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Top1. Introduction
Melanin is the principal dark surface pigments of uncertain structure that is widespread in nature and play a major role in protect the skin from ultraviolet (UV) damage by absorbing UV sunlight and removing reactive oxygen species (ROS) (Kim & Uyama, 2005; Prota, 1992). Melanin is found in bacteria, fungi, plants, animals and subserves a multitude of diverse functions with evolutionary significance(Prota, 1988). In humans (and in vertebrates in general), the biosynthesis of melanin involves a metabolic pathway beginning with the oxidation of tyrosine to an orthoquinone, dopaquinone, followed by a series of divergent steps that give rise to a predominantly indolic pigment (eumelanin) and a closely related pigment containing benzothiazine subunits (phaeomelanin) (Prota, 1992). Normal skin coloration is a result of both efficient melanization of the melanosome in the melanocyte and proper transfer to and receipt of the melanosome in the keratinocyte (Boissy, 2003; Seiberg, 2001). It is determined by a number of factors, the most important of which is the degree and distribution of melanin pigmentation (Spritz & Hearing, 1994). When a person is healthy, his or her skin will appear normal in color. In the case of illness or injury, the person’s skin might change color, becoming darker (hyperpigmentation), or lighter (hypopigmentation).
Hyperpigmentation such as melasma (also known as chloasma), freckles and moles is caused by an increase in melanin production and deposition. As a result of their prevalent localization in photoexposed areas, acquired hyperpigmentation have psychosocial and cosmetic relevance, and many efforts have been devoted to screening recognized and putative depigmenting agents (Briganti, Camera, & Picardo, 2003). Melanogenesis has been defined as the entire process leading to the formation melanin (Rescigno, Sollai,Pisu, Rinaldi, & Sanjust, 2002). In this process, tyrosinase (monophenol, polyphenol oxidase; EC 1.14.18.1) is the rate-limiting enzyme, catalyzing the first two initial steps of this pathway in the presence of molecular oxygen (Lerch, 1981; Robb, 1981; Solomon, Sundaram, & Machonkin, 1996). Therefore, tyrosinase inhibitors (TI) have attracted considerable interest in medicinal and cosmetic products, primarily in relation to the treatment of hyperpigmentation (Chen & Kubo, 2002). The most popular depigmenting agent is hydroquinone (dihydroxybenzene; HQ) as a TI introduced for clinical use since 1996. Several trials have demonstrated its therapeutic efficacy alone or in association with other compounds (Fisher, 1998; Guevara & Pandya, 2001; Kang, Chun, & Lee, 1998; Kauh & Zachian, 1999; Perez-Bernal, Munoz-Perez, & Camacho, 2000; Sanchez & Vazquez, 1982). Other whitening agents specifically acting on tyrosinase by different mechanisms have been also discovered. Moreover, all of them have presented problems related with the efficacy and safety that limit their uses in clinic. Wherefore, the discovery of new TI compounds needs special attention. But actually this type of study is mostly based in traditional method “trial and error” that implicates expensive and time consuming (Watson, 2003).