Melanine biosynthesis

Melanin biosynthesis in animals is a complex process starting with the L-tyrosine amino acid. In the first step, L-tyrosine is converted first into DOPA and then into dopaquinone, a process catalyzed by tyrosinase. In the biosynthesis of eumelanins, dopaquinone undergoes a cyclization to form dopachrome and subsequently a tau-tomerization into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). DHICA is further oxidized to indole-5,6-quinone2-carboxylic acid, the precnrsor of DHICA eumelanins. Tyrosinase-related proteins TRP-2 and TRP-1, respectively, are responsible for the last two steps, and they are under the control of the tyrosinase promoter. 

Very recently, the method has been used for the synthesis of racemic linderol A [311], a natural product isolated from the fresh bark of Lindera umbellata. This compound is reported to exhibit potent inhibitory activity on the melanin biosynthesis of cultured B-16 melanoma cells in guinea pigs, without causing any cytotoxicity in the cultured cell or skin irritation [312]. 

Costa C, Bertazzo A, Allegri G, Toffano G, Curcuruto O, et al. 1992. Melanin biosynthesis from dopamine. II. A mass spectrometric and collisional spectroscopic investigation. Pigment Cell Res 5 122. 

CE133 Matsuda, H., S. Nakamura, and M. Kubo. Studies on cuticle drugs from natural sources. II. Inhibitory effect of Prunus plants on melanin biosynthesis. Biol Pharm Bull 1994 17(10) 1417-1420. 

Mimaki, Y. et ah, A novel hexahydrodibenzofuran derivative with potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells from Lindera umbellata bark, Chem. Pharm. Bull, 43, 893, 1995. 

Melanin is a collective term for brown or black pigments. They are condensates of phenolics and are widely distributed in nature, examples of this diverse chemistry being found in animals, plants and fungi. They perform various roles but in some fungi, notably Pyricularia oryzae and Colletotrichum spp., melanin biosynthesis is an essential feature in pathogenicity, the biosynthesis of melanin in appressorial walls being a requirement for the development of infection hyphae and subsequent penetration of the host epidermis. For example, melanin-deficient mutants of P. oryzae are not pathogenic. 

Three compounds have been developed that utilise the inhibition of melanin biosynthesis as the basis of disease control (Figure 4.18). The first and most valuable of these is tricyclazole. Tricyclazole is readily absorbed by the foliage and roots of rice plants and redistributed acropetally. On treated plants, conidial germination of P. oryzae and... 

Tricyclazole is reported to inhibit the melanin biosynthesis pathway between 1,3,8 trihydoxynaphthalene and vermelone whereas chromatographic analysis of P. oryzae culture media indicates that KTU 3616 treatment stimulates the accumulation of the intermediate, scytalone. 

Another group of fungicides interferes with cell wall formation. Two examples of this group include 1) the polyoxines, which prevent chitin formation by competitively inhibiting chitin-synthase, the final enzyme involved in chitin biosynthesis, and 2) melanine biosynthesis inhibitors, especially in Pyricularia oryzae. Examples of... 

Lee SH, Choi SY, Kim H et al. Mulberroside F isolated from the leaves of Moms alba inhibits melanin biosynthesis. Biol Pharm Bull 2002 25 1045-8. 

Pauciflorines A (268) and B (269) from Kopsia pauciflora are notable for being rare examples of plant-derived indole alkaloids which showed potent inhibitory activity (equivalent to that of the commercial compound, arbutin) towards melanin biosynthesis in cultured B16 melanoma cells at concentrations of 13 and 25 (ig/ml, respectively, without any cytotoxicity towards the cells [19,174,222]. 

The amino acid L-tyrosine is the starting material of melanin biosynthesis. The first step of melanogenesis is centered on tyrosinase (EC 1.14.18.1), a copper-containing glycoprotein. Until recently, this enzyme was believed to catalyze the hydroxylation of L-tyrosine... 

Artocarpus heterophylla Lamk. (bark) DieLs-Alder-type adducts Artonin C (401) artonin D (402) artonin I (397) (root bark). Prenyldihydrochalcone-chalcone dimers (Diels-Alder-type adducts) Artonin X (403) kuwanon R (404). Used as a traditional medicine in Southeastern Asia. Ingredient in the preparations of some Ayurvedic and Yunani medicines. Melanin biosynthesis inhibitory activity. Flano et al., 1990[251], 1992[252] Shinomiya et al., 1995[253]. 

The biosynthetic pathway for melanin formation, operating in insects, animals, and plants, has largely been elucidated by Raper [15], Mason [16], and Lerner et al. [17]. The first two steps in the pathway are the hydroxylation of monophenol to o-diphenol (monophenolase or cresolase activity) and the oxidation of diphenol to o-quinones (diphenolase or catecholase activity), both using molecular oxygen followed by a series of nonenzymatic steps resulting in the formation of melanin [15,18,19]. The whole pathway for melanin biosynthesis is shown in Scheme 1. 

Arung ET, Shimizu K, Kondo R (2006) Inhibitory effect of artocarpanone from Arto-carpus heterophyllus on melanin biosynthesis. Biol Pharm Bull 29(9) 1966-1969... 

Some anti-frmgal agents such as tricyclazole produce a weakening of cell walls by inhibiting melanin biosynthesis. More recently, several compounds that target the p-(l,3)-D-glucan and chitin synthases have been developed. 

These alkaloids inhibit melanin biosynthesis in B16 melanoma cells this represents a rare example of such inhibition by indole alkaloids. 

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