Disease relevance of Ursol ERN

• We also demonstrated that 1-naphthol UDP glucuronosyltransferase (EC 2.4.1.17) activity could be used to assess microsomal intactness in cases of type 1a glycogen storage disease, where mannose-6 phosphatase activity cannot be used [1].
• Selective toxicity of 1-naphthol to human colorectal tumour tissue [2].
• A hydrolase constitutively expressed in Pseudomonas aeruginosa which converts carbaryl to 1-naphthol was purified 1,767-fold by using a combination of anion-exchange, hydroxylapatite, gel filtration, and hydrophobic interaction chromatography techniques [3].
• Cell lines derived from human colonic adenocarcinomas metabolised 1-naphthol almost exclusively to its glucuronic acid conjugate [4].
• Saturation mutagenesis of toluene ortho-monooxygenase of Burkholderia cepacia G4 for Enhanced 1-naphthol synthesis and chloroform degradation [5].

High impact information on Ursol ERN

• Using this model, we demonstrated that choroid plexuses can act as an absolute blood-CSF barrier toward 1-naphthol, a cytotoxic, lipophilic model compound, by a coupled metabolism-efflux mechanism [6].
• In the case of UGT1A9, however, glucuronidation of alpha-naphthol and scopoletin was resistant to such inhibition, whereas glucuronidation of entacapone and several other aglycones was sensitive [7].
• The identity of the trapped radical could not be identified on the basis of published hyperfine coupling constants, but the observation that horseradish peroxidase-catalyzed oxidation of 1-naphthol produced an identical ESR signal suggests that the radical was either a phenoxy or phenoxy-derived radical [8].
• In cultured cells, the 1 hour turnover of 1 microM 1-naphthol to its glucuronide and sulphate conjugates averaged 35% and 8% respectively [9].
• Conjugation of 1-naphthol in human gastric epithelial cells [9].

Chemical compound and disease context of Ursol ERN

• The mechanism(s) of toxicity of 1-naphthol and two of its possible metabolites, 1,2- and 1,4-naphthoquinone, to freshly isolated rat hepatocytes has been studied [10].
• Pseudomonas sp. strain C4 metabolizes carbaryl (1-naphthyl-N-methylcarbamate) as the sole source of carbon and energy via 1-naphthol, 1,2-dihydroxynaphthalene, and gentisate [11].
• Evidence for an arene oxide-NIH shift pathway in the transformation of naphthalene to 1-naphthol by Bacillus cereus [12].
• In contrast, Pseudomonas sp. (NCIB 12043) was selected in a soil perfusion column enrichment at pH 5.2 and metabolized carbaryl rapidly to 1-naphthol and methylamine [13].

Biological context of Ursol ERN

• Our results show that the (metabolic) activation of 1-naphthol to 1,4-naphthoquinone by reaction with H2O2 from the oxidative burst is a necessary event for the inhibition to occur [14].
• Incubation of cells with 0.5 mM dihydrodiol, 1-naphthol, or 1,2-naphthoquinone decreased cell viability to an extent similar to that produced by 0.5 mM naphthalene [15].
• Reaction products of 1-naphthol with reactive oxygen species prevent NADPH oxidase activation in activated human neutrophils, but leave phagocytosis intact [14].
• Upon treatment with the enzyme, the Z-val-cit-p-amidobenzyl ether of 1-naphthol (2) underwent peptide bond hydrolysis with the rapid release of 1-naphthol [16].
• We have used this method to examine the kinetics of sulphation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells [17].

Anatomical context of Ursol ERN

• Conjugation of 1-naphthol was observed with both freshly isolated and cultured cells [9].
• The alpha-naphthol acetate esterases (ANAE) and diisopropyl-fluorophosphate (DFP)-binding proteins of NK cells, YAC cells and NK-YAC conjugates have been examined [18].
• Ketoprofen acylglucuronide irreversibly inhibited the glucuronidation of 1-naphthol and 2-naphthol catalyzed by human liver microsomes or by the recombinant rat liver isoform, UGT2B1, which is the main isoform involved in the glucuronidation of the drug [19].
• The established recombinant V79 cell lines stably expressed the UDP-glucuronosyltransferase activities towards 1-naphthol (HLUGP1) and hyodeoxycholic acid (HLUG25) at levels 10-20-fold higher than with transient expression, and in the range found in human liver [20].
• Activation of human neutrophils with opsonized particles in the presence of a nontoxic dose of 1-naphthol resulted in inhibition of superoxide anion production but not of the phagocytotic activity of the cells [14].

Associations of Ursol ERN with other chemical compounds

• Moreover, the glucuronidation of 1-naphthol and 4-nitrophenol was higher in "native" microsomes from male control rats than in those from female controls [21].
• Purification of these residues by thin-layer chromatography and further analysis by gas chromatography-mass spectrometry indicated that cis-1,2-dihydroxy-1,2-dihydronaphthalene, 1-naphthol, salicylic acid, and catechol were metabolites of naphthalene [22].
• However, significant increases of the rate of glucuronidation of 1-naphthol by Clophen A50 and of testosterone by both Clophen A50 and beta-naphthoflavone were only determined when the activities were measured in digitonin activated microsomes [23].
• UGT activity towards 4-methylumbelliferone and 1-naphthol was also detectable in oropharyngeal mucosa [24].
• The indole derivatives did not affect glutathione S-transferase activity and sulfation of 1-naphthol in either rat or monkey hepatocytes [25].

Gene context of Ursol ERN

• The metabolism of dihydrodiol by P450 isoforms was lower than that of 1-naphthol [26].
• Catalytic activity of UGT1A01 was determined with 7-hydroxy-4-(trifluoromethyl)-coumarin and more specific human UGT1A1 substrates (1-naphthol, beta-estradiol, 17 alpha-ethinylestradiol, and bilirubin) [27].
• Whereas activity of amino sulfotransferase (substrate 2-naphthylamine) decreased continuously during the entire culture period, the activity of phenol sulfotransferase (substrate 1-naphthol) decreased only slowly [28].
• Leukemic cells in the peripheral blood and bone marrow were monoblasts positive for alpha-naphthol butyrate esterase (alpha-NBE) staining, CD11c and CD36 antigens, whereas tumor cells in the pleural effusion were ATL cells positive for CD2, CD4, CD25, CD29 and CD45RA antigens [29].
• Coffee was also found to inhibit sulfotransferase (SULT) activity towards 1-naphthol in vitro to a similar extent (IC50=5.1%) as in intact Caco-2 cells, but exhibited no effect upon UDP-glucuronosyl transferase (UGT) activity in vitro [30].

Analytical, diagnostic and therapeutic context of Ursol ERN

• 1-Naphthol was selectively toxic to human colorectal tumours compared to corresponding normal colonic tissue removed at surgery and maintained in short-term organ culture [2].
• Cells were incubated in the presence of several concentrations of 1(14C)-naphthol, and formation of 1-naphthol glucuronide and 1-naphthol sulphate was assessed at various times by thin layer chromatography [31].
• In monkey cells BII only enhanced DTD, and no changes were observed in the glucuronidation of 1-naphthol after treatment with either DIM or BII [25].
• Conjugation of 1-naphthol by human bronchus and bronchoscopy samples [32].
• The lack of effect of BSO on 1-naphthol and 1,4-NQ is not easily explained but if one also considers the modest potentiation of cytotoxicity+ achieved with the other agents studied, the potential use of BSO in combined chemotherapy is at best rather modest [33].

References