Metabolism / Metabolites
1,4-Dihydroxynaphthyl was produced in pigs, peas, Escherichia coli, and Desulfovibrio megaterium. /From Table/
5-Hydroxy-1,4-Naphthoquinone was produced in walnuts; 1,4-Naphthosemiquinone was produced in Escherichia coli. /From Table/
High-performance liquid chromatography-reduction electrochemical detection showed that 1-naphthol was converted to naphthoquinone metabolites in rat liver microsomes. At least two cytochrome P450-independent metabolic pathways were involved. Iron-dependent lipid peroxidation appears to at least partially contribute to the conversion of 1-naphthol to 1,4-naphthoquinone, while superoxide anion radicals generated by NADPH-cytochrome P450 reductase may also catalyze this conversion. Therefore, 1-naphthol appears to be converted to cytotoxic naphthoquinone metabolites via a mechanism dependent on free radical generation in rat liver microsomes. Carbonyl reductases, cytoplasmic monomeric oxidoreductases with broad specificity for carbonyl compounds, are the main NADPH-dependent quinone reductases in human liver, while DT-dihydroflavinase, the main two-electron-transfer quinone reductase in rat liver, contributes very little to quinone reductase activity in human liver. Carbonyl reductases provide the enzymatic basis for the reduction of a variety of natural and synthetic quinones. Generally, carbonyl groups located at chemically active sites (K-regions) are more easily reduced than those located at inert sites. The optimal substrates are K-region ortho-quinones of polycyclic aromatic hydrocarbons phenanthrene, pyrene, benzo[a]anthracene, and benzo[a]pyrene. …Non-K-region ortho-quinones, such as 1,2-naphthoquinone and 1,2-anthraquinone… are also optimal substrates. … For more complete metabolite/metabolite data on 1,4-naphthoquinone (9 metabolites in 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 is a yellow needle-like crystal or brownish-green powder with an odor similar to benzoquinone. (NTP, 1992)
1,4-Naphthoquinone is the parent structure of the 1,4-naphthoquinone family, in which the oxo groups of the quinone moiety are located at the 1 and 4 positions of the naphthalene ring. Its derivatives have pharmacological activity. It is derived from the hydride of naphthalene.
1,4-Naphthoquinone has been reported to be found in walnuts (Juglans regia) and black walnuts (Juglans nigra), and relevant data exist.
1,4-Naphthoquinone, or p-naphthoquinone, is an organic compound derived from naphthalene. Several isomers of naphthoquinone are known, the most famous of which is 1,2-naphthoquinone. 1,4-Naphthoquinone forms volatile yellow triclinic crystals with a pungent odor similar to benzoquinone. It is almost insoluble in cold water, slightly soluble in petroleum ether, and more readily soluble in polar organic solvents. In alkaline solutions, it appears reddish-brown. Vitamin K is a derivative of 1,4-naphthoquinone. It is a planar molecule consisting of an aromatic ring fused to a quinone subunit. Naphthalene is a component of aviation kerosene, diesel fuel, and cigarette smoke. It is also a byproduct of incomplete combustion and is therefore a ubiquitous environmental pollutant. Typical concentrations of naphthalene in urban air are approximately 0.18 ppb.
See also: …See more…

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Mechanism of Action
Quinones are α,β-unsaturated ketones that react with thiol groups. …Key biochemical damage…/involves/ the -SH groups of enzymes such as amylases and carboxylases, which are inhibited by quinones. The overall mechanism may involve enzymes binding to the quinone nucleus via substitution or addition on the double bond, oxidation reactions with the -SH group, and changes in redox potential. /Quinones/
The toxic mechanism of 1-naphthol to isolated rat hepatocytes is related to the formation of reactive oxygen species and the generation of oxidative stress. Dicoumarol enhances the cytotoxicity of 1-naphthol by inhibiting DT-dihydroflavinase and making more naphthoquinone metabolites available for redox cycling. Naphthoquinone Metabolites
This study used three structurally related naphthoquinone compounds: 1,4-naphthoquinone (1,4-NQ), 2-methyl-1,4-naphthoquinone, and 2,3-dimethyl-1,4-naphthoquinone (2,3-diMe-1,4-NQ) to explore the possible mechanisms by which naphthoquinones induce in vitro hepatocyte toxicity. The results showed that 1,4-NQ was more toxic than 2-Me-1,4-NQ, while 2,3-diMe-1,4-NQ did not induce cell death at the concentrations used (limited by solubility). All three naphthoquinones significantly reduced intracellular glutathione (GSH) levels. However, prior to cell death, GSH depletion induced by 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone was faster and more widespread than that induced by the non-toxic 2,3-dimethyl-1,4-naphthoquinone. Further studies have shown that 2,3-dimethyl-1,4-naphthoquinone is cytotoxic in the presence of dicumarol, which in turn enhances the cytotoxicity of both 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone. To investigate the differential cytotoxicity of these three naphthoquinones, we evaluated their redox cycling capacity and their ability to covalently bind to cellular nucleophiles. This study investigated redox cycling using rat liver microsomes, and the results showed that the order of naphthoquinone-stimulated redox cycling potency was: 1,4-naphthoquinone (1,4-NQ) > 2-methyl-1,4-naphthoquinone (2-Me-1,4-NQ) > 2,3-dimethyl-1,4-naphthoquinone (2,3-diMe-1,4-NQ), as confirmed by non-stoichiometric NADPH oxidation and oxygen consumption. NADPH-cytochrome P450 reductase is considered the major enzyme involved in naphthoquinone-stimulated redox cycling. The reactivity of naphthoquinone with glutathione (GSH), and consequently its reactivity with other nucleophiles, followed the order: 1,4-NQ > 2-Me-1,4-NQ, and significantly greater than 2,3-dimethyl-1,4-NQ. Overall, these studies indicate that 2,3-dimethyl-1,4-naphthoquinone (2,3-diMe-1,4-NQ) is non-cytotoxic (except in the presence of dicumarol), a non-toxicity possibly related to its weak redox cycling ability and/or inability to react directly with nucleophiles. We investigated the mechanisms by which quinones with varying reactivity alter mitochondrial membrane permeability. Rat liver mitochondria were incubated for 3 minutes with 0 to 10⁻³ mol (M) concentrations of menadione (MQ), 1,4-naphthoquinone (NQ), 1,4-benzenequinone (BQ), 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ), or 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ), followed by the addition of 0 or 20 μM calcium chloride. Calcium ion (Ca²⁺) release was monitored for 28 minutes. The effects on mitochondrial membrane polarization and mitochondrial swelling induction were determined. MQ, NQ, BQ, DiOMeNQ, and DiMeNQ all accumulated all added Ca²⁺, but subsequently released Ca²⁺ after a hysteresis period that shortened with increasing concentration. The concentrations that induced 50% Ca2+ release were: NQ, 1.6 μM; BQ, 5.3 μM; MQ, 41.6 μM; DiOMeNQ, 89.9 μM; and DiMeNQ, 232.7 μM. Ca2+ release was accompanied by membrane depolarization and mitochondrial swelling. Rat liver mitochondria were pretreated with 0.2 mmol potassium cyanide, followed by treatment with 0–10⁻³ M of NQ, BQ, MQ, DiOMeNQ, or DiMeNQ. The redox cycle activity of these compounds was assessed by measuring cyanide-insensitive oxygen consumption (CIOC). All compounds except BQ induced a concentration-dependent increase in CIOC. MQ, DiOMeNQ, and DiMeNQ induced similar CIOC rates at their respective Ca²⁺ release EC50 concentrations. BQ and NQ induced very low CIOCs at their respective EC50 concentrations. Rat liver mitochondria were pretreated with 0 or 400 nanomolar cyclosporine A (cycA) and then incubated with NQ, BQ, MQ, DiOMeNQ, or DiMeNQ at a Ca²⁺ release EC50 concentration. 70 μM calcium chloride was subsequently added. Cyclodextrin A completely inhibited the release of Ca²⁺ from naphthoquinone (NQ), menadione (MQ), dimethylnaphthoquinone (DiOMeNQ), and dimethylnaphthoquinone (DiMeNQ). Benzoquinone (BQ) accumulated very little before releasing Ca²⁺; however, cyclodextrin A slowed its release rate. The authors concluded that quinones capable of redox cycles (DiOMeNQ, DiMeNQ, MQ, and NQ) can increase mitochondrial membrane permeability by altering the regulation of cyclodextrin A-sensitive pores. Arylated quinones (such as BQ) alter mitochondrial membrane permeability by depolarizing the membrane. ...1,4-Naphthoquinone (the active metabolite of 1-naphthol) reacts with reducing agents (such as NADPH and glutathione) to generate semiquinone radicals, which can be detected by electron spin resonance spectroscopy. In the presence of glutathione as a reducing agent, both menadione and 1,4-naphthoquinone undergo net single-electron reduction and bind to glutathione. Under high glutathione concentrations, 1,4-naphthoquinone forms monoconjugated and diconjugated semiquinones. The naphthoquinone-glutathione conjugates should undergo redox cycles in a similar manner to the menadione conjugates. Semiquinone intermediates can only be detected under a nitrogen atmosphere; they are likely the main oxygen-reactive substances in the redox cycles of menadione and the 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.)