title: Effect of p-aminophenols on tyrosinase activity.
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.
authors: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors: Yu
authors: Y
authors: Komori
authors: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors: Masahiko
authors: M
authors: Imai
authors: Synthetic Organic Chemistry Research Laboratory, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors: Takayasu
authors: T
authors: Yamauchi
authors: Synthetic Organic Chemistry Research Laboratory, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors: Kimio
authors: K
authors: Higashiyama
authors: 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.
authors: Noriko
authors: N
authors: Takahashi
mesh_terms: D000363:Agaricales / Q000201:enzymology; D000627:Aminophenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000627:Aminophenols; D004791:Enzyme Inhibitors; D011753:Pyrones; D014212:Tretinoin; C011890:kojic acid; C054441:retinamide; D014442:Monophenol Monooxygenase; C026729:4-aminophenol
keywords: Kojic acid; Melanin; Tyrosinase activity; p-Aminophenol