Biol. Pharm. Bull., 30(9),1711-1715, September 2007

Regular Articles

4-(6-Hydroxy-2-naphthyl)-1,3-bezendiol: A Potent, New Tyrosinase Inhibitor

Young Mi HA,^a Sang Woon CHUNG,^a Suhee SONG,^b Hyojin LEE,^b Hongsuk SUH,^b and Hae Young CHUNG^*,a

^a Department of Pharmacy, Pusan National University; Kumjeong-Gu, Busan 609-735, Korea: and ^b Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University; Busan 609-735, Korea. * To whom correspondence should be addressed. e-mail: hyjung@pusan.ac.kr

Tyrosinase is a key enzyme for melanin biosynthesis and known to be sensitive to ultraviolet light in the presence of oxygen. Therefore, finding effective tyrosinase inhibitors, either from synthetic or natural sources, can be beneficial in the treatment of melanin-related disorders. We synthesized 4-(6-hydroxy-2-naphthyl)-1,3-bezendiol (HNB), a new family of hydroxyl substituted phenyl naphthalenes, as the isosteres of oxyresveratrol. This study investigated inhibitory effects of HNB on tyrosinase activity. HNB inhibited mushroom tyrosinase with an IC₅₀ value of 0.07 μM, which is more potent than the anti-tyrosinase activity of kojic acid (IC₅₀=38.24), a well-known tyrosinase inhibitor. The kinetic analysis of tyrosinase inhibition revealed that HNB is a competitive inhibitor (K_i 4.78×10⁻⁹ M at 0.125 μM and K_i 6.21×10⁻⁹ M at 0.25 μM). We further found that HNB also inhibited melanin production in B16F10 melanoma cells (B16 cells). In addition to tyrosinase inhibiting activity, melanin biosynthesis was inhibited by HNB in the B16F10 cells. These data strongly suggest that HNB can suppress the production of melanin via the modulation of tyrosinase activity.

Key words 4-(6-hydroxy-2-naphthyl)-1,3-bezendiol (HNB); tyrosinase inhibitor; melanin biosynthesis