Metabolism / Metabolites
Yields 1,4-dihydroxynaphthalene in pig; in pea; in Escherichia coli; in desulfovibrio gigas. /From Table/
Yields 5-hydroxy-1,4-naphthoquinone in juglans; 1,4-naphthosemiquinone in Escherichia coli. /From Table/
By using HPLC with reductive electrochemical detection, it was shown that 1-naphthol is converted to naphthoquinone metabolites by rat liver microsomes. At least two metabolic pathways, independent of cytochrome p450, appear to be involved. Fe-dependent lipid peroxidation appears to be responsible for at least part of the conversion of 1-naphthol to predominantly 1,4-naphthoquinone, and it seems likely that superoxide anion radical generation by NADPH-cytochrome p450 reductase could also catalyze this conversion. 1-Naphthol therefore seems to be converted to cytotoxic naphthoquinone metabolites by mechanisms dependent upon the generation of free radicals in rat liver microsomes.
Carbonyl reductase, ... a cytosolic monomeric oxidoreductase of broad specificity for carbonyl compounds, was the main NADPH-dependent quinone reductase in human liver, whereas DT-diaphorase, the principal 2-electron-transferring quinone reductase in rat liver, contributed a very minor part to the quinone reductase activity of human liver. Carbonyl reductase provides the enzymic basis for the reduction of a great variety of natural and man-made quinones. Generally, oxo groups at chemically reactive positions (K-region) were more efficiently reduced than those at more inert positions. The best substrates were the K-region o-quinones of the polycyclic aromatic hydrocarbons phenanthrene, pyrene, benz(a)anthracene, and benzo(a)pyrene. ... non-K-region o-quinones, 1,2-naphthoquinone and 1,2-anthraquinone ... were the best substrates. ...
For more Metabolism/Metabolites (Complete) data for 1,4-NAPHTHOQUINONE (9 total), please visit the HSDB record page.

[1]. Beyond topoisomerase inhibition: antitumor 1,4-naphthoquinones as potential inhibitors of human monoamine oxidase. Chem Biol Drug Des. 2014 Apr;83(4):401-10.

1,4-naphthoquinone appears as yellow needles or brownish green powder with an odor of benzoquinone. (NTP, 1992)
1,4-naphthoquinone is the parent structure of the family of 1,4-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 4 of the naphthalene ring. Derivatives have pharmacological properties. It derives from a hydride of a naphthalene.
1,4-Naphthoquinone has been reported in Juglans regia and Juglans nigra with data available.
1,4-Naphthoquinone or para-naphthoquinone is an organic compound derived from naphthalene. Several isomeric naphthoquinones are known, notably 1,2-naphthoquinone. 1,4-Naphthoquinone forms volatile yellow triclinic crystals and has a sharp odor similar to benzoquinone. It is almost insoluble in cold water, slightly soluble in petroleum ether, and more soluble in polar organic solvents. In alkaline solutions it produces a reddish-brown color. Vitamin K is a derivative of 1,4-naphthoquinone. It is a planar molecule with one aromatic ring fused to a quinone subunit. Naphthalene is a constituent of jet fuel, diesel fuel and cigarette smoke. It is also a byproduct of incomplete combustion and hence is an ubiquitous environmental pollutant. The typical air concentration of naphthalene in cities is about 0.18 ppb.

See also: ... View More ...

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Mechanism of Action
Quinones are alpha-beta-unsaturated ketones & react with sulfhydryl groups. ... Critical biochem lesion ... /involves/ -SH groups of enzymes such as amylase & carboxylase which are inhibited by quinones. Overall mechanism may involve binding of enzyme to quinone nucleus by substitution or addition at the double bond, an oxidative reaction with -SH group, & change in redox potential. /Quinones/
The mechanism of the toxicity of 1-naphthol in isolated rat hepatocyte was related to the formation of active oxygen species and the creation of an oxidative stress. Dicoumarol potentiated the cytotoxicity of 1-naphthoI by inhibiting DT-diaphorase and making more naphthoquinone metabolites available for redox cycling. /Naphthoquinone metabolites/
The possible mechanisms of naphthoquinone-induced toxicity to isolated hepatocytes were investigated by using three structurally-related naphthoquinones, 1,4-naphthoquinone (1,4-NQ), 2-methyl-1,4-naphthoquinone, and 2,3-dimethyl-1,4-naphthoquinone (2,3-diMe-1,4-NQ). 1,4-NQ was more toxic than 2-Me-1,4-NQ whereas 2,3-diMe-1,4-NQ did not cause cell death solubility-limited concentrations used. All three naphthoquinones extensively depleted intracellular GSH. However, the depletion of GSH induced by 1,4-NQ and 2-Me-1,4-NQ prior to cell death was more rapid and extensive than that induced by the non-toxic 2,3-diMe-1,4-NQ. Further studies demonstrated that 2,3-diMe-1,4-NQ was cytotoxic in the presence of dicoumarol, a cmpd which also potentiates the cytotoxicity of 1,4-NQ and 2-Me-1,4-NQ. To investigate the differential cytotoxicity of these three naphthoquinones, their relative capacities to redox cycle and to bind covalently to cellular nucleophiles were assessed. Redox cycling was investigated by using rat liver microsomes where the order of potency for quinone-stimulated redox cycling was 1,4-NQ ... 2-Me-1,4-NQ ... and 2,3-diMe-1,4-NQ as indicated by non-stoichiometric amounts of NADPH oxidation and O consumption. NADPH-cytochrome p450 reductase was implicated as the enzyme primarily responsible for naphthoquinone-stimulated redox cycling. The reactivity of the naphthoquinones with GSH and, by implication, with other cellular nucleophiles was 1,4-NQ > 2-Me-1,4-NQ and much > 2,3-diMe-1,4-NQ. Overall, these studies indicate that 2,3-diMe-1,4-NQ is not cytotoxic (except in the presence of dicoumarol) and this lack of toxicity may be related either to its lesser capacity to redox cycle and/or its inability to react directly with cellular nucleophiles.
Mechanisms by which quinones of varying reactivity alter mitochondrial membrane permeability were examined. Rat liver mitochondria were incubated with 0 to 10-3 molar (M) menadione (MQ), 1,4-naphthoquinone (NQ), 1,4-benzoquinone (BQ), 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ), or 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ) for 3 minutes after which 0 or 20 uM calcium-chloride was added. Release of calcium-ion (Ca2+) was monitored for 28 minutes. The effects on the state of polarization of the mitochondrial membrane and induction of mitochondrial swelling were determined. MQ, NQ, BQ, DiOMeNQ, and DiMeNQ accumulated all of the added Ca2+, but then released it following a lag period which decreased with increasing concentration. The concentrations inducing 50% Ca2+ release were: NQ, 1.6 uM; BQ, 5.3 uM; MQ, 41.6 uM; DiOMeNQ, 89.9 uM; and DiMeNQ 232.7 uM. The release of Ca2+ was accompanied by depolarization of the membrane potential and induction of mitochondrial swelling. Rat liver mitochondria were pretreated with 0.2 millimolar potassium-cyanide, then treated with 0 to 10-3 M NQ, BQ, MQ, DiOMeNQ, or DiMeNQ. Redox recycling reactivity of the compounds was assessed by measuring the rates of cyanide insensitive oxygen consumption (CIOC). All compounds except BQ caused concentration dependent increases in CIOC. MQ, DiOMeNQ, and DiMeNQ at their EC50s for Ca2+ release induced similar rates of CIOC. BQ and NQ induced very little CIOC at their EC50s. Rat liver mitochondria were pretreated with 0 or 400 nanomolar cyclosporin-A (cycA) and then incubated with NQ, BQ, MQ, DiOMeNQ, or DiMeNQ at their EC50s for Ca2+ release. This was followed by addition of 70 uM calcium-chloride. CycA completely inhibited release of Ca2+ by NQ, MQ, DiOMeNQ, and DiMeNQ. BQ accumulated very little Ca2+ before releasing it; however, the rate of release was slowed by cycA. The authors conclude that quinones that can undergo redox recycling (DiOMeNQ, DiMeNQ, MQ, and NQ) can permeabilize mitochondrial membranes by altering regulation of cycA sensitive pores. Arylating quinones such as BQ alter mitochondrial membrane permeability by depolarizing the membrane.
...1,4-Naphthoquinone (a reactive metabolite of 1-naphthol) with reducing agents such as NADPH and glutathione led to the formation of semiquinone-free radicals, which were detected with electron spin resonance spectroscopy. In the presence of glutathione as a reducing agent, menadione and 1,4-naphthoquinone underwent net one-electron reduction and conjugation with glutathione. At higher concentrations of glutathione, 1,4-naphthoquinone formed the semiquinones of both the monoconjugate and the diconjugate. The naphthoquinone-glutathione conjugates should redox cycle in a manner already known for the menadione conjugate. The semiquinone intermediates could be detected only under a nitrogen atmosphere and are probably the primary oxygen-reactive species responsible for the redox cycling of menadione- and naphthoquinone-glutathione conjugates.

C₁₀H₆O₂

158.16

158.036

130-15-4

1,4-Naphthoquinone-d6;26473-08-5

8530

Light yellow to yellow solid powder

1.3±0.1 g/cm3

297.9±40.0 °C at 760 mmHg

119-122 °C(lit.)

111.2±24.3 °C

0.0±0.6 mmHg at 25°C

1.617

1.79

0

2

0

12

227

0

FRASJONUBLZVQX-UHFFFAOYSA-N

InChI=1S/C10H6O2/c11-9-5-6-10(12)8-4-2-1-3-7(8)9/h1-6H

naphthalene-1,4-dione

1,4Naphthoquinone; 1,4 Naphthoquinone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~632.27 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: 2.5 mg/mL (15.81 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (15.81 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)