Synthesis and evaluation of bibenzyl glycosides as potent tyrosinase inhibitors

• Published in: European journal of medicinal chemistry 2011-04, Vol.46 (4), p.1374-1381
• Main Authors: Tajima, Reiko, Oozeki, Hiromi, Muraoka, Seiichi, Tanaka, Saori, Motegi, Yukari, Nihei, Hiroyuki, Yamada, Yoichi, Masuoka, Noriyoshi, Nihei, Ken-ichi
• Format: Article
• Language: English
• Subjects: Bibenzyl glycoside; Biological and medical sciences; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Glycosylation; Inhibitory Concentration 50; Medical sciences; Miscellaneous; Monophenol Monooxygenase - antagonists & inhibitors; Pharmacology. Drug treatments; Tyrosinase inhibitor; Wittig reaction
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.01.065

Bibenzyl glycosides 1– 6 were synthesized from 2,4-dihydoxybenzaldehyde and xylose, glucose, cellobiose or maltose. The key steps in the synthesis were the Wittig reaction and trichloroacetimidate glycosylation. Tests for tyrosinase inhibitory activity showed that all were significantly active, indicating that they are unique hydrophilic tyrosinase inhibitors. Bibenzyl xyloside 2 is a particularly potent inhibitor (IC 50 = 0.43 μM, 17 times higher than that of kojic acid). These results suggest that the hydrophilic cavity of tyrosinase might accommodate the bulky carbohydrate on the bibenzyl scaffold. Potent and hydrophilic tyrosinase inhibitors have been designed, on the basis of the bibenzyl glycoside scaffold. [Display omitted] ► Bibenzyl xyloside, glucoside, cellobioside and maltoside have been synthesized. ► The key steps were the Wittig reaction and trichloroacetimidate glycosylation. ► Tests for tyrosinase inhibitory activity showed that all were significantly active. ► Bibenzyl xyloside is a particularly potent inhibitor (IC 50 = 0.43 μM). ► The bibenzyl glycosides are unique hydrophilic tyrosinase inhibitors.