*
Aminophenols / metabolism
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / metabolism
Kinetics
Monophenol Monooxygenase / antagonists & inhibitors*
Monophenol Monooxygenase / metabolism
Protein Binding
Pyrones / chemistry
Pyrones / metabolism
Structure-Activity Relationship
Tretinoin / analogs & derivatives
Tretinoin / chemistry

Substances

Aminophenols
Enzyme Inhibitors
Pyrones
Tretinoin
kojic acid
retinamide
Monophenol Monooxygenase
4-aminophenol