chiniofon and quinone

Hybrids 1,4-quinone with quinoline were obtained by connecting two active structures through an oxygen atom. This strategy allows to obtain new compounds with a high biological activity and suitable bioavailability. Newly synthesized compounds were characterized by various spectroscopic methods. The enzymatic assay used showed that these compounds were a suitable DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. Hybrids were tested in vitro against a panel of human cell lines including melanoma, breast, and lung cancers. They showed also a high cytotoxic activity depending on the type of 1,4-quinone moiety and the applied tumor cell lines. It was found that cytotoxic activity of the studied hybrids was increasing against the cell lines with higher NQO1 protein level, such as breast (MCF-7 and T47D) and lung (A549) cancers. Selected hybrids were tested for the transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and the apoptosis pathway (BCL-2 and BAX). The molecular docking was used to examine the probable interaction between the hybrids and NQO1 protein.

Topics: Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Benzoquinones; Cell Line, Tumor; Drug Screening Assays, Antitumor; Histones; Humans; Hydroxyquinolines; Molecular Docking Simulation; NAD(P)H Dehydrogenase (Quinone); Oxygen; Quinolines; Quinones; Streptonigrin; Tumor Suppressor Protein p53

Gold electrode surface is modified via covalent attachment of a synthesized thiol functionalized with 8-hydroxyquinoline, p-((8-hydroxyquinoline)azo) benzenethiol (SHQ), for the first time. The behavior of the nanostructured electrode surface (Au-SHQ) is characterized by electrochemical techniques including cyclic and differential pulse voltammetry (CV and DPV), and electrochemical impedance spectroscopy (EIS). The modified surface is stable in a wide range of potentials and pHs. A surface pKa of 6.0±0.1 is obtained for Au-SHQ electrode using surface acid/base titration curves constructed by CV and EIS measurements as a function of pH. These results helped to determine the charge state of the surface as a function of pH. The gold modified electrode surface showed good affinity for sensing the Al(III) ion at pH 5.5. The sensing process is based on (i) accumulation and complex formation between Al(III) from the solution phase and 8HQ function on the Au electrode surface (recognition step) and (ii) monitoring the impedance of the Au-SHQ-Al(III) complex against redox reaction rate of parabenzoquinone (PBQ) (signal transduction step). The PBQ is found to be a more suitable probe for this purpose, after testing several others. Thus, the sensor was tested for quantitative determination of Al(III) from the solution phase. At the optimized conditions, a linear response, from 1.0×10(-11) to 1.2×10(-5) M Al(III) in semi-logarithmic scale, with a detection limit of 8.32×10(-12) M and mean relative standard deviation of 3.2% for n=3 at 1.0×10(-7) M Al(III) is obtained. Possible interferences from coexisting cations and anions are also studied. The results show that many ions do not interfere significantly with the sensor response for Al(III). Validity of the method and applicability of the sensor are successfully tested by determination of Al(III) in human blood serum samples.

Topics: Adsorption; Aluminum; Azo Compounds; Benzoquinones; Dielectric Spectroscopy; Electrochemistry; Electrodes; Gold; Humans; Hydrogen-Ion Concentration; Hydroxyquinolines; Oxidation-Reduction; Quinolines; Surface Properties

Melanins are pigmentary macromolecules found throughout the biosphere that, in the 1970s, were discovered to conduct electricity and display bistable switching. Since then, it has been widely believed that melanins are naturally occurring amorphous organic semiconductors. Here, we report electrical conductivity, muon spin relaxation, and electron paramagnetic resonance measurements of melanin as the environmental humidity is varied. We show that hydration of melanin shifts the comproportionation equilibrium so as to dope electrons and protons into the system. This equilibrium defines the relative proportions of hydroxyquinone, semiquinone, and quinone species in the macromolecule. As such, the mechanism explains why melanin at neutral pH only conducts when "wet" and suggests that both carriers play a role in the conductivity. Understanding that melanin is an electronic-ionic hybrid conductor rather than an amorphous organic semiconductor opens exciting possibilities for bioelectronic applications such as ion-to-electron transduction given its biocompatibility.

Topics: Benzoquinones; Electric Conductivity; Electron Spin Resonance Spectroscopy; Hydroxyquinolines; Ion Transport; Melanins; Mesons; Semiconductors; Water

Succinate:menaquinone oxidoreductase from Corynebacterium glutamicum, a high-G+C, Gram-positive bacterium, was purified to homogeneity. The enzyme contained two heme B molecules and three polypeptides with apparent molecular masses of 67, 29 and 23 kDa, which corresponded to SdhA (flavoprotein), SdhB (iron-sulfur protein), and SdhC (membrane anchor protein), respectively. In non-denaturating polyacrylamide gel electrophoresis, the enzyme migrated as a single band with an apparent molecular mass of 410 kDa, suggesting that it existed as a trimer. The succinate dehydrogenase activity assayed using 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone and 2,6-dichloroindophenol as the electron acceptor was inhibited by 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), and the Dixon plots were biphasic. In contrast, the succinate dehydrogenase activity assayed using phenazine methosulfate and 2,6-dichloroindophenol was inhibited by p-benzoquinone and not by HQNO. These findings suggested that the C. glutamicum succinate:menaquinone oxidoreductase had two quinone binding sites. In the phylogenetic tree of SdhA, Corynebacterium species do not belong to the high-G+C group, which includes Mycobacterium tuberculosis and Streptomyces coelicolor, but are rather close to the group of low-G+C, Gram-positive bacteria such as Bacillus subtilis. This situation may have arisen due to the horizontal gene transfer.

Topics: Benzoquinones; Corynebacterium glutamicum; Electron Transport Complex II; Heme; Hydroxyquinolines; Phylogeny

Cytochrome bc(1) is an integral membrane protein complex essential to cellular respiration and photosynthesis. The Q cycle reaction mechanism of bc(1) postulates a separated quinone reduction (Q(i)) and quinol oxidation (Q(o)) site. In a complete catalytic cycle, a quinone molecule at the Q(i) site receives two electrons from the b(H) heme and two protons from the negative side of the membrane; this process is specifically inhibited by antimycin A and NQNO. The structures of bovine mitochondrial bc(1) in the presence or absence of bound substrate ubiquinone and with either the bound antimycin A(1) or NQNO were determined and refined. A ubiquinone with its first two isoprenoid repeats and an antimycin A(1) were identified in the Q(i) pocket of the substrate and inhibitor bound structures, respectively; the NQNO, on the other hand, was identified in both Q(i) and Q(o) pockets in the inhibitor complex. The two inhibitors occupied different portions of the Q(i) pocket and competed with substrate for binding. In the Q(o) pocket, the NQNO behaves similarly to stigmatellin, inducing an iron-sulfur protein conformational arrest. Extensive binding interactions and conformational adjustments of residues lining the Q(i) pocket provide a structural basis for the high affinity binding of antimycin A and for phenotypes of inhibitor resistance. A two-water-mediated ubiquinone protonation mechanism is proposed involving three Q(i) site residues His(201), Lys(227), and Asp(228).

Topics: Amino Acid Sequence; Animals; Antimycin A; Benzoquinones; Cattle; Crystallography, X-Ray; Cytochrome b Group; Electron Transport Complex III; Enzyme Inhibitors; Hydroxyquinolines; Mitochondria, Heart; Models, Molecular; Molecular Sequence Data; Oxidation-Reduction; Protein Binding; Protein Conformation; Protein Subunits; Structure-Activity Relationship; Substrate Specificity; Ubiquinone

The light-harvesting chlorophyll a/b complex (LHC II) and four photosystem II (PS II) core proteins (8.3, 32, 34 and 44 kDa) become phosphorylated in response to reduction of the intersystem electron transport chain of green plant chloroplasts. Previous studies indicated that reduction of the plastoquinone (PQ) pool is the key event in kinase activation. However, we show here that, unlike PS II proteins, LHC II is phosphorylated only when the cytochrome b6f complex is active. Two lines of evidence support this conclusion. (1) 2,5-Dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB) and the 2,4-dinitrophenyl ether of iodonitrothymol (DNP-INT), which are known to block electron flow into the cytochrome complex, selectively inhibit LHC II phosphorylation in spinach thylakoids. (2) The hcf6 mutant of maize, which contains PQ but lacks the cytochrome b6f complex, phosphorylates the four PS II proteins but fails to phosphorylate LHC II in vivo or in vitro.

Topics: Benzoquinones; Chlorophyll; Chloroplasts; Cytochrome b Group; Cytochrome b6f Complex; Cytochromes; Cytochromes f; Dinitrobenzenes; Hydroxyquinolines; Mutation; Phosphoproteins; Phosphorylation; Photosynthesis; Plants; Quinones

The rate of NADH oxidation by inverted membrane vesicles prepared from the halotolerant bacterium Ba1 of the Dead Sea is increased specifically by sodium ions, as observed earlier in whole cells. The site of this sodium effect is identified as the NADH: quinone oxidoreductase, similarly to the other such system known, Vibrio alginolyticus (H. Tokuda and T. Unemoto (1984) J. Biol. Chem. 259, 7785-7790). Sodium accelerates quinone reduction severalfold, but oxidation of the quinol, with oxygen as terminal electron acceptor, is unaffected. The sodium-dependent pathway of quinone reduction exhibits higher apparent affinity to extraneous quinone (Q-2) than the sodium-insensitive pathway, and is specifically inhibited by 2-heptyl-4-hydroxyquinoline N-oxide. ESR spectra of the membranes contain a feature at g = 1.98 which is tentatively identified as one originating from semiquinone. This feature is increased by NADH and decreased by addition of Na+, suggesting that, as proposed from different kinds of evidence for the V. alginolyticus system, sodium affects the semiquinone reduction step. As in the other system, the site of sodium stimulation in Ba1 probably corresponds to the site of sodium translocation, which was shown earlier (S. Ken-Dror, R. Shnaiderman, and Y. Avi-Dor (1984) Arch. Biochem. Biophys. 229, 640-649) to be linked directly to a redox reaction in the respiratory chain.

Topics: Bacteria; Benzoquinones; Cytochrome b Group; Electron Transport; Hydrogen-Ion Concentration; Hydroxyquinolines; NAD; Oxidation-Reduction; Quinone Reductases; Quinones; Sodium; Succinates; Succinic Acid; Ubiquinone; Vibrio