Related Quinones Research Articles

Monoamine oxidase inhibitory naphthoquinone and/or naphthalene dimers from Lemuni Hitam (Diospyros sp.), a Malaysian herbal medicine.

From the extract of a Malaysian herbal medicine, Lemuni Hitam (Diospyros sp.), which exhibited monoamine oxidase (MAO) inhibition, three new naphthoquinone and/or naphthalene dimers (lemuninols A-C, 1-3) were isolated together with 4,6-dihydroxy-5-methoxy-2-methyl-naphthalene (8) and six known monomers (4-7, 9 and 10). The structures were determined by spectroscopic methods including 2D-NMR techniques. Among them, lemuninol A showed 45% inhibition of MAO (mouse liver) at 5.0 x 10(-6) g/ml, and lemuninols B and C and a naphthoquinone (9) indicated weak activity. Some related quinones were also tested for their MAO inhibitory activities.

Total synthesis of maesanin and analogues

An efficient total synthesis of maesanin and related quinones is reported, through direct alkylation of 1,2,4,5-tetramethoxybenzene with alkylbromides, followed by oxidation with ceric ammonium nitrate (CAN) which provokes formation of the quinone and deprotection of the more hindered methyl ether in one step, to furnish the desired 2-hydroxy-5-methoxy-1,4-benzoquinones 1a-h.

Cytotoxicity of 2- tert-butyl hydroquinone glutathione conjugates after apical and basolateral exposure of rat renal proximal tubular cell monolayers

Confluent monolayers of renal proximal tubular (RPT) cells cultured on porous supports were used to investigate the cytotoxicity induced by glutathione conjugates of 2- tert-butyl-(1,4)-hydroquinone (SG-TBHQ) after apical and basolateral exposure. As judged from lactate dehydrogenase (LDH) leakage, cytotoxicity was observed after basolateral exposure of monolayers to 250 and 500 μ m 2- tert-butyl-5-(glutathion- S-yl)hydroquinone (5SG-TBHQ). In these experiments, LDH leakage was 22.3 ± 1.9 and 32.2 ± 1.9%, respectively. Basolateral exposure of monolayers to 250 and 500 μ m 6SG-TBHQ resulted in LDH leakage of 22.2 ± 2.5 and 30.0 ± 2.7%, respectively. The double conjugate, 2- tert-butyl-3,6-(diglutathione- S-yl)hydroquinone (3,6SG-TBHQ), was not toxic and LDH leakage was about control level (15.0%). Basolaterally located probenecid-sensitive organic anion transporters did not seem to play a part in the cytotoxic effect. However, when RPT cell monolayers were cultured in 24-well tissue culture plates, apical challenge with 250 μ m 5SG-TBHQ induced a cytotoxic effect. In these experiments, LDH leakage was 33.5 ± 0.6%. With these cells, inhibition of apical γ-glutamyltranspeptidase (γGT) activity by acivicin, which was not toxic by itself, decreased 5SG-TBHQ-induced LDH leakage to 19.3 ± 1.2%, whereas 6SG-TBHQ (also 250μ m)-induced LDH leakage was increased to 55.3 ± 1.0%. Co-incubation of RPT cells with SG-TBHQs in the presence of 1.5 m m ascorbic acid (AA) pointed to a pro-oxidant rather than an antioxidant effect of AA. Superoxide dismutase and catalase completely abolished SG-TBHQ-induced cytotoxicity. Since cultured RPT cells lack N-acetylation of cysteine conjugates, the N-deacetylation/ N-acetylation ratio cannot have a vital role in renal toxicity of quinone thioethers in this in vitro system. It seems, therefore, that the cytotoxicity observed is mainly the result of extracellular redox cycling of SG-TBHQs. The lack of toxicity of 6SG-TBHQ after apical exposure could be due to detoxification by γGT-mediated cysteinylglycine- or cysteine-conjugate formation followed by cyclization, as shown for other related quinone glutathione conjugates. The relative importance of the observed effects for the in vivo situation is discussed.

5358699 Precious metal recovery process from carbonaceous ores

The antimicrobial activity against two bacterial strains and three fungi of five terpenoid quinones, three related quinones, and a quinone-containing essential oil was investigated by broth dilution and by agar vapor and box vapor assays. All the quinones, except for coenzyme Q10, exhibited their highest activity against Trichophyton mentagrophytes. Thymoquinone showed the most potent activity, not only by solution contact but also by vapor contact, with menadione the next most potent. Alizarin showed high activity only by solution contact. The antibacterial activity was related to the orthoquinone structure (1,2-chloranil and 1,2-naphthoquinone) and the antifungal activity was related to the paraquinone structure (chloranil, ubiquinone 0, thymoquinone, and menadione).

Role of thiol homeostasis and adenine nucleotide metabolism in the protective effects of fructose in quinone-induced cytotoxicity in rat hepatocytes

Freshly-isolated rat hepatocytes were exposed in glucose (15 mM) or fructose (5 mM) medium to menadione (2-methyl-1,4-naphthoquinone) (85 μM) or 1,4-naphthoquinone (NQ) (50 μM). Menadione and NQ are closely related quinones and have an approximately equal potential to induce redox cycling. However, NQ has a higher potential to arylate and is more toxic than menadione. During 2 hr of incubation, cell viability, thiol status, adenine nucleotide level and lactate production were determined. LDH-leakagewas used as a measure of cell viability. In glucose medium, exposure of hepatocytes to menadione or NQ resulted in a faster excretion rate of oxidised glutathione as compared to those cells in fructose medium. As a result, quinone-exposed hepatocytes in fructose medium retained higher amounts of oxidised glutathione. Menadione-exposed hepatocytes in fructose medium exhibited a diminished rate of transthiolation of protein thiols with oxidised glutathione as compared to those cells in glucose medium. The adenine nucleotide level of hepatocytes in glucose medium was markedly higher than in fructose medium. This was caused by an ATP decrease in hepatocytes in fructose medium resulting in a low energy charge (E.C.) (0.6) as compared to hepatocytes in glucose medium (0.9). Only menadione caused a decrease iin the E.C. in glucose medium while NQ caused a decrease of all three adenine nucleotides. In fructose medium, quinone-exposed hepatocytes showed no change in their adenine nucleotides as compared to control cells. Despite the higher oxidised glutathione content and the lower ATP level of NQ-exposed hepatocytes in fructose medium, they had a better viability than those cells in glucose medium. From our results we conclude that a high ATP content is not always beneficial for cell survival.

Marine Sesquiterpene Quinones and Hydroquinones: Acid-Catalyzed Rearrangements and Stereochemical Investigations

Acid treatment of both ilimaquinone (3) and 5-epi-ilimaquinone (9) yielded the same rearrangement products, (7) and (8), thus defining a common absolute stereochemistry. Likewise, acid- catalysed rearrangement of avarol (10) and arenarol (11) yielded the common product aureol (13), allowing the absolute stereochemistry of arenarol (11) and its related quinone arenarone (12) to be assigned. This latter acid- catalysed rearrangement also yielded an unexpected electrophilic aromatic cyclization product (15), the dimethyl ether (17) of which could be obtained in quantitative yield from acid treatment of avarol dimethyl ether (16).

Cytotoxicity of menadione and related quinones in freshly isolated rat hepatocytes: effects on thiol homeostasis and energy charge.

The cytotoxic events in freshly isolated rat hepatocytes following exposure over 2 h to menadione (2-methyl-1,4-naphthoquinone) and two closely related quinones, 2,3-dimethyl-1,4-naphthoquinone (DMNQ) and 1,4-naphthoquinone (NQ), were examined. These quinones differ in their arylation capacity (NQ > menadione >> DMNQ) and in their potential to induce redox cycling (NQ approximately menadione >> DMNQ) The glutathione status (reduced and oxidized glutathione) of the hepatocytes was determined using HPLC after derivatization with monobromobimane. Protein thiols were measured spectrophotometrically and the energy charge of the cells was determined with HPLC using ion pair chromatography. The leakage of lactate dehydrogenase was used as a marker for cell viability. All three quinones caused alterations of the glutathione status of the exposed cells but the effects were markedly different. Exposure to DMNQ resulted in a slow decrease of reduced glutathione and an increase of mixed disulfides. The other two quinones caused an almost complete depletion of reduced glutathione within 5 min. Hepatocytes exposed to NQ accumulated oxidized glutathione whereas menadione-exposed hepatocytes showed increased levels of mixed disulfides. We did not find any effects of DMNQ (200 microM) on protein thiols, energy charge or cell viability. There was a clear difference in the effects of menadione and NQ on protein thiols, energy charge and cell viability; exposure to NQ resulted in a more extensive decrease of protein thiols and energy charge and an earlier onset of lactate dehydrogenase leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanistic studies on tyrosinase-catalysed oxidative decarboxylation of 3,4-dihydroxymandelic acid

Mushroom tyrosinase, which is known to convert a variety of o-diphenols into o-benzoquinones, has been shown to catalyse an unusual oxidative decarboxylation of 3,4-dihydroxymandelic acid to 3,4-dihydroxybenzaldehyde [Sugumaran (1986) Biochemistry 25, 4489-4492]. The mechanism of this reaction was re-investigated. Although visible-region spectral studies of the reaction mixture containing 3,4-dihydroxymandelic acid and tyrosinase failed to generate the spectrum of a quinone product during the steady state of the reaction, both trapping experiments and non-steady-state kinetic experiments provided evidence for the transient formation of unstable 3,4-mandeloquinone in the reaction mixture. The visible-region spectrum of mandeloquinone resembled related quinones and exhibited an absorbance maximum at 394 nm. Since attempts to trap the second intermediate, namely alpha,2-dihydroxy-p-quinone methide, were in vain, mechanistic studies were undertaken to provide evidence for its participation. The decarboxylative quinone methide formation from 3,4-mandeloquinone dictates the retention of a proton on the alpha-carbon atom. Hence, if we replace this proton with deuterium, the resultant 3,4-dihydroxybenzaldehyde should retain the deuterium present in the original substrate. To test this hypothesis, we chemoenzymically synthesized alpha-deuterated 3,4-dihydroxymandelic acid and examined its enzymic oxidation. Our studies reveal that the resultant 3,4-dihydroxybenzaldehyde retained nearly 90% of the deuterium, strongly indicating the transient formation of quinone methide. On the basis of these findings it is concluded that the enzymic oxidation of 3,4-dihydroxymandelic acid generates the conventional quinone product, which, owing to its unstability, is rapidly decarboxylated to generate transient alpha,2-dihydroxy-p-quinone methide. The coupled dienone-phenol re-arrangement and keto-enol tautomerism of this quinone methide produce the observed 3,4-dihydroxybenzaldehyde.

Synthesis, peroxidating ability, and antineoplastic evaluation of 1-[(aminoalkyl)amino]-4-hydroxy-10-imino-9-anthracenones

A novel group of cytotoxic anthraquinone derivatives, 1-[(aminoalkyl)amino]-4-hydroxy-10-imino-9-anthracenones, has been synthesized. It has been shown that imino analogues of the anthracenediones exhibit diminished ability to generate oxygen radicals. The cytotoxic activity of iminoanthracenones obtained was lower than that of the related quinone carbonyl analogues. One of the obtained imino compounds showed a moderate antileukemic activity in vivo.

Epidermal ornithine decarboxylase induction and mouse skin tumor promotion by quinones

The generation of reactive oxygen species and the subsequent development of a pro-oxidant state, such as occurs during the redox cycling of quinones, has been suggested to play a role in the tumor promotion. Moreover, we have recently shown that the relative tumor promoting activity of a series of structurally related anthrones correlated with their ability to undergo base-catalyzed oxidation. We therefore analyzed dose-response relationships for skin tumor promoting activity and the ability to induce epidermal ornithine decarboxylase (ODC) with a series of structurally related quinones. 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. These two quinones also promoted papilloma formation in female SENCAR mice initiated with 25 nmol 7,12-dimethylbenz[a]anthracene at doses capable of inducing epidermal ODC. The tumor promoting response with juglone (1760 nmol) was dependent upon the frequency of application, with the highest tumor response obtained with a three times per week application regimen. In contrast, neither 1,8-dihydroxy-9,10-anthraquinone nor 1,4-benzoquinone, at doses up to 1760 nmol/mouse, had any effect on epidermal ODC, nor did they possess tumor promoting activity after 31 weeks of promotion. Interestingly, 3-methyl-1,4-naphthoquinone (meadione), a relatively good redox cycling quinone, at a dose of 3520 nmol had only very weak ODC inducing activity and after 31 weeks of promotion (1760 nmol) did not produce a significant papilloma response in SENCAR mice. Thus, there was a good correlation between the ability of structurally related quinones to induce epidermal ODC and their ability to behave as tumor promoters. In contrast, a relationship between quinone redox cycling and tumor promotion was not readily apparent. Finally, under optimal promoting conditions, juglone was very effective at supporting the conversion of papillomas to carcinomas (carcinoma/papilloma ratio of 0.35). In addition, histological examination of all tumors produced during promotion with juglone revealed the presence of both kerathoacanthomas and sebaceous squamous cell carcinomas. These latter tumors, not found in the anthrone group, may be indicative of a potentially unique site and/or mechanism of action for this class of compounds.

Chemical ecology of the luna moth

The effects of food plant on larval performance and midgut detoxification enzymes were investigated in larvae of the luna moth,Actias luna. Neonate larvae were fed leaves of black cherry, cottonwood, quaking aspen, white willow, red oak, white oak, tulip tree, paper birch, black walnut, butternut, or shagbark hickory. First instar survival, larval duration, and pupal weights were monitored as indices of food quality. Midgut enzyme preparations from fifth instars were assayed for β-glucosidase, quinone reductase, polysubstrate monooxygenase, esterase, and glutathione transferase activities. Larval survival on seven of the 11 plant species, including several recorded host plants, was extremely poor. Larvae performed well, and quite similarly, on birch, walnut, butternut, and hickory. Activities of all enzyme systems except β-glucosidase were significantly influenced by larval host plant. Of the systems assayed, quinone reductase and glutathione transferase activities were especially high. Comparisons of these values with published values for other Lepidoptera support the hypothesis that these enzyme systems are involved in conferring tolerance to juglone and related quinones occurring in members of the plant family Juglandaceae. Results suggest that host plant utilization by luna is more specialized at the individual or population level than at the species level and that biochemical detoxification systems may play a role in such specialization.

Irreversible inhibition of rat hepatic glutathione S-transferase isoenzymes by a series of structurally related quinones

The effect of several structurally related 1,4-benzoquinones (BQ) and 1,4-naphthoquinones (NQ) on the activity of rat hepatic glutathione S-transferases (GST) was studied. For the 1,4-benzoquinones, the extent of inhibition increased with an increasing number of halogen substituents. Neither the type of halogen nor the position of chlorine-atoms was of major importance. Similarly, 2,3-dichloro-NQ demonstrated a considerably higher inhibitory activity than 5-hydroxy-NQ. 2-Methyl derivatives of NQ did not inhibit GST activity at all. The irreversible nature of the inhibition was shown both by the time-course of the inhibition as well as by the fact that removal of the inhibitor by ultrafiltration did not restore the enzymatic activity. Incubation of quinones and enzyme in the presence of the competitive inhibitor S-hexylglutathione, slowed the inhibition considerably, indicating an involvement of the active site. Isoenzyme 3-3 was found to be most sensitive towards the whole series of inhibitors, whereas the activity of isoenzyme 2-2 was least affected in all cases. The inhibition by quinones is probably mainly due to covalent modification of a specific cysteine residue in or near the active site. The differential sensitivities of individual isoenzymes indicates that this residue is more accessible and/or easier modified in isoenzyme 3-3 than in any of the other isoenzymes tested. The findings suggest that quinones form a class of compounds from which a selective in vivo inhibitor of the GST might be developed.

Hydroxide-initiated gas-phase chemistry of anthraquinone and related quinones

Hydroxide-initiated gas-phase chemistry of anthraquinone and related quinones

Vitamin K3 (menadione) and related quinones, like tumor-promoting phorbol esters, alter the affinity of epidermal growth factor for its membrane receptors.

The effects of vitamin K3, quinones, fat-soluble vitamins, and various naturally occurring and synthetic compounds on the binding of 125I-epidermal growth factor (EGF) to mink lung cells or murine 3T3 cells in culture were studied. Vitamin K3, but not other fat-soluble vitamins, markeldy inhibits the binding of 125I-labeled EGF to treated cells, but does not affect the binding of insulin, concanavalin A, alpha-2-macroglobulin, and murine leukemia virus glycoprotein, gp70, to their membrane receptors. The binding of multiplication stimulating activity to treated cells is also reduced to some extent. Vitamin K3 alters the affinity of the receptors for EGF without changing the total number of available receptors per cell. Vitamin K3 modulation of EGF-receptor interaction is a temperature- and time-dependent phenomenon. EGF-receptor interaction is also significantly modulated by 1,4-naphthoquinone, 1,4-benzoquinone, and phenanthrenequinone but not by other quinones of anthracyclic antibiotics.

Ebenaceae extractives. Part 8. The structure of diosquinone and reactions of related quinone epoxides

Diosquinone, from Diospyros tricolor, is shown to be the naphthoquinonylnaphthoquinone epoxide (2). Juglone epoxides react with chloroform and with ethanol with the formation of chloro- and chlorohydroxy-juglones and of ethoxy- and ethoxyhydroxy-juglones respectively.

The ground state fundamentals of p-benzoquinone and p-benzoquinone- d4

The solid state infrared and Raman spectra of p-benzoquinone and several isotopic derivatives are reported and compared with the results of previous solution and vapor phase studies and with the results of previously published normal coordinate analyses. The vibrational assignments are discussed in terms of the vibronic activity observed in the phosphorescence spectra of the individual isotopically related quinones in several host lattices at 2°K. The infrared and Raman inactive fundamentals of p-benzoquinone- h 4 obtained from vibronic analyses of the vapor phase resonance fluorescence are reported. The six Raman active lattice modes of p-benzoquinone- h 4 and - d 4 are assigned with the aid of isotope shifts and thermal-anisotropic-motion amplitudes from previously published X-ray diffraction data.

Origin of the paramagnetic species in lignin solutions. Autoreduction of 2,6-dimethoxybenzoquinone and related quinones to radical anions in alkaline solution

Origin of the paramagnetic species in lignin solutions. Autoreduction of 2,6-dimethoxybenzoquinone and related quinones to radical anions in alkaline solution

Spectroscopic and structural studies of some oxocarbon condensation products: VI. The electronic structures of some hydroxyphenazines and quinones

Pariser-Parr-Pople molecular orbital calculations, including some configuration interaction, are reported for some hydroxyphenazines and related quinones. In general there is satisfactory agreement between the calculated charge density, bond order, electronic transition energy and oscillator strength values when compared with the available experimental data.

Spectroscopic and structural studies of some oxocarbon condensation products: VII. The electronic structures of some substituted hydroxyphenazines and quinones

The choice of suitable parameters for Pariser-Parr-Pople mo calculations on molecules containing the chloro, methyl, carboxyl and nitro groups is discussed. mo calculations including some configuration interaction are reported together with the electronic spectra of some substituted hydroxyphenazines and related quinones. The calculated and experimental transition energies and oscillator strengths are compared and reasonable agreement between them is found.

Cross-sensitization between synthetic primin and related quinones.

No abstract available