4-(6-Hydroxy-2-naphthyl)-1,3-bezendiol: A potent, new tyrosinase inhibitor

Abstract

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 (Ki 4.78 × 10-9 M at 0.125 μM and Ki 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. © 2007 Pharmaceutical Society of Japan.