IDENTIFICATION OF QUINOLINES THAT INHIBIT MELANOGENESIS BY ALTERING TYROSINASE FAMILY TRAFFICKING.

This study by scientists at the New York University School of Medicine and PTC Therapeutics demonstrated how MatTek’s MelanoDerm in vitro human skin tissue equivalent can be used to measure the depigmenting effects of human skin lightening agents. A series of quinolines, including chloroquine and quinine, were identified as potent pigmentation inhibitors through screening a compound library in murine melanocytes. Structure-activity relationship analysis indicated that 4-substituted amino groups with a tertiary amine side chain, such as chloroquine, were associated with robust inhibitory activity. In contrast to many previously identified pigmentation inhibitors, these newly identified inhibitors had no effect on either the level or the enzymatic activity of tyrosinase, the rate-limiting enzyme in melanin production. Rather, these results showed that these quinolines inhibited melanogenesis by disrupting the intracellular trafficking of tyrosinase-related proteins and lysosome-associated membrane protein 1 (Lamp-1). In treated melanocytes, tyrosinase and tyrosinase-related protein 1 accumulated in Lamp-1- positive perinuclear organelles instead of melanosomes, thus preventing melanogenesis. The depigmenting abilities of chloroquine and quinine salicylate were assessed in a human skin equivalent model (MelanoDerm). Both compounds were considerably more effective than arbutin, a widely used lightening agent. These results indicate that quinolines may be useful agents for “cosmeceutical” skin lightening and treatment of hyperpigmentation disorders.

Cosmeceuticals, EPI-100-NMM-113, Fontana-Masson silver stain, Intracellular trafficking, Lysome-associated membrane protein 1, MEL-300-A, MEL-300-B, MTT, MTT assay, Melanin content, MelanoDerm, Spectrum collection, Top view microscopy, Tyrosinase-related proteins

Arbutin, Chloroquine, Quinine salicylate, Water/PEG (30:70)