Potent inhibitory effects of N-aryl S-alkylthiocarbamate derivatives on the dopa oxidase activity of mushroom tyrosinase.
ABSTRACT This study reports the potent inhibitory effect of N-aryl S-alkylthiocarbamate derivatives on mushroom tyrosinase (MT) activity. N-Aryl S-alkylthiocarbamate derivatives were found to exhibit a potent inhibitory effect on the dopa (3,4-dihydroxyphenylalanine) oxidase activity of mushroom tyrosinase. Most of the N-aryl S-alkylthiocarbamate derivatives (compounds from A to J) exhibited higher inhibitory effects than kojic acid (IC50=318 microM), a well known tyrosinase inhibitor. Tyrosinase was the most inhibited by S-phenetyl N-phenylthiocarbamate (compound E, IC50=7.25 microM), and this inhibition was 44 times stronger than that of kojic acid. Compound E exhibited 95.0% of inhibition at 100 microM. A kinetic study of MT inhibition by compound E using the Lineweaver-Burk plots analysis was performed. And the kinetics profiles observed suggest that compound E competitively inhibits MT.
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ABSTRACT: Tyrosinase is an enzyme having two copper atoms at the reactive site occurring in prokaryotic and eukaryotic organisms. In animals tyrosinase is responsible for pigmentation, in plants for protection of injured tissues or, as in fungi, to harden cell walls. Some of us have previously shown that tyrosinase is involved in truffle development and differentiation. Here we present the purification, the molecular properties and the reversible inhibition of Tuber melanosporum tyrosinase by dimethyl-sulfide and bis[methylthio]methane, the main flavour compounds of black and whitish truffles. The MW(r) is 39000. L-3,4-dihydroxyphenylalanine and L-tyrosine stain corresponding bands as expected for a true tyrosinase. Phenylthiourea, diethyldithiocarbamate and mimosine inhibit L-tyrosine and L-3,4-dihydroxyphenylalanine oxidation.FEMS Microbiology Letters 04/2003; 220(1):81-8. · 2.05 Impact Factor
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ABSTRACT: Several N-alkyl-Se-alkylselenocarbamates were prepared. The structure was confirmed by X-ray diffraction. N-Alkyl-Se-alkylselenocarbamates showed interesting NMR spectral features in (13)C and (77)Se NMR. They could be explained by the equilibrium between the major s-trans and the minor s-cis forms. This assumption was confirmed by the theoretical calculations.The Journal of Organic Chemistry 02/2002; 67(2):486-90. · 4.56 Impact Factor
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ABSTRACT: The herbicide S-ethyl N,N-dipropylthiocarbamate (EPTC) and three of its candidate metabolites (the sulfoxide, N-depropyl and S-methyl derivatives) inhibit mitochondrial low-Km aldehyde dehydrogenase (ALDH) in liver by 56 to 82% 2 hr after these thiocarbamates are administered intraperitoneally (ip) to mice at 8 mg/kg. They also greatly elevate the acetaldehyde level (determined as the O-benzyloxime ether) in blood (up to 500 microM) and brain (up to 3 ppm) 30 min after two ip treatments, the first with the thiocarbamate at 40 mg/kg and 2 hr later with ethanol at 1000 mg/kg. EPTC at 4 mg/kg inhibits liver ALDH activity by 50% and at 8 and 18 mg/kg gives half of the maximum ethanol-dependent elevation of acetaldehyde levels in blood and brain, respectively. The in vivo effects of other thiocarbamate herbicides at 8 mg/kg on ALDH activity and 40 mg/kg on acetaldehyde levels decrease in the order of thiobencarb, pebulate, vernolate and molinate > butylate and triallate > cycloate. The percentage inhibition of liver ALDH activity generally correlates with the elevation in blood and brain acetaldehyde under these treatment protocols. B.W. Hart and M.D. Faiman (Biochem. Pharmacol. 43 403-406, 1992) have shown that the alcohol-aversion drug disulfiram is metabolized to S-methyl N,N-diethylthiocarbamate and its sulfoxide as the penultimate and ultimate metabolites inhibiting ALDH. Thus, the thiocarbamate herbicides and their metabolites are similar to the disulfiram metabolites not only in homologous structure but also in their potency range as ALDH inhibitors in vivo. On this basis some of the thiocarbamate herbicides may sensitize agricultural workers to ethanol intoxication.Life Sciences 01/1994; 55(20):1537-44. · 2.56 Impact Factor