Disease relevance of HSDB 2037

• Effect of hydroxy substituent position on 1,4-naphthoquinone toxicity to rat hepatocytes [1].
• Red cells pretreated with DDC to inhibit cellular superoxide dismutase were found to be markedly sensitive to oxyhemoglobin destruction and hemolysis in the presence of NQ [2].
• All six nucleotides had high affinity for the title enzyme from Lactobacillus casei with Ki values ranging from 0.59 to 3.6 microM; the most effective compounds were the dimethyl quinone 6 and the naphthoquinone 8 [3].
• 1-Naphthol, 1,2- and 1,4-naphthoquinone were also toxic to two human colonic adenocarcinoma cell lines, LoVo and COLO 206 [4].
• On the basis of the observation that nitrate reductase from Escherichia coli is sensitive to UV irradiation with an action spectrum indicative of a naphthoquinone (F. Brito and M. Dubourdieu, Biochem. Int. 15:1079-1088, 1987), we extracted and characterized quinone components from two different preparations of purified nitrate reductase [5].

High impact information on HSDB 2037

• Whereas the tetraketide carries an unmodified aromatic chromophore, the penta- through decaketides have undergone oxidative cyclization to the naphthoquinone, suggesting that this modification occurs during, not after, PKS assembly [6].
• The trypanosomatid flavoprotein disulfide reductase, trypanothione reductase, is shown to catalyze one-electron reduction of suitably substituted naphthoquinone and nitrofuran derivatives [7].
• They were functionally expressed in yeast COQ2 disruptant and showed a strict substrate specificity for geranyl diphosphate as the prenyl donor, in contrast to ubiquinone biosynthetic enzymes, suggesting that they are involved in the biosynthesis of shikonin, a naphthoquinone secondary metabolite [8].
• The doubling time of the menB26 mutant cells, but not the menA mutant cells, approaches the wild type when the growth medium is supplemented with naphthoquinone (NQ) derivatives such as 2-CO(2)H-1,4-NQ and 2-CH(3)-1,4-NQ [9].
• In this report, we investigate whether the NF-kappaB signaling pathway is blocked during apoptosis induced by 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (NA), an analog of naphthoquinone [10].

Chemical compound and disease context of HSDB 2037

• It was concluded that 5,8-dihydroxy-1,4-naphthoquinone toxicity is due to free radical formation, whereas the toxicity of 1,4-naphthoquinone and of 5-hydroxy-1,4-naphthoquinone also has an electrophilic addition component [1].
• Treatment of the hepatocytes with BSO (buthionine sulfoximine) or BCNU (1,3-bis-2-chloroethyl-1-nitrosourea) increased 5-hydroxy-1, 4-naphthoquinone and 5,8-dihydroxy-1,4-naphthoquinone toxicity, whereas neither BSO nor BCNU largely affected 1,4-naphthoquinone and 2-hydroxy-1, 4-naphthoquinone toxicity [1].
• The adducted protein formation may imply that naphthalene produces its in vivo toxicity through 1,2- and 1,4-naphthoquinone metabolites reacting with biomolecular proteins [11].
• The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl-1,4-naphthoquinone (MNQ), 1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes [12].
• A Gene Cluster for Prenylated Naphthoquinone and Prenylated Phenazine Biosynthesis in Streptomyces cinnamonensis DSM 1042 [13].

Biological context of HSDB 2037

• Our results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma GCS-HS gene and the subsequent elevation in gamma GCS activity [14].
• No evidence for lipid peroxidation was obtained for red cells treated with NQ either in the presence or the absence of DDC [2].
• Nanomolar NQ is shown to enhance the association of [3H]ryanodine for its high-affinity binding site and directly enhance channel-open probability in bilayer lipid membrane in a reversible manner [15].
• A naphthoquinone derivative, shikonin, has insulin-like actions by inhibiting both phosphatase and tensin homolog deleted on chromosome 10 and tyrosine phosphatases [16].
• The 1,4-naphthoquinone derivative, shikonin, has been shown to increase glucose uptake by adipocytes and myocytes with minor effects on protein tyrosine phosphorylation in the cells (Biochem Biophys Res Commun 292:642-651, 2002) [16].

Anatomical context of HSDB 2037

• This toxic effect is believed to result from oxidative damage to erythrocytes by "active oxygen" species formed via one-electron reduction of the naphthoquinone by oxyhaemoglobin [17].
• The study provides evidence that by its reactivity with essential thiol groups 1,4-naphthoquinone (1,4-NQ) prevents the assembly of a functional NADPH-oxidase in the neutrophil membrane [18].
• We also found that naphthoquinones, including 1,2-naphthoquinone, inhibit PTEN in the cell-free system, which suggested that the effect on PTEN (and thus the effect on phosphatidylinositol 3-kinase signaling) should be taken into account when examining the pharmacological actions of naphthoquinone derivatives [16].
• Almost all the naphthoquinone esters that contain a C-3 hydroxy group showed significant cytotoxicities against KB, HeLa, and HepG2 cell lines [19].
• A new naphthoquinone, isolated from the alcoholic extract of Psychotria rubra, exhibited significant cytotoxicity in the KB cell assay (ED50 = 3.0 micrograms/mL) [20].

Associations of HSDB 2037 with other chemical compounds

• EGF-receptor interaction is also significantly modulated by 1,4-naphthoquinone, 1,4-benzoquinone, and phenanthrenequinone but not by other quinones of anthracyclic antibiotics [21].
• Caspase-3-mediated cleavage of the NF-kappa B subunit p65 at the NH2 terminus potentiates naphthoquinone analog-induced apoptosis [10].
• Aqueous leaf extracts from Dionaea muscipula contain quinones such as the naphthoquinone plumbagin that couple to different NADH-dependent diaphorases, producing superoxide and hydrogen peroxide upon autoxidation [22].
• Electron spin resonance (ESR) spectroscopy was used to visualize the one-electron reduction products of 4-nitropyridine-N-oxide (4NPO), 1,4-naphthoquinone (1,4NQ), and dichlorophenolindolphenol (DCPIP) [23].
• Single topical applications of 1,4-naphthoquinone and its 5-hydroxy analog (juglone) produced dose-dependent increases in epidermal ODC activity in the dose range 880-3520 nmol/mouse [24].

Gene context of HSDB 2037

• METHODS: We used a novel and potent Cdc25A inhibitor, 2,3-bis-[2-hydroxyethylsulfonyl]-[1,4] naphthoquinone (NSC 95397), and its congener (2-mercaptoethanol)-3-methyl-1, 4-naphthoquinone (NSC 672121) to study the role of Cdc25A on the MAPK pathway in human prostate cancer cells [25].
• We now show that deletion of either napG or napH almost abolished Nap-dependent nitrate reduction by strains defective in naphthoquinone synthesis [26].
• 58C80 [2-(4-t-butylcyclohexyl)-3-hydroxy-1,4-naphthoquinone] is an experimental naphthoquinone antimalarial drug which undergoes extensive alkyl hydroxylation to a single t-butylhydroxy metabolite in man in vivo and also in human liver microsomes, where this is catalysed primarily by a 54 kDa CYP2C9 form of cytochrome P450, P450hB20-27 [27].
• Induction of p73beta by a naphthoquinone analog is mediated by E2F-1 and triggers apoptosis in HeLa cells [28].
• 1,4-Naphthoquinone and four minor unknown metabolites from 1-naphthol were observed, and CYP1A2 and 2D6*1 were identified as the most active isoforms for the production of 1,4-naphthoquinone [29].

Analytical, diagnostic and therapeutic context of HSDB 2037

• Further studies revealed that 3b rapidly decomposes to the nucleotide in cell culture medium, suggesting that the naphthoquinone analogue is not sufficiently stable to function as a nucleotide prodrug [30].
• Structural analysis of naphthoquinone protein adducts with liquid chromatography/tandem mass spectrometry and the scoring algorithm for spectral analysis (SALSA) [11].
• The naphthoquinone or vanadate-activated PtdIns kinase activity could be isolated by antiphosphotyrosine antibody-agarose affinity chromatography [31].
• The relative reactivities of various naphthoquinone isomers (1,4-, 1,2- and 2-methyl-1,4-naphthoquinone) to two test proteins, apomyoglobin and human hemoglobin, were evaluated via liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) [11].
• METHODS: Introduction of 2 (trans-4[4 chlorophenol] cyclohexy[3-hydroxy-1, 4 naphthoquinone] (HNPQ) an experimental antiparasitic compound previously used only in adult HIV clinical trials, was instituted in the child and rapid oral desensitization to pyrimethamine was initiated in the adult patient [32].

References