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Biochimica Et Biophysica Acta.... Aug 2022Quinones play important roles in biological electron transfer reactions in almost all organisms, with specific roles in many physiological processes and chemotherapy....
Quinones play important roles in biological electron transfer reactions in almost all organisms, with specific roles in many physiological processes and chemotherapy. Quinones participate in two-electron, two-proton reactions in aqueous solution at equilibrium near neutral pH, but protons often lag behind the electron transfers. The relevant reactions in proteins are often sequential one electron redox processes without involving protons. Here we report the aprotic electrochemistry of the two half-couples, Q/Q and Q/Q, of 11 parent quinones and 118 substituted 1,4-benzoquinones, 91 1,4-naphthoquinones, and 107 9,10-anthraquinones. The measured redox potentials are fit quite well with the Hammett para sigma (σ) parameter. Occasional exceptions can involve important groups, such as methoxy substituents in ubiquinone and hydroxy substituents in therapeutics. These can generally be explained by reasonable conjectures involving steric clashes and internal hydrogen bonds. We also provide data for 25 other quinones, 2 double quinones and 15 non-quinones, all measured under similar conditions.
Topics: Electrochemistry; Electron Transport; Naphthoquinones; Protons; Quinones
PubMed: 35413248
DOI: 10.1016/j.bbabio.2022.148558 -
Biomolecules Jul 2021Neutral cannabinoids are oxidatively unstable and are converted into quinone derivatives by atmospheric- and/or chemical oxidative dearomatization. The study of... (Review)
Review
Neutral cannabinoids are oxidatively unstable and are converted into quinone derivatives by atmospheric- and/or chemical oxidative dearomatization. The study of cannabinoquinones has long been plagued by their lability toward additional oxidative degradation, but full substitution of the quinone ring, as well as the introduction of steric hindrance on the alkyl substituent, have provided sufficient stability for a systematic investigation of their bioactivity and for further clinical development. These studies culminated in the discovery of the aminocannabinoquinone VCE-004.8 (), a compound under phase 2 clinical development with orphan drug status by EMA and FDA for the management of scleroderma. The synthesis and rich chemistry of these compounds will be described, summarizing their biological profile and clinical potential.
Topics: Cannabinoids; Humans; Oxidation-Reduction; Quinones
PubMed: 34356614
DOI: 10.3390/biom11070991 -
Food and Chemical Toxicology : An... Oct 2018The formation of o-quinones from direct 2-electron oxidation of catechols and/or two successive one electron oxidations could explain the cytotoxic/genotoxic and/or... (Review)
Review
The formation of o-quinones from direct 2-electron oxidation of catechols and/or two successive one electron oxidations could explain the cytotoxic/genotoxic and/or chemopreventive effects of several phenolic botanical extracts. For example, poison ivy contains urushiol, an oily mixture, which is oxidized to various o-quinones likely resulting in skin toxicity through oxidative stress and alkylation mechanisms resulting in immune responses. Green tea contains catechins which are directly oxidized to o-quinones by various oxidative enzymes. Alternatively, phenolic botanicals could be o-hydroxylated by P450 to form catechols in vivo which are oxidized to o-quinones. Examples include, resveratrol which is oxidized to piceatannol and further oxidized to the o-quinone. Finally, botanical o-quinones can be formed by O-dealkylation of O-alkoxy groups or methylenedioxy rings resulting in catechols which are further oxidized to o-quinones. Examples include safrole, eugenol, podophyllotoxin and etoposide, as well as methysticin. Once formed these o-quinones have a variety of biological targets in vivo resulting in various biological effects ranging from chemoprevention -> no effect -> toxicity. This U-shaped biological effect curve has been described for a number of reactive intermediates including o-quinones. The current review summarizes the latest data on the formation and biological targets of botanical o-quinones.
Topics: Activation, Metabolic; Alkylation; DNA; Glutathione; Hydroxylation; Oxidation-Reduction; Plants; Proteins; Quinones
PubMed: 30063944
DOI: 10.1016/j.fct.2018.07.050 -
Biomolecules Jul 2022Fungal quinones can be used for a variety of applications, such as pharmaceuticals, food colorants, textile dyes, and battery electrolytes. However, when producing...
Fungal quinones can be used for a variety of applications, such as pharmaceuticals, food colorants, textile dyes, and battery electrolytes. However, when producing quinones by fungal cultivation, many considerations arise regarding the feasibility of a production system, such as the quinone yield, purity, ease of extraction, and the co-production of mycotoxins. In this work, we display the initial screening of filamentous fungi for quinone production and evaluate their potential for future optimization. We investigated toluquinone (TQ) potentially produced by cf. , terreic acid (TA) produced by and , and anthraquinone (AQ) monomers and dimers produced by . The strains grew on various agar and/or liquid media and were analyzed by ultra-high-performance liquid chromatography-diode array detection-quadrupole time-of-flight mass spectrometry (UHPLC-DAD-QTOF MS). In the case of AQs, feature-based molecular networking (FBMN) was used for the identification of AQ analogs. TQ was not observed in the production strains. TA constituted one of the major chromatogram peaks and was secreted into the growth medium by . The AQs constituted many major chromatogram peaks in the mycelium extracts and endocrocin and citreorosein were observed extracellularly in small amounts.
Topics: Chromatography, High Pressure Liquid; Mass Spectrometry; Mycotoxins; Penicillium; Quinones
PubMed: 36008938
DOI: 10.3390/biom12081041 -
British Journal of Pharmacology Jul 2017Azoreductases are flavoenzymes that have been characterized in a range of prokaryotes and eukaryotes. Bacterial azoreductases are associated with the activation of two... (Review)
Review
UNLABELLED
Azoreductases are flavoenzymes that have been characterized in a range of prokaryotes and eukaryotes. Bacterial azoreductases are associated with the activation of two classes of drug, azo drugs for the treatment of inflammatory bowel disease and nitrofuran antibiotics. The mechanism of reduction of azo compounds is presented; it requires tautomerisation of the azo compound to a quinoneimine and provides a unifying mechanism for the reduction of azo and quinone substrates by azoreductases. The importance of further work in the characterization of azoreductases from enteric bacteria is highlighted to aid in the development of novel drugs for the treatment of colon related disorders. Human azoreductases are known to play a crucial role in the metabolism of a number of quinone-containing cancer chemotherapeutic drugs. The mechanism of hydride transfer to quinones, which is shared not only between eukaryotic and prokaryotic azoreductases but also the wider family of NAD(P)H quinone oxidoreductases, is outlined. The importance of common single nucleotide polymorphisms (SNPs) in human azoreductases is described not only in cancer prognosis but also with regard to their effects on the efficacy of quinone drug-based cancer chemotherapeutic regimens. This highlights the need to screen patients for azoreductase SNPs ahead of treatment with these regimens.
LINKED ARTICLES
This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Azo Compounds; Bacteria; Humans; NADH, NADPH Oxidoreductases; Neoplasms; Nitrofurans; Nitroreductases; Quinones
PubMed: 27487252
DOI: 10.1111/bph.13571 -
Marine Drugs Feb 2012The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development... (Review)
Review
The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development of new drugs. A review dealing with different strategies for obtaining bioactive terpenyl quinones/hydroquinones is presented. The different synthetic approches for the preparation of the most relevant quinones/hydroquinones are described.
Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Chemistry, Pharmaceutical; Humans; Hydroquinones; Quinones; Terpenes
PubMed: 22412807
DOI: 10.3390/md10020358 -
Molecules (Basel, Switzerland) Jul 2023This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in... (Review)
Review
This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition patterns across the 60-cell line panel of the NCI Developmental Therapeutics Program (DTP). Many natural products and synthetic analogues are revealed as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates, through correlations to dipyridoimidazo[5,4-]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of the active compound with benzo[]perimidines, phenoxazinones, benz[]pyrido[1,2-]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-]naphthoquinones, hypothesised as prodrugs. Compounds with very strong correlations to known TrxR inhibitors had inverse correlations to the expression of both reductase enzymes, NQO1 and TrxR, including naphtho[2,3-][1,4]oxazepane-6,11-diones, benzo[]carbazole-1,4-diones, pyranonaphthoquinones (including kalafungin, nanaomycin A, and analogues of griseusin A), and discorhabdin C. Quinoline-5,8-dione scaffolds based on streptonigrin and lavendamycin can correlate to either reductase. Inhibitors of TrxR are not necessarily (imino)quinones, e.g., parthenolides, while oxidising moieties are essential for correlations to NQO1, as with the mitosenes. Herein, an overview of synthetic methods and biological activity of each family of heterocyclic imino(quinone) is provided.
Topics: United States; National Cancer Institute (U.S.); Quinones; Indolequinones; Oxidoreductases; NAD(P)H Dehydrogenase (Quinone); Antineoplastic Agents; Neoplasms
PubMed: 37446864
DOI: 10.3390/molecules28135202 -
Molecules (Basel, Switzerland) Sep 2022Vitamin E, a collection of lipophilic phenolic compounds based on chroman-6-ol, has a rich and fascinating oxidative chemistry involving a range of intermediate forms,... (Review)
Review
Vitamin E, a collection of lipophilic phenolic compounds based on chroman-6-ol, has a rich and fascinating oxidative chemistry involving a range of intermediate forms, some of which are proposed to be important in its biological functions. In this review, the available electrochemical and spectroscopic data on these oxidized intermediates are summarized, along with a discussion on how their lifetimes and chemical stability are either typical of similar phenolic and chroman-6-ol derived compounds, or atypical and unique to the specific oxidized isomeric form of vitamin E. The overall electrochemical oxidation mechanism for vitamin E can be summarized as involving the loss of two-electrons and one-proton, although the electron transfer and chemical steps can be controlled to progress along different pathways to prolong the lifetimes of discreet intermediates by modifying the experimental conditions (applied electrochemical potential, aqueous or non-aqueous solvent, and pH). Depending on the environment, the electrochemical reactions can involve single electron transfer (SET), proton-coupled electron transfer (PCET), as well as homogeneous disproportionation and comproportionation steps. The intermediate species produced via chemical or electrochemical oxidation include phenolates, phenol cation radicals, phenoxyl neutral radicals, dications, diamagnetic cations (phenoxeniums) and -quinone methides. The cation radicals of all the tocopherols are atypically long-lived compared to the cation radicals of other phenols, due to their relatively weak acidity. The diamagnetic cation derived from α-tocopherol is exceptionally long-lived compared to the diamagnetic cations from the other β-, γ- and δ-isomers of vitamin E and compared with other phenoxenium cations derived from phenolic compounds. In contrast, the lifetime of the phenoxyl radical derived from α-tocopherol, which is considered to be critical in biological reactions, is typical for what is expected for a compound with its structural features. Over longer times via hydrolysis reactions, hydroxy -quinone hemiketals and quinones can be formed from the oxidized intermediates, which can themselves undergo reduction processes to form intermediate anion radicals and dianions. Methods for generating the oxidized intermediates by chemical, photochemical and electrochemical methods are discussed, along with a summary of how the final products vary depending on the method used for oxidation. Since the intermediates mainly only survive in solution, they are most often monitored using UV-vis spectroscopy, FTIR or Raman spectroscopies, and EPR spectroscopy, with the spectroscopic techniques sometimes combined with fast photoinitiated excitation and time-resolved spectroscopy for detection of short-lived species.
Topics: Benzoquinones; Chromans; Electron Spin Resonance Spectroscopy; Oxidation-Reduction; Phenol; Phenols; Protons; Solvents; Tocopherols; Vitamin E; alpha-Tocopherol
PubMed: 36234726
DOI: 10.3390/molecules27196194 -
Proceedings of the National Academy of... Mar 2023Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the...
Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the "orphan" two-component response regulator protein MSMEG_2064 as a subunit of the assembly. MSMEG_2064 in the complex occupies a site similar to the proposed redox-sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel, comparable to ubiquinone in other structures and suggesting a conserved quinone binding mechanism.
Topics: Electron Transport Complex I; Ubiquinone; Vitamin K 2; Quinones; Mycobacterium smegmatis
PubMed: 36952383
DOI: 10.1073/pnas.2214949120 -
Marine Drugs Nov 2010The 1,4-benzoquinone moiety is a common structural feature in a large number of compounds that have received considerable attention owing to their broad spectrum of... (Review)
Review
The 1,4-benzoquinone moiety is a common structural feature in a large number of compounds that have received considerable attention owing to their broad spectrum of biological activities. The cytotoxic and antiproliferative properties of many natural sesquiterpene quinones and hydroquinones from sponges of the order Dictyoceratida, such as avarol, avarone, illimaquinone, nakijiquinone and bolinaquinone, offer promising opportunities for the development of new antitumor agents. The present review summarizes the structure and cytotoxicity of natural terpenequinones/hydroquinones and their bioactive analogues and derivatives.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Hydroquinones; Molecular Structure; Porifera; Quinones; Structure-Activity Relationship; Terpenes
PubMed: 21339953
DOI: 10.3390/md8122849