Disease relevance of Dihydroxynaphthoquinone

• Screening results indicated that 1,4-diacetyl-6,7-dimethyl-4a,5,8,8a-tetrahydronaphthalene and 5,8-bis(benzoyloxy)-2,3-dimethyl-1,4-naphthoquinone possessed borderline activity against leukemia P388 and that naphthazarin diacetate possessed confirmed cytotoxicity against the cell culture of human epidermoid carcinoma of the nasopharynx [1].
• Inhibitory effect of a naphthazarin derivative, S64, on heat shock factor (Hsf) activation and glutathione status following hypoxia [2].
• Tricrozarin A exhibits antimicrobial activity against gram-positive bacteria, fungi, and yeast in vitro and is the first tetra-oxygenated naphthazarin derivative isolated from higher plants [3].
• The cytotoxicity of naphthazarin derivatives isolated from the roots of Onosma arenaria on human cervix adenocarcinoma cells (HeLa) and leukaemia K562 cells, as well on non-malignant peripheral blood mononuclear cells (PBMC) was studied [4].

High impact information on Dihydroxynaphthoquinone

• A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed [5].
• Although both cell types did undergo apoptosis when exposed to the lysosomotropic detergent MSDH, the redox-cycling quinone naphthazarin, or the protein kinase inhibitor staurosporine, I-cells exerted a markedly decreased response to these agonists than did normal fibroblasts [6].
• Guanabenz inhibited, the leakage of lysosomal cathepsin D to cytosol, the decreased mitochondrial potential, and the release of mitochondrial cytochrome c, which were induced by naphthazarin [7].
• We now report on a study into the protective effects of rilmenidine and AGN 192403, which have affinity for imidazoline-1 receptors, on the cytotoxicity induced by naphthazarin and inhibitors of mitochondrial respiration in astrocytes [8].
• Immunofluorescence analysis of the intracellular distribution of cathepsin D revealed a distinct granular pattern in control cells, whereas cells treated with naphthazarin for 30 min exhibited more diffuse staining that corresponded to release of the enzyme from lysosomes to the cytosol [9].

Biological context of Dihydroxynaphthoquinone

• Most of the cells displayed ultrastructure typical of apoptosis after 8 h of exposure to naphthazarin [9].
• The membrane-potential-sensitive probe JC-1 and flow cytometry did not detect a permanent decrease in mitochondrial transmembrane potential (delta psi(m)) until after 5 h of naphthazarin treatment [9].
• Comparative study on cytogenetic effects by diplatinum complexes of the ligands of naphthazarine and squaric acid in human lymphocytes [10].
• The rat heart myocytes were also exposed to the redox cycling substance naphthazarin (5, 8-dihydroxy-1,4-naphthoquinone) to induce oxidative stress [11].
• In this study, we showed that hypoxia induced a DNA-binding activity of Hsf and activation of hsp70 gene expression in colon cancer Clone A cells, and that a naphthazarin derivative, S64, significantly inhibited the hypoxia-inducible hsp70 gene expression in Clone A cells [2].

Anatomical context of Dihydroxynaphthoquinone

• Temporal aspects of cathepsin D relocalization, cytochrome c release, and decrease in mitochondrial transmembrane potential (delta psi(m)) were studied in myocytes exposed to the redox-cycling xenobiotic naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) [12].
• Immunofluorescence labeling revealed that cathepsin D was translocated to the cytosol after 30 minutes of naphthazarin treatment, and cytochrome c was released from mitochondria to the cytosol after 2 hours [12].
• A series of 2-substituted naphthazarin derivatives, 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives and 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives, were synthesized, and their cytotoxic activity against some cancer cell lines and antitumor action against S-180 tumor were evaluated [13].

Associations of Dihydroxynaphthoquinone with other chemical compounds

• Naphthazarin (5,8-dihydroxy-1,4-naphthoquinone), the basic unit of several tetracyclic antitumor antibiotics, and its glutathione conjugate were reduced by the one- and two-electron transfer flavoproteins NADPH-cytochrome P450 reductase and DT-diaphorase to their semi- and hydroquinone forms, respectively [14].
• Apoptosis was inhibited in rat cardiomyocytes pretreated with the aspartic protease inhibitor pepstatin A and subsequently exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) [15].
• The inhibitory activity is due in part to the redox cycling of naphthazarin with the concommitant transfer of reducing equivalents from NADPH to molecular oxygen, thus diverting electrons from cytochrome P-450 enzymes [16].
• Since both NADP and dicoumarol inhibited the naphthazarin-stimulated non-stoichiometric consumption of NADPH and oxygen then naphthazarin redox cycling probably involves both DT-diaphorase and NADPH cytochrome P-450 reductase [16].
• Conformational and electrostatic properties of naphthazarin, juglone, and naphthoquinone: an ab initio theoretical study [17].

Gene context of Dihydroxynaphthoquinone

• Our findings show that, during naphthazarin-induced apoptosis, lysosomal destabilization (measured as release of cathepsin D) precedes release of cytochrome c, loss of delta psi(m), and morphologic alterations [9].
• Autoxidation accompanied the DT-diaphorase and NADPH-cytochrome P450 reductase catalysis of naphthazarin and its glutathionyl adduct as well as the 1,4-reductive addition of GSH to naphthazarin [14].
• Superoxide dismutase at catalytic concentrations (nM range) enhanced slightly (1.1- to 1.6-fold) the autoxidation following the enzymatic catalysis of naphthazarin [14].
• Pepstatin A pretreatment did not prevent release of cathepsin D from lysosomes but did significantly inhibit subsequent naphthazarin-induced caspase activation and apoptotic morphology [15].
• Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1, 4-naphthoquinones [18].

Analytical, diagnostic and therapeutic context of Dihydroxynaphthoquinone

• The results of various spectroscopies on BN-3 suggest that M-92 components consisted of chromophores in which juglone (5-hydroxynaphthoquinone) is conjugated with naphthazarin (5,8-dihydroxynaphthoquinone) [19].
• FT Raman and FTIR spectra of Naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) and its deuterated analogue are recorded [20].

References