naphthoquinones and dichlone

Molecular hybridization has proven to be a successful multi-target strategy in the design and development of new antitumor agents. Based on this rational approach, we have planned hybrid molecules containing covalently linked pharmacophoric units, present individually in compounds acting as inhibitors of the cancer protein targets tubulin, human topoisomerase II and ROCK1. Seven new molecules, selected by docking calculation of the complexes with each of the proteins taken into consideration, have been efficiently synthesized starting from 2,3-dichloro-1,4-naphtoquinone or 6,7-dichloro-5,8-quinolinquinone. By screening the full National Cancer Institute (NCI) panel, including 60 human cancer cell lines, four molecules displayed good and sometimes better growth inhibition GI

Topics: Amides; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; DNA Topoisomerases, Type II; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Docking Simulation; Molecular Structure; Naphthoquinones; Neoplasms; Podophyllotoxin; Pyridines; Quinolines; rho-Associated Kinases; Stilbenes; Structure-Activity Relationship; Topoisomerase II Inhibitors; Tubulin; Tubulin Modulators

This work presents the development, validation and application of four simple and direct spectrophotometric methods for determination of sodium valproate (VP) through charge transfer complexation reactions. The first method is based on the reaction of the drug with p-chloranilic acid (p-CA) in acetone to give a purple colored product with maximum absorbance at 524nm. The second method depends on the reaction of VP with dichlone (DC) in dimethylformamide forming a reddish orange product measured at 490nm. The third method is based upon the interaction of VP and picric acid (PA) in chloroform resulting in the formation of a yellow complex measured at 415nm. The fourth method involves the formation of a yellow complex peaking at 361nm upon the reaction of the drug with iodine in chloroform. Experimental conditions affecting the color development were studied and optimized. Stoichiometry of the reactions was determined. The proposed spectrophotometric procedures were effectively validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curves of the formed color products with p-CA, DC, PA and iodine showed good linear relationships over the concentration ranges 24-144, 40-200, 2-20 and 1-8μg/mL respectively. The proposed methods were successfully applied to the assay of sodium valproate in tablets and oral solution dosage forms with good accuracy and precision. Assay results were statistically compared to a reference pharmacopoeial HPLC method where no significant differences were observed between the proposed methods and reference method.

Topics: Anticonvulsants; Benzoquinones; Dosage Forms; Indicators and Reagents; Naphthoquinones; Spectrophotometry; Valproic Acid

Electron transfer processes in cyanobacterial photosystem I particles from Synechocystis sp. PCC 6803 with a high potential naphthoquinone (2,3-dichloro-1,4-naphthoquinone) incorporated into the A1 binding site have been studied at 298 and 77K using time-resolved visible and infrared difference spectroscopy. The high potential naphthoquinone inhibits electron transfer past A1, and biphasic P700(+)A1(-) radical pair recombination is observed. The two phases are assigned to P700(+)A1B(-) and P700(+)A1A(-) recombination. Analyses of the transient absorption changes indicate that the ratio of A- and B-branch electron transfer is 95:5 at 77 K and 77:23 at 298 K.

Topics: Bacterial Proteins; Chlorophyll; Electron Transport; Mutation; Naphthoquinones; Photosystem I Protein Complex; Spectrophotometry; Synechocystis; Temperature; Time Factors; Vitamin K 1

Photosystem I (PS I) has two nearly identical branches of electron-transfer co-factors. Based on point mutation studies, there is general agreement that both branches are active at ambient temperature but that the majority of electron-transfer events occur in the A-branch. At low temperature, reversible electron transfer between P(700) and A(1A) occurs in the A-branch. However, it has been postulated that irreversible electron transfer from P(700) through A(1B) to the terminal iron-sulfur clusters F(A) and F(B) occurs via the B-branch. Thus, to study the directionality of electron transfer at low temperature, electron transfer to the iron-sulfur clusters must be blocked. Because the geometries of the donor-acceptor radical pairs formed by electron transfer in the A- and B-branch differ, they have different spin-polarized EPR spectra and echo-modulation decay curves. Hence, time-resolved, multiple-frequency EPR spectroscopy, both in the direct-detection and pulse mode, can be used to probe the use of the two branches if electron transfer to the iron-sulfur clusters is blocked. Here, we use the PS I variant from the menB deletion mutant strain of Synechocyctis sp. PCC 6803, which is unable to synthesize phylloquinone, to incorporate 2,3-dichloro-1,4-naphthoquinone (Cl(2)NQ) into the A(1A) and A(1B) binding sites. The reduction midpoint potential of Cl(2)NQ is approximately 400 mV more positive than that of phylloquinone and is unable to transfer electrons to the iron-sulfur clusters. In contrast to previous studies, in which the iron-sulfur clusters were chemically reduced and/or point mutations were used to prevent electron transfer past the quinones, we find no evidence for radical-pair formation in the B-branch. The implications of this result for the directionality of electron transfer in PS I are discussed.

Topics: Binding Sites; Cold Temperature; Electron Spin Resonance Spectroscopy; Electron Transport; Iron-Sulfur Proteins; Kinetics; Mutation; Naphthoquinones; Photosystem I Protein Complex; Quinones; Temperature

Various spectroscopy techniques (UV-Vis, DRS, FT-IR, (1)H NMR, LC-MS) and theoretical computations have been employed to investigate the mechanism of the nucleophilic substitution reaction of 2,3-dichloronaphthoquinone (DCNQ) with para-substituted anilines in solid state under base- and solvent-free conditions against traditional synthetic routes. The initial formations of electron donor acceptor (EDA) adduct between DCNQ and aniline was found to be the driving force for the substitution reaction to occur in solid phase.

Topics: Aniline Compounds; Computer Simulation; Electrons; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Chemical; Models, Molecular; Naphthoquinones; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

Legislation at state, federal, and international levels is requiring rapid evaluation of the toxicity of numerous chemicals. Whole-animal toxicologic studies cannot yield the necessary throughput in a cost-effective fashion, leading to a critical need for a faster and more cost-effective toxicologic evaluation of xenobiotics.. We tested whether mechanistically based screening assays can rapidly provide information on the potential for compounds to affect key enzymes and receptor targets, thus identifying those compounds requiring further in-depth analysis.. A library of 176 synthetic chemicals was prepared and examined in a high-throughput screening (HTS) manner using nine enzyme-based and five receptor-based bioassays.. All the assays have high Z' values, indicating good discrimination among compounds in a reliable fashion, and thus are suitable for HTS assays. On average, three positive hits were obtained per assay. Although we identified compounds that were previously shown to inhibit a particular enzyme class or receptor, we surprisingly discovered that triclosan, a microbiocide present in personal care products, inhibits carboxylesterases and that dichlone, a fungicide, strongly inhibits the ryanodine receptors.. Considering the need to rapidly screen tens of thousands of anthropogenic compounds, our study shows the feasibility of using combined HTS assays as a novel approach toward obtaining toxicologic data on numerous biological end points. The HTS assay approach is very useful to quickly identify potentially hazardous compounds and to prioritize them for further in-depth studies.

Topics: Animals; Carboxylesterase; High-Throughput Screening Assays; Humans; Naphthoquinones; Receptors, Androgen; Receptors, Aryl Hydrocarbon; Receptors, Estrogen; Ryanodine Receptor Calcium Release Channel; Toxicology; Triclosan

4-Acetamidophenol (paracetamol) is shown to form charge transfer complex with 2,3-dichloro1,4-naphthoquinone in aqueous ethanol media exhibiting the unusual 2:1 (paracetamol:quinone) stoichiometry. The complexation enthalpy and entropy have been estimated from the formation constant (K) determined spectrophotometrically at five different temperatures. In aqueous ethanol mixtures of varying composition K increases with increasing dielectric constant of the medium. This has been rationalized by calculating the electronic charge distribution in paracetamol molecule and its conjugate base at the DFT/B3LYP/6-31++G(d,p) level. The theoretically calculated vertical ionization potential of paracetamol also agrees with reported experimental value.

Topics: Acetaminophen; Electrochemistry; Ethanol; Molecular Structure; Naphthoquinones; Solutions; Spectrophotometry; Spectrophotometry, Ultraviolet; Thermodynamics; Water

The rapid interaction between 2,3-dichloro-1,4-naphthoquinone (DClNQ) and n-butylamine results in the formation of 2N(n-butylamino)-3-chloro-1,4-naphthoquinone as the final product. The reaction is found to proceed through the initial formation of charge-transfer (CT) complex as an intermediate. The final product of the reaction has been isolated and characterized using FTIR, H1 and C13 NMR spectroscopy, mass spectrometry, and elemental analysis. The rate of formation of product has been measured as a function of time in different halocarbon solvents, viz., chloroform, dichloromethane and 1:1 (v/v) mixture of two solvents. The pseudo first order and second order rate constants at various temperatures for the transformation process were evaluated from the absorbance time data. The activation parameters (E(a), DeltaS#, DeltaH#, and DeltaG#) were obtained from temperature dependence of rate constants. The influence of dielectric constant on the properties of reaction was discussed and the probable course of reaction is presented.

Topics: Butylamines; Carbon; Chloroform; Electrochemistry; Kinetics; Magnetic Resonance Spectroscopy; Mass Spectrometry; Methylene Chloride; Models, Chemical; Naphthoquinones; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Temperature; Thermodynamics; Ultraviolet Rays

The reaction between 2,3-dichloro-1,4-naphthoquinone and N,N'-diphenyl thiourea in acetonitrile medium, which yields the product, 2,3-(N,N'-diphenylthioureylene)-naphtho-1,4-quinone has been found to take place in two ways--thermal and photochemical. The thermal (dark) reaction occurs through an electron donor-acceptor (EDA) adduct as intermediate with evolution of HCl and kinetic data fit into the scheme A + B<==>AB(fast)-->product(slow) Formation constant of the EDA adduct and the rate constant of the slow process have been determined at four different temperatures from which the enthalpy of formation of AB has been determined. The photochemical reaction has been studied with 360 nm ordinary light and also with 365 and 370 nm laser beams. Use of laser causes about 10(3)-fold increase in the rate of the reaction but does not affect the quantum yield. The final product has been isolated and characterised by elemental analysis, 1H and 13C NMR, IR spectroscopy and mass spectrometry.

Topics: Electron Transport; Kinetics; Magnetic Resonance Spectroscopy; Naphthoquinones; Photochemistry; Spectrophotometry; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Thiourea

Isopropyl-alkylamines 2 react with 2,3-dichloro-1,4-naphthoquinone (1) to give red 2-chloro-3-isopropyl-alkylamino-1,4-naphthoquinones 3 and with 2,3-dichloro-1,4-naphthoquinone/acetaldehyde to give blue 2-chloro-3-isopropylalkylamino-vinyl-1,4-naphthoquinones 7. It is evident that the formation of 7 is preferred sterically to the formation of 3. The reaction between 2, 1 and acetaldehyde give also red aminoquinones 3 and blue green 2-chloro-3-(4-isopropylalkylamino-buta-1,3-dienyl)-1,4-naphthoquinone like 11.

Topics: Acetaldehyde; Coloring Agents; Indicators and Reagents; Magnetic Resonance Spectroscopy; Molecular Conformation; Naphthoquinones; Propylamines; Spectrophotometry, Infrared

Dialkylamine drugs desipramine, propanolol, pindolol, alprenolol and metoprolol 4a-e react with 2,3-dichloro-1,4-naphthoquinone (2) and acetaldehyde to give red coloured 2-dialkylamino-3-chloro-1,4-naphthoquinones 5a, b, d, e, blue coloured 2-dialkylamino-vinyl-3-chloro-1,4-naphtho-quinones 1a-e and bluish green coloured 2-dialkylamino-butadienyl-3-chloro-1,4-naphthoquinones 6b-e. The colour products are isolated by column chromatography.

Topics: Acetaldehyde; Chromatography; Colorimetry; Indicators and Reagents; Magnetic Resonance Spectroscopy; Naphthoquinones; Pharmaceutical Preparations; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet

Topics: Amines; Indicators and Reagents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Naphthoquinones; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet

Chloranil and 2,3-dichloro-1,4-naphthoquinone have been linked to different natural and unnatural amino acids via a vinylic spacer. Two routes were developed for the facile preparation of these novel modified amino acids: the direct method, which can only be applied to secondary amines, and the indirect method (transamination reaction), which can be applied to any amino acid or ester.

Topics: Amino Acids; Benzoquinones; Chloranil; Indicators and Reagents; Magnetic Resonance Spectroscopy; Models, Chemical; Naphthoquinones

Southern armyworm, Spodoptera eridania, larvae were provided ad libitum 0.002-0.25% w/w dichlone, 2,3-dichloro-1,4-naphthoquinone (CNQ). Larval mortality occurred in a time-and-dose dependent manner, with an LC17 of 0.01% and an LC50 of 0.26% CNQ at day-5. Extracts of larvae fed control, 0.01, and 0.25% CNQ diets for 5 days were assayed for antioxidant enzymes. While 0.01% CNQ had a mild effect, 0.25% CNQ profoundly increased levels of all antioxidant enzymes that were examined. The increases as compared to control were: 5.3-, 1.9-, 3.2-, 2.6-, 2.8-, and 3.5-fold higher for superoxide dismutase, catalase, glutathione transferase and its peroxidase activity, glutathione reductase and DT-diaphorase, respectively. At 0.01% CNQ, the thiobarbituric acid reactive substances (TBARS) were similar to the control group. However, despite the induction from 0.25% CNQ of all enzymes examined, the lipid peroxidation was not attenuated; the TBARS were 29.7% over the control value. High mortalities and CNQ-induced pathologies reflected in retarded growth, wasting syndrome, and diuresis clearly indicated that the insect sustained severe oxidant-induced injuries before appropriate defenses were fully mobilized. Thus, this quinone causes an oxidative stress in a model insect species analogous to that observed in mammalian species.

Topics: Animals; Fungicides, Industrial; Larva; Lethal Dose 50; Naphthoquinones; Oxidative Stress; Oxidoreductases; Spodoptera

Several 1-alkoxy-2,3-dichloro-4-hydroxynaphthalene derivatives were prepared. These compounds were oxidized by hydrogen peroxide in the presence of a peroxidase to give 2,3-dichloro-1,4-naphthoquinone, which then reacted with various alkyl benzoylacetates to develop blue coloration with absorption maximum at greater than 600 nm. The color development reaction can be applied to the determination of appropriate serum constituents such as cholesterol.

Topics: Color; Hydrogen Peroxide; Magnetic Resonance Spectroscopy; Naphthols; Naphthoquinones; Solutions; Spectrophotometry, Infrared

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-hexyl-glutathione, 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.

Topics: Animals; Benzoquinones; Glutathione; Glutathione Transferase; Isoenzymes; Liver; Molecular Structure; Naphthoquinones; Quinones; Rats; Structure-Activity Relationship

Topics: Administration, Oral; Aniline Hydroxylase; Animals; Cytochrome P-450 Enzyme System; Female; Fungicides, Industrial; Injections, Subcutaneous; Liver; Male; Mitochondria, Liver; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Quinone Reductases; Rats; Rats, Inbred Strains

Dietary exposure of rats to a high concentration of 2,3-dichloro-1,4-naphthoquinone (CNQ) (2 g/kg diet) for 60 days altered cardiac mitochondrial function and activities of anti-oxidant enzymes in hepatic and cardiac tissue. CNQ moderately depressed the cardiac mitochondrial respiratory control ratio (RCR) to 85% of control; this was exacerbated to 60% of control in animals fed alpha-tocopherol-deficient diets. Dietary CNQ increased hepatic superoxide dismutase (SOD) and catalase activities and increased cardiac SOD activity, but depressed cardiac glutathione reductase and hepatic glutathione peroxidase activities. These effects are consistent with previous in vitro findings that CNQ induces oxidative stress. No significant differences in heart weight or body weight were observed in rats fed CNQ as compared to untreated controls.

Topics: Animals; Antioxidants; Body Weight; Catalase; Diet; Glutathione Peroxidase; Glutathione Reductase; Heart; Liver; Myocardium; Naphthoquinones; Organ Size; Oxygen Consumption; Rats; Superoxide Dismutase; Vitamin E Deficiency

Topics: Animals; Diet; Female; Free Radicals; Fungicides, Industrial; Glycolysis; Liver; Liver Glycogen; Naphthoquinones; Oxygen; Rats; Rats, Inbred Strains; Sulfhydryl Compounds

The addition of 2,3-dichloro-1,4-naphthoquinone (CNQ) to substrate-depleted, GSH-supplemented rat liver mitochondria resulted in a dose-dependent depletion of reactable suflhydryl groups and a concomitant increase in mitochondrial disulfide content at a ratio of 2 thiols depleted/disulfide generated. The molar ratio of thiol depleted/CNQ added approached 20 at low CNQ concentrations and was unity at higher doses. The addition of CNQ to substrate-depleted mitochondrial suspensions resulted in O2 consumption which increased with increasing concentrations of mitochondria and was sensitive to N-ethylmaleimide (NEM) which establishes the ability of CNQ to interact with mitochondrial thiol redox centers. The CNQ-mediated large amplitude swelling of rat liver mitochondria was exacerbated by thiol oxidizing agents and depressed by disulfide reducing agents. A redox cycling mechanism between mitochondrial thiol groups, CNQ and oxygen was proposed to lower the matrix glutathione pool and make the mitochondria more susceptable to toxic oxygen radicals which induce swelling in isolated mitochondrial suspensions. In support of this mechanism, alpha-tocopherol was shown to prevent the CNQ-mediated swelling process. Beef heart mitochondrial NADH was oxidized by CNQ in a 1/1 molar ratio anaerobically and in a 3/1 molar ratio under aerobic conditions, whereas the fully reduced quinone, CNQH2, oxidized NADH aerobically but not anaerobically. Thus, CNQ is capable of interacting with NADH of the mitochondrial electron transport chain in a redox cycling fashion.

Topics: Animals; Cattle; Disulfides; Herbicides; Intracellular Membranes; Kinetics; Mitochondria, Heart; Mitochondria, Liver; Mitochondrial Swelling; NAD; Naphthoquinones; Oxidation-Reduction; Oxygen Consumption; Rats; Sulfhydryl Compounds

The addition of 2,3-dichloro-1,4-naphthoquinone (CNQ) to isolated mitochondria supplemented with GSSG resulted in a respiratory burst with the production of O2- and H2O2, and a decrease in the level of measurable disulfide. Superoxide generated by the xanthine oxidase system or by CNQ-treated mitochondria caused the reduction of GSSG to GSH. Both disulfide reductions were partially sensitive to exogeneous SOD. GSSG was also shown to interfere with the epinephrine - adrenochrome superoxide assay system. The findings reported herein support the conclusion that GSSG is capable of scavenging O2- and has the potential to scavenge other free radicals by a similar mechanism.

Topics: Animals; Cattle; Epinephrine; Glutathione; Glutathione Disulfide; In Vitro Techniques; Mitochondria, Liver; Naphthoquinones; Rats; Superoxides

A sensitive method for spectrophotometric determination of methimazole is based on the reaction of this compound with 2,3-dichloro-1,4-naphtoquinone in presence of ammonia. The colour thus formed is stable, reproducible and linear in the range 0,4 to 4 micrograms/ml of methimazole concentration. This method has been employed successfully for estimation of the antithyroid drug in plasma sample with good recovery (75 +/- 2%). The colour is due to formation of a red compound of molecular formula C14H11O2N3S, deduced from elemental analysis and mass spectrum.

Topics: Ammonia; Drug Interactions; Humans; Methimazole; Naphthoquinones; Spectrophotometry

Topics: Animals; Cattle; Dose-Response Relationship, Drug; Hydrogen Peroxide; Intracellular Membranes; Mitochondria, Heart; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Naphthoquinones; Oxygen; Oxygen Consumption; Rats; Succinate Dehydrogenase; Superoxides; Time Factors

Topics: Face; Mouth; Naphthols; Naphthoquinones

Topics: Anti-Infective Agents; Antifibrinolytic Agents; Heparin Antagonists; Humans; Naphthoquinones; Retinoids; Vitamin K; Vitamins