Melanin synthesis inhibitor

Lee CH, Chung MC, Lee HJ, Bae KS, Kho YH (1997) MR566A and MR566B, New Melanin Synthesis Inhibitors Produced by Trichoderma harzianum I. Taxonomy, Fermentation, Isolation and Biological Activities. J Antibiot 50 469... 

Compound 16 showed dose-dependent q totoxicity in a study of inhibition of melanin synthesis by melan-a cell hnes. The cellular survival rate was foimd to be low after treatment with 20 jtM of 16 [45]. Compound 11 inhibited melanin synthesis in the melan-a cells at a concentration of 10 p,M. The inhibition of melanin synthesis by 11 was found to be similar to that of phenylthiourea, which is a well-known melanin synthesis inhibitor [45]. The authors concluded that compound 11 is a new candidate for the development of depigmenting agents [45]. 

Further analysis of the UV spectrum revealed that this compound is a gallic acid derivative. A search of the Dictionary of Natural Products for molecular ion and plant genus name leads to the identification of a known compound - Pterocaryanin B. The compounds with poly-hydroxyl groups in their structures are very well known as tyrosinase inhibitors and are responsible for the inhibition of melanin synthesis. Therefore, no further isolation was necessary. 

Melanin synthesis of the arthropods is essential for defense and development. The melaniza-tion cascade is activated by bacterial PG or fungal /3-1,3-glucan. Lee and co-workers reported that the tetrasaccharide tetrapeptide functioned as a competitive inhibitor of the natural PG-induced melanization reaction [151]. By using a tetrasaccharide tetrapeptide-coupled column, the Tenebrio molitor PG recognition protein (Tm-PGRP) was purified without activation of the prophenoloxidase. 

Tyrosinase inhibitors, antioxidants and vitamins to block excess melanin synthesis... 

Hydroquinone is closely related to phenol and can reduce melanin production, ft appears that it can also degrade melanosomes. It has a tyrosinase-inhibiting activity and can change the membrane structure of the intracellular organelles of melanocytes. Hydroquinone acts mostly on the first stages of melanin synthesis. Its action is therefore gradual, like any tyrosinase inhibitor. 

Biochemical basis of hypopigmentation Phenylalanine is competitive inhibitor of tyrosinase (key enzyme in melanin synthesis)... 

Cucurbitacins D and R inhibited both tyrosinase activity and the melanin synthesis of B16/F10 melanoma cells. Of the two compounds, cucurbitacin D showed higher potency than either cucurbitacin R or the reference drug used in this experiment, with IC50 values of 0.18 pM as an inhibitor of tyrosinase activity and 0.16 pM as an inhibitor of melanin synthesis. Cucurbitacin R gave values of 6.7 and 7.5 pM while the reference drug hydroquinone gave values of 11.5 and 7.4 pM against tyrosinase activity and melanin synthesis, respectively [88]. 

Cha, S. H., Ko, S. C., Kim, D., and Jeon, Y. J. (2010). Screening of marine algae for potential tyrosinase inhibitor Those inhibitors reduced tyrosinase activity and melanin synthesis in zebrafish. /. Dermatol. 57,1-10. 

A case of bull s-eye maculopathy was reported in a 56-year-old woman who had been taking uva-ursi tea "regularly" (dose and frequency not reported) for 3 years. The woman reported a decrease in visual acuity in the third year. The reporting authors noted that hydroquinone compounds are known inhibitors of tyrosine kinase and thus melanin synthesis, and that decreased melanin in the eye might account for the maculopathy (Wang and Del Priore 2004). 

Further, owing to deamination, p-hydroxyphenylpyruvic acid (15), a well-known inhibitor of tyrosinase, was produced from tyrosine. This product underwent further transformation to yield biphenyl 16 while indolylpyruvic acid (22) and subsequently indole (19) were formed from tryptophan. Hence, in biological systems, the loss of the starting material, i.e. tyrosine, for melanin synthesis due to the formation of 15, 16 and 18 may be counteracted by tryptophan, as an alternative substrate in the pathway of melanogenesis through 22 and 19. However, such a replacement of substrate for melanin by tryptophan is not possible in... 

The first total synthesis of the dihydrobenzofuran ( )-linderal A, a potent inhibitor in melanin biosynthesis of cultured B-16 melanoma cell, was achieved via a 20-step reaction sequence starting from 4,6-dimethoxysalicylaldehyde <01OL1359>. 

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