Inhibitory effect of novel tetrahydropyrimidine-2(1H)-thiones on melanogenesis.

The series of imidazoldine-2-thiones 2 and tetrahydropyrimidine-2-thiones 3 were discovered as inhibitor of alpha-MSH-induced melanin production in melanoma B16 cells. The primary bioassay showed that 1-(4-ethylbenzyl)-tetrahydropyrimidine-2(1H)-thione 3e (>100% inhibition at 10 microM, IC(50)=1.2 microM) and 1-(4-tert-butylbenzyl)-tetrahydropyrimidine-2(1H)-thione 3f (>100% inhibition at 10 microM, IC(50)=0.76 microM) exhibited potent inhibitory effect against alpha-MSH-induced melanin production. Compounds 3 inhibit the biosynthesis of tyrosinase without affecting its catalytic activity in melanogenesis.

[1]  K. Kawai,et al.  Contact allergy to kojic acid in skin care products , 1995, Contact dermatitis.

[2]  Y. Mishima.  Molecular and biological control of melanogenesis through tyrosinase genes and intrinsic and extrinsic regulatory factors. , 1994, Pigment cell research.

[3]  M. Fukuda,et al.  Arbutin: mechanism of its depigmenting action in human melanocyte culture. , 1996, The Journal of pharmacology and experimental therapeutics.

[4]  F. García-Cánovas,et al.  Effect of L-ascorbic acid on the monophenolase activity of tyrosinase. , 1993, The Biochemical journal.

[5]  G. Prota.  Progress in the chemistry of melanins and related metabolites , 1988, Medicinal research reviews.

[6]  Francisco Solano,et al.  Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. , 2006, Pigment cell research.

[7]  M. Miranda,et al.  Inhibition of L-tyrosine-induced micronuclei production by phenylthiourea in human melanoma cells. , 1999, Mutation research.

[8]  M. Cava,et al.  Thionation reactions of lawesson's reagents , 1985 .

[9]  V. Hearing,et al.  Mammalian tyrosinase--the critical regulatory control point in melanocyte pigmentation. , 1987, The International journal of biochemistry.

[10]  E. Monzani,et al.  Inhibition of the catecholase activity of biomimetic dinuclear copper complexes by kojic acid , 2000, JBIC Journal of Biological Inorganic Chemistry.

[11]  K. Wakamatsu,et al.  Eumelanin biosynthesis is regulated by coordinate expression of tyrosinase and tyrosinase-related protein-1 genes. , 1993, Experimental cell research.

[12]  C. Dardonville,et al.  Synthesis and pharmacological studies of new hybrid derivatives of fentanyl active at the mu-opioid receptor and I2-imidazoline binding sites. , 2006, Bioorganic & medicinal chemistry.

[13]  E. Berardesca,et al.  Clinical and Instrumental Evaluation of Skin Improvement after Treatment with a New 50% Pyruvic Acid Peel , 2006, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[14]  Youngsoo Kim,et al.  Oxyresveratrol and Hydroxystilbene Compounds , 2002, The Journal of Biological Chemistry.

[15]  Tetsuro Ito,et al.  Inhibitory Effects of Resveratrol Derivatives from Dipterocarpaceae Plants on Tyrosinase Activity , 2003, Bioscience, biotechnology, and biochemistry.

[16]  H. Glatt,et al.  Inhibitors of mammalian melanocyte tyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. , 1999, Biochemical pharmacology.

[17]  S. H. Kang,et al.  Oxyresveratrol as the potent inhibitor on dopa oxidase activity of mushroom tyrosinase. , 1998, Biochemical and biophysical research communications.

[18]  S. Orlow,et al.  Degradation of tyrosinase induced by phenylthiourea occurs following Golgi maturation. , 2005, Pigment cell research.

[19]  S. Passi,et al.  Molecular basis of substrate and inhibitory specificity of tyrosinase: phenolic compounds , 1981, The British journal of dermatology.

[20]  Ikuko Miyazaki,et al.  Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease , 2009, Neurotoxicity Research.

[21]  Marc Criton,et al.  Analogues of N-hydroxy-N'-phenylthiourea and N-hydroxy-N'-phenylurea as inhibitors of tyrosinase and melanin formation. , 2008, Bioorganic & medicinal chemistry letters.

[22]  K. Vrana,et al.  Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase , 1998, Journal of neuroscience research.

[23]  Piotr Prokopowicz,et al.  Effective and mild method for preparation of optically active α-amino aldehydes via TEMPO oxidation , 1998 .