Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytotoxic activities of three new synthetic catechol analogues, beta-[(p-hydroxyphenyl)amino]alanine (Compound 1), N delta-(p-hydroxyphenyl)ornithine (Compound 2), and N delta-(m-hydroxyphenyl)ornithine (Compound 3), were determined against 10 human melanoma and 5 nonmelanoma cell lines. Activities of L-DOPA and 3,4-dihydroxybenzylamine were also measured. Dose-response curves were obtained and concentrations in micrograms/ml required to give 90% inhibition of colony formation (IC90) were calculated. Using a cutoff IC90 of less than 2.5 as a definition of activity. Compound 2 was active in 6 of 10 melanoma and 0 of 5 nonmelanoma cell lines while both Compound 1 and L-DOPA methyl ester were active in 1 of 10 melanomas and 0 of 5 nonmelanomas. Compound 3 was inactive in all cell lines and all IC90 values exceeded 100. 3,4-Dihydroxybenzylamine was active in 3 of 8 melanomas and 1 of 5 nonmelanomas. Regression analysis of IC90 values for Compound 2 and tyrosinase levels in the 15 cell lines yielded a correlation coefficient of 0.93 (P less than 0.001). By contrast, a similar analysis for 3,4-dihydroxybenzylamine gave a correlation coefficient of 0.17 (P greater than 0.05). Spectrophotometric data indicated that Compounds 1 and 2 were oxidized by tyrosinase to quinones. Cytotoxic activity was blocked by the tyrosinase inhibitor phenylthiocarbamide. Since the rates of activation of Compounds 1 and 2 were identical, the higher activity of Compound 2 was probably due to its higher lipophilicity and greater intracellular accumulation. Compounds 1 and 2 exhibited greater potency and selectivity against malignant melanoma than did the natural product L-DOPA methyl ester.
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PMID:Structure-activity relationships defining the cytotoxicity of catechol analogues against human malignant melanoma. 313 17

Agents were designed to exploit the high tyrosinase activity in melanotic melanoma relative to normal tissues. If specific tyrosinase activation of these agents occurred, the production of toxic metabolites in the melanoma cells would produce selective cell kill. Synthesis and antitumor activities of three new amino acids, 1a [beta-[(p-hydroxyphenyl)amino]alanine hydrochloride], 1b [N delta-(p-hydroxyphenyl)ornithine hydrochloride], and 1c [N delta-(m-hydroxyphenyl)ornithine dihydrochloride], were described. Compounds 1a and 1b were approximately 2-fold more active against the B-16 melanotic melanoma than the amelanotic melanoma cell line in vitro. Compound 1b was approximately 2-fold more potent than compound 1a against either cll line and was 8-fold more potent than L-glutamic acid gamma-(4-hydroxyanilide), a natural product isolated from mushroom. No significant growth inhibitory activity was found for the m-hydroxy analogue 1c at 100 micrometers, the highest concentration tested. Similarly, compound 1b exhibited better activity against P-388 (ED50 = 9.5 x 10(-6) M) than 1a (ED50 = 3.2 x 10(-5) M) and was about 30-fold more potent than 1c. Against human epidermoid carcinoma of the nasopharynx (KB), these agents showed modest inhibitory activity with ED50 values in the range of 1.2 to 3 x 10(-4) M. No in vivo activity against P-388 and B-16 at doses up to 150-200 mg/kg was observed. The biological results suggest that a nonspecific oxidation rather than a specific tyrosinase activation is involved in the biological action of these new compounds.
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PMID:Agents with potential specificity against melanotic melanoma. 708 35

1. Intermediates in the process of melanin synthesis formed through oxidation of catechols by tyrosinase produced the inactivation of ornithine decarboxylase (ODC), a key enzyme in the polyamine biosynthesis pathway. 2. The inactivation was dependent on the substrate used (dihydroxybenzylamine > L-3,4-dihydroxyphenylalanine > L-tyrosine) and on the concentration of intermediate produced rather than on the rate of formation. 3. Sulfhydryl compounds (dithiothreitol and glutathione) or quinone-reducing agents (ascorbic acid) prevented the inactivation of ODC; L-ornithine, but not other amino acids, also protected partially ODC. The results suggest that different cysteine residues in ODC molecule are implicated in the inactivatory event. 4. When 14C-labeled catechols were used, numerous polypeptides resulted labeled, showing that the reactive quinones formed as intermediates in the process of melanin biosynthesis bind covalently to many cellular proteins.
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PMID:Inactivation of ornithine decarboxylase by intermediates of tyrosinase-catalyzed reaction. 846 26

Plant secondary compounds have been documented to be deleterious to insects and other herbivores in diverse ways. In this study, the effect of catechol (phenolics), gramine (alkaloid) and L-ornithine-HCI (non-protein amino acid) on the activities of xenobiotic metabolizing enzymes in English grain aphid, Sitobion avenae, was evaluated. Phase I enzymes investigated in this study included carboxylesterase (CarE), and oxidoreductase, whereas Phase II enzymes were represented by glutathione S-transferase (GST). In general, CarE and GST activities in S. avenae were positively correlated with the concentration of plant secondary compounds in artificial diets. Oxidoreductase activity, however, displayed a different profile. Specifically, peroxidase (POD) and polyphenol oxidase (PPO) activities in S. avenae were positively correlated with concentrations of dietary catechol and gramine, respectively, whereas catalase (CAT) activity was significantly suppressed by the higher concentration of catechol, gramine and L-ornithine-HCl. These combined results suggest that CarE and GST in S. avenae are key enzymes to breakdown a broad spectrum of plant secondary compounds, whereas oxidoreductase, including PPO and POD, degrades specific groups of plant secondary compounds.
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PMID:Xenobiotic metabolism of plant secondary compounds in the English grain aphid, Sitobion avenae (F.) (Hemiptera: Aphididae). 2514 34