Identification of L-Cysteinamide as a Potent Inhibitor of Tyrosinase-Mediated Dopachrome Formation and Eumelanin Synthesis.

Hyun Kyung Lee,Yong Chool Boo,Jae Won Ha,Yun Jeong Hwang

doi:10.3390/antiox10081202

Abstract

The purpose of this study is to identify amino acid derivatives with potent anti-eumelanogenic activity. First, we compared the effects of twenty different amidated amino acids on tyrosinase (TYR)-mediated dopachrome formation in vitro and melanin content in dark-pigmented human melanoma MNT-1 cells. The results showed that only L-cysteinamide inhibited TYR-mediated dopachrome formation in vitro and reduced the melanin content of cells. Next, the antimelanogenic effect of L-cysteinamide was compared to those of other thiol compounds (L-cysteine, N-acetyl L-cysteine, glutathione, L-cysteine ethyl ester, N-acetyl L-cysteinamide, and cysteamine) and positive controls with known antimelanogenic effects (kojic acid and β-arbutin). The results showed the unique properties of L-cysteinamide, which effectively reduces melanin content without causing cytotoxicity. L-Cysteinamide did not affect the mRNA and protein levels of TYR, tyrosinase-related protein 1, and dopachrome tautomerase in MNT-1 cells. L-Cysteinamide exhibited similar properties in normal human epidermal melanocytes (HEMs). Experiments using mushroom TYR suggest that L-cysteinamide at certain concentrations can inhibit eumelanin synthesis through a dual mechanism by inhibiting TYR-catalyzed dopaquinone synthesis and by diverting the synthesized dopaquinone to the formation of DOPA-cysteinamide conjugates rather than dopachrome. Finally, L-cysteinamide was shown to increase pheomelanin content while decreasing eumelanin and total melanin contents in MNT-1 cells. This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and HEMs, and will be useful in controlling skin hyperpigmentation.

Highlights

Melanin pigment is important for skin color development and for maintaining homeostasis in various organs including the skin [1,2]
This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and human epidermal melanocytes (HEMs), and will be useful in controlling skin hyperpigmentation
Does L-cysteinamide have any advantageous properties in terms of activity or safety compared to other antimelanogenic compounds? We addressed this question by comparing the activities of L-cysteinamide with those of other thiol compounds, such as L-cysteine, N-acetyl L-cysteine, and glutathione, as well as positive controls

Summary

Introduction

Melanin pigment is important for skin color development and for maintaining homeostasis in various organs including the skin [1,2]. Disrupted melanin metabolism results in hypopigmentation and hyperpigmentation [3,4]. Hypopigmentation can occur when melanin synthesis is genetically or epigenetically impaired [5,6]. Hypopigmentation is caused by mutations in various genes that regulate melanocytic development (piebaldism, Waardenburg syndrome, and Tietz syndrome), melanin synthesis (oculocutaneous albinism), and melanosome transfer to keratinocytes (Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome) [7]. Hyperpigmentation can occur as a result of inflammatory reactions or aging of the skin [8,9]. Skin pigmentary disorders are important from dermatological and aesthetic points of view, and more effective and safe treatment is needed [10,11,12,13]

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