Syntheses of hydroxy substituted 2-phenyl-naphthalenes as inhibitors of tyrosinase

• Published in: Bioorganic & medicinal chemistry letters 2007-01, Vol.17 (2), p.461-464
• Main Authors: Song, Suhee, Lee, Hyojin, Jin, Youngeup, Ha, Young Mi, Bae, Sungjin, Chung, Hae Young, Suh, Hongsuk
• Format: Article
• Language: English
• Subjects: Agaricales - enzymology; Biological and medical sciences; Crystallography, X-Ray; Dealkylation; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Hydroquinones - antagonists & inhibitors; Indicators and Reagents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Miscellaneous; Models, Molecular; Monophenol Monooxygenase - antagonists & inhibitors; Morus - chemistry; Naphthalenes - chemical synthesis; Naphthalenes - pharmacology; Oxyresveratrol; Pharmacology. Drug treatments; Pyrones - antagonists & inhibitors; Resveratrol; Stilbenes - antagonists & inhibitors; Stilbenes - chemistry; Tyrosinase; X-ray structure
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.10.025

Isosteres of oxyresveratrol and resveratrol and their derivatives with 2-phenyl-naphthalene template were synthesized and evaluated as tyrosinase inhibitors. Oxyresveratrol and resveratrol, with hydroxy substituted trans-stilbene structure, exert potent inhibitory effects on cyclooxygenase, rat liver mitochondrial ATPase activity, and tyrosinase. As the isosteres of oxyresveratrol, a new family of hydroxyl substituted phenyl-naphthalenes were synthesized to show excellent inhibition of mushroom tyrosinase. Compound 10, which is isostere of resveratrol, showed IC 50 value of 16.52 μM in mushroom tyrosinase activity. As compared to this, the reference compound, resveratrol, showed IC 50 value of 55.61 μM. Compound 4, which is isostere of oxyresveratrol, showed IC 50 value of 0.49 μM. Among the other three derivatives, compound 13 showed IC 50 value of 0.034 μM.