Quinone Derivatives Research Articles

Suppression of Methane Generation during Methanogenesis by Chemically Modified Humic Compounds.

The introduction of various concentrations of chemically modified humic compounds (HC) with different redox characteristics into the media with free and immobilized anaerobic consortia accumulating landfill gases was studied as approach to their functioning management. For this purpose, quinone (hydroquinone, naphthoquinone or methylhydroquinone) derivatives of HC were synthesized, which made it possible to vary the redox and antioxidant properties of HC as terminal electron acceptors in methanogenic systems. The highest acceptor properties were obtained with potassium humate modified by naphthoquinone. To control possible negative effect of HC on the cells of natural methanogenic consortia, different bioluminescent analytical methods were used. The addition of HC derivatives, enriched with quinonones, to nutrient media at concentrations above 1 g/L decreased the energetic status of cells and the efficiency of the methanogenesis. For the first time, the significant decrease in accumulation of biogas was reached as effect of synthetic HC derivatives, whereas both notable change of biogas composition towards increase in the CO2 content and decrease in CH4 were revealed. Thus, modification with quinones makes it possible to obtain low-potential HC derivatives with strongly pronounced acceptor properties, promising for inhibition of biogas synthesis by methanogenic communities.

Theoretical and experimental findings regarding the electroanalysis of dienestrol in natural waters using a silver nanoparticles/single-walled carbon nanotubes-based amperometric sensor

Abstract Aware of the irreparable damage that synthetic estrogens can trigger in the environment, the search for analytical methods capable of mapping the sources, levels and fate of these micropollutants is a subject that demands enormous scientific effort. The present work follows this trend, reporting a silver nanoparticles/single-walled carbon nanotubes-based composite electrode (AgNP/SWCNT-CPE) that has multiple functionalities for dienestrol (DNL) electroanalysis. Theoretical and experimental data indicate that DNL reactivity on AgNP/SWCNT-CPE is more critical under acidic conditions, favoring its irreversible oxidation to quinone derivatives. The reaction kinetics is limited by interfacial adsorption events, whose intensity of the molecule-surface interaction depends on variables such as Gibbs free energy, ionization potential, HOMO-LUMO gap, and dipole moment. Since the silver‑carbon heterojunction has low overpotential towards the oxygen evolution reaction, it is speculated that AgNP/SWCNT-CPE is more resistant to surface fouling due to the formation of chemisorbed radicals on its electroactive area. Based on the detection limit (43.7 nmol L−1 DNL), the analytical performance of the proposed method is equivalent to those attained by chemiluminescence, electrophoresis, chromatography and electrochemistry. Given the sensitivity obtained, AgNP/SWCNT-CPE was successfully used to quantify DNL in river waters containing different levels of organic matter, without compromising the accuracy, stability and robustness of the amperometric measurements, reiterating the reliability and feasibility of this proposal.

Selenium content, antibacterial, antioxidant and anti-sickling activities of Zanthoxylum gilletii (De Wild) P.G. Waterman (Rutaceae)

Aim: The aim of this study was to identify bioactive compounds, to determine the mineral content and to evaluate the antibacterial, antioxidant and anti-sickling activities of different parts of Zanthoxylum gilletii.Methods: Phytochemical composition was evaluated by general tests as well as chromatographic technics (TLC and HPLC), the mineral micronutrient content was quantified by spectroscopy ICP-OES. The antioxidant activities of the infusions extracts from leaves, stem bark and root bark of Z. gilletii were evaluated using ABTS an DPPH assays, the antibacterial activity against four bacteria strains using the micro-dilution method; and the anti-sickling activity was assessed by the Emmel test.Results: Phytochemical screening revealed the presence of polyphenols such as anthocyanins and flavonoids (stem bark) while stem and root barks contained tannins. Alkaloids were found in the leaves, saponins in leaves, stem and root barks. Leaves and root bark also contained triterpenoids and steroids, while only stem bark contained quinonic derivatives. For phenolic acids and flavonoids, stem and root barks could contain luteolin, chlorogenic acid, caffeic acid and only stem bark could contain rutin. Mineral analysis revealed the presence of macronutrients and micronutrients including calcium, iron, zinc and selenium. All aqueous extracts displayed high ABTS and DPPH radical-scavenging activities at the concentration range of 1–25 ug/mL. The in vitro Emmel test showed that the aqueous extracts of the different parts had anti-sickling properties at the concentration of 10.42 µg/mL, 20.83 µg/mL, 83.30 µg/mL for the stem bark, the leaves and the root bark respectively. The stem bark was the most active extract. The results of antibacterial activity test indicated that the all extracts exhibited the highest activity against Staphyloccocus aureus, Escherichia coli, Enterococcus spp and Pseudomonas aeruginosa. Stem barks showed moderate activity against P. aeruginosa and root barks against S. aureus and Enterococcus spp respectively.Conclusions: The bioactivities of the different parts could be attributed to alkaloids, phenolic compounds and terpenes. Stem bark showed the best antioxidant, antibacterial and anti sickling activities. Z. gilletii contains the phytochemicals that validate its use in Traditional Medicine for the management of sickle cell disease.

Computational studies reveal mechanism by which quinone derivatives can inhibit SARS-CoV-2. Study of embelin and two therapeutic compounds of interest, methyl prednisolone and dexamethasone

BackgroundQuinones are reactive to proteins containing cysteine residues and the main protease in Covid-19 contains an active site that includes Cys145. Embelin, a quinone natural product, is known to have antiviral activity against influenza and hepatitis B. Preliminary studies by our group also indicate its ability to inhibit HSV-1 in cultured cells. MethodsDocking and DFT methods applied to the protease target. Resultsa mechanism for this inhibition of the SARS-CoV-2 Mpro protease is described, specifically due to formation of a covalent bond between S(Cys145) and an embelin C(carbonyl). This is assisted by two protein amino acids (1) N(imidazole-His41) which is able to capture H[S(Cys145)] and (2) HN(His163), which donates a proton to embelin O(carbonyl) forming an OH moiety that results in inhibition of the viral protease. A similar process is also seen with the anti-inflammatory drugs methyl prednisolone and dexamethasone, used for Covid-19 patients. Methyl prednisolone and dexamethasone are methide quinones, and possess only one carbonyl moiety, instead of two for embelin. Additional consideration was given to another natural product, emodin, recently patented against Covid-19, as well as some therapeutic quinones, vitamin K, suspected to be involved in Covid-19 action, and coenzyme Q10. All show structural similarities with embelin, dexamethasone and methyl prednisolone results. ConclusionsOur data on embelin and related quinones indicate that these natural compounds may represent a feasible, strategic tool against Covid-19.

Epoxyquinophomopsins A and B from endophytic fungus Phomopsis sp. and their activity against tyrosine kinase.

Two new quinone derivatives, epoxyquinophomopsins A (1) and B (2), were purified from the EtOAc extract of endophytic fungus Phomopsis sp isolated from Morus cathayana. The structures of both compounds were determined based on 1D and 2D NMR and mass spectral data, as well as by x-ray diffraction analysis for 1. Compounds 1 and 2 were screened against eight receptor- (RTKs) and eight non-receptor tyrosine kinases (nRTKs). Both compounds showed strong inhibitory properties against Bruton's Tyrosine Kinase (nRTK) with their kinase activity were 19% and 20%, respectively. Only compound 1 that showed strong inhibitory properties against RTKs EGFR and HER-4 with its kinase activity were 16 and 15%, respectively. Thus, both compounds have potential as tyrosine kinase inhibitors.

Nose to brain delivery of embelin with carbidopa nanoparticle for effective management of Parkisonism

Background: Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. Embelin reported for its antiparkinsonism effect by diverse mechanisms, namely by scavenging free radicals and antioxidant action. The entrance of embelin with carbidopa into the brain is limited and this work brings a new strategy to overcome these constrains by developing nanosystems capable of protecting embelin from the extensive degradation and metabolism and enhancing the delivery into the brain in an appropriate therapeutic concentration.

Study of the mesopore size effect on the electrochemical capacitor behaviors of mesoporous carbon/quinone derivative hybrids

A quinone derivative, 2,5-dichloro-1,4-benzoquinone (DCBQ), is hybridized with MgO-templated mesoporous carbons (MgO-Cs) with the average pore sizes of 5, 10, and 30 nm through gas-phase adsorption. The resulting hybrids are used for aqueous electrochemical capacitor electrodes due to the reversible redox reaction of DCBQ within the mesopores when using an aqueous H2SO4 electrolyte. This hybridization method precisely controls the weight ratio of porous carbons and DCBQ, and therefore, facilitates the discussion of the correlations between the amount of adsorbed DCBQ and the electrochemical capacitor behaviors of the MgO-C/DCBQ hybrids. Irrespective of the pore size of the MgO-Cs, the volumetric capacitance increases with increasing DCBQ content at current densities of 0.05−0.5 A g−1 because the hybridization of the redox-active DCBQ with porous carbons is not accompanied by the volumetric expansion of porous carbon particles. However, the DCBQ contents above 6 mmol per 1 g of MgO-C results in the decrease of the capacitance retention in the high current density region of ~10 A g−1. Not all the hybridized DCBQ molecules contribute to the capacitance enhancement, and the increase of the DCBQ content leads to a gradual decrease of the utilization ratio. In addition, the average pore sizes of 5 and 10 nm do not show the significant difference in the utilization ratio, but the MgO-C with the average pore size of 30 nm shows a decrease of the utilization ratio in comparison with those of the other MgO-Cs. This hybridization is applicable to any porous carbons, and the commercial activated carbon containing mesopores is appropriate for preparing high-performance electrochemical capacitors, due to its low-cost, large surface area for accommodating a large amount of DCBQ, and the absence of large mesopores as large as 30 nm.

Alcohol Dehydrogenase Activity Converts 3″-Hydroxy-geranylhydroquinone to an Aldehyde Intermediate for Shikonin and Benzoquinone Derivatives in Lithospermum erythrorhizon.

Shikonin derivatives are red naphthoquinone pigments produced by several boraginaceous plants, such as Lithospermum erythrorhizon. These compounds are biosynthesized from p-hydroxybenzoic acid and geranyl diphosphate. The coupling reaction that yields m-geranyl-p-hydroxybenzoic acid has been actively characterized, but little is known about later biosynthetic reactions. Although 3″-hydroxy-geranylhydroquinone produced from geranylhydroquinone by CYP76B74 has been regarded as an intermediate of shikonin derivatives, the next intermediate has not yet been identified. This study describes a novel alcohol dehydrogenase activity in L. erythrorhizon cell cultures. This enzyme was shown to oxidize the 3″-alcoholic group of (Z)-3″-hydroxy-geranylhydroquinone to an aldehyde moiety concomitant with the isomerization at the C2'-C3' double bond from the Z-form to the E-form. An enzyme oxidizing this substrate was not detected in other plant cell cultures, suggesting that this enzyme is specific to L. erythrorhizon. The reaction product, (E)-3″-oxo-geranylhydroquinone, was further converted to deoxyshikonofuran, another meroterpenoid metabolite produced in L. erythrorhizon cells. Although nonenzymatic cyclization occurred slowly, it was more efficient in the presence of crude enzymes of L. erythrorhizon cells. This activity was detected in both shikonin-producing and nonproducing cells, suggesting that the aldehyde intermediate at the biosynthetic branch point between naphthalene and benzo/hydroquinone ring formation likely constitutes a key common intermediate in the synthesis of shikonin and benzoquinone products, respectively.

Synthesis of Quinone Derivatives of Benzannelated Heterocycles with Bridgehead Nitrogen

A facile synthesis of para-quinones derived from fused benzimidazoles with a bridgehead nitrogen atom was developed. The heterocyclic quinone core formed as a result of reductive cyclization of ortho-nitroarenes containing alicyclic and aromatic azaheterocycles. Functionalization of 1,2,3,4-tetrahydro- and pyrido[1,2-a]benzimidazoles via SEAr, condensation, and reduction reactions allowed synthesis of amino derivatives which were oxidized with KNO3 in H2SO4 to obtain novel heterocyclic quinones.

Single‐Molecule Redox‐Targeting Reactions for a pH‐Neutral Aqueous Organic Redox Flow Battery

AbstractAqueous organic redox flow batteries (AORFBs) have received considerable attention for large‐scale energy storage. Quinone derivatives, such as 9,10‐anthraquinone‐2,7‐disulphonic acid (2,7‐AQDS), have been explored intensively owing to potentially low cost and swift reaction kinetics. However, the low solubility in pH‐neutral electrolytes restricts their application to corrosive acidic or caustic systems. Herein, the single molecule redox‐targeting reactions of 2,7‐AQDS anolyte are presented to circumvent its solubility limit in pH‐neutral electrolytes. Polyimide was employed as a low‐cost high‐capacity solid material to boost the capacity of 2,7‐AQDS electrolyte to 97 Ah L−1. Through in situ FTIR spectroscopy, a hydrogen‐bonding mediated reaction mechanism was disclosed. In conjunction with NaI as catholyte and nickel hexacyanoferrate as the catholyte capacity booster, a single‐molecule redox‐targeting reaction‐based full cell with energy density up to 39 Wh L−1 was demonstrated.

Iridium‐Catalyzed Oxidative Annulation of 2‐Arylindoles with Benzoquinone Leading to Indolo[1,2‐f]phenanthridin‐6‐ols

AbstractAn iridium‐catalyzed oxidative [4+2] annulation reaction of 2‐arylindoles using quinone derivatives as C2 synthons has been developed. From this reaction, a series of diversely substituted indolo[1,2‐f]phenanthridine derivatives were synthesized in an efficient manner. Moreover, diverse transformations of the phenanthridine derivatives thus obtained have also been performed, which showcase the synthetic potential of the present protocol.magnified image

Characterization of the non-covalent docking motif in the isolated reactant complex of a double proton-coupled electron transfer reaction with cryogenic ion spectroscopy.

The solution kinetics of a proton-coupled electron transfer reaction involving two-electron oxidation of a Ru compound with concomitant transfer of two protons to a quinone derivative have been interpreted to indicate the formation of a long-lived intermediate between the reactants. We characterize the ionic reactants, products, and an entrance channel reaction complex in the gas phase using high-resolution mass spectrometry augmented by cryogenic ion IR photodissociation spectroscopy. Collisional activation of this trapped entrance channel complex does not drive the reaction to products but rather yields dissociation back to reactants. Electronic structure calculations indicate that there are four low-lying isomeric forms of the non-covalently bound complex. Comparison of their predicted vibrational spectra with the observed band pattern indicates that the C=O groups of the ortho-quinone attach to protons on two different -NH2 groups of the reactant scaffold, exhibiting strong O-H-N contact motifs. Since collisional activation does not lead to the products observed in the liquid phase, these results indicate that the reaction most likely proceeds through reorientation of the H-atom donor ligand about the metal center.

A Quinone-Based Electrode for High-Performance Rechargeable Aluminum-Ion Batteries with a Low-Cost AlCl3/Urea Ionic Liquid Electrolyte.

Intensive energy demand urges state-of-the-art rechargeable batteries. Rechargeable aluminum-ion batteries (AIBs) are promising candidates with suitable cathode materials. Owing to high abundance of carbon, hydrogen, and oxygen and rich chemistry of organics (structural diversity and flexibility), small organic molecules are good choices as the electrode materials for AIB. Herein, a series of small-molecule quinone derivatives (SMQD) as cathode materials for AIB were investigated. Nonetheless, dissolution of small organic molecules into liquid electrolytes remains a fundamental challenge. To nullify the dissolution problem effectively, 1,4-benzoquinone was integrated with four bulky phthalimide groups to form 2,3,5,6-tetraphthalimido-1,4-benzoquinone (TPB) as the cathode materials and assembled to be the AI/TPB cell. As a result, the Al/TPB cell delivered capacity as high as 175 mA h/g over 250 cycles in the urea electrolyte system. Theoretical studies have also been carried out to reveal and understand the storage mechanism of the TPB electrode.

Two copper (II) complexes derived from anthranilic acid and 4-iodo-anthranilic acid Schiff bases: Structural elucidation, halogen bonding interactions and catalytic study using 3,5-DTBC

Two monomeric copper complexes [Cu(Pymab)(CCl3COO)(H2O)].H2O (1) and [Cu(Pymaib)(H2O)Cl]2 (2) were synthesized by reacting copper (II) trichloroacetate and copper(II) chloride with the monobasic tridentate Schiff-Base ligands (HPymab = (E)-2-((pyridine-2-yl)methyleneamino)benzoic acid and HPymaib = 4-iodo-2-{(E)-[(pyridin-2-yl) methyleneamino}benzoic acid) and characterized by elemental analysis, IR, UV–Vis, mass spectrometry, CV and single crystal XRD analysis. Both complexes are monomeric in the solid state and in the solution as well. For both complexes, single crystal XRD indicates a distorted square pyramidal coordination geometry of the metal atoms. Both 1 and 2 behave as effective catalysts towards the oxidation of 3,5-di-tert-butyl catechol to the corresponding quinone derivative in aerial oxygen. The reactions follow the Michaelis-Menten enzymatic reaction kinetics with (kcat) values of 1452 h−1 and 1458 h−1 respectively in DMSO and 1590 h−1 and 1636 h−1 in THF respectively. In the solid state both compounds participate in halogen bonding interactions that have been studied using DFT calculations and the molecular electrostatic potential (MEP) and the noncovalent interaction plot index (NCI plot) computational tools.

Hetero-Diels-Alder Reactions of Quinone Methides: The Origin of the α-Regioselectivity of 3-Methylene-1,2,4-naphthotriones.

The regioselective formation of α- and β-lapachone via hetero-Diels-Alder reactions was investigated by experimental and computational approaches. The experimentally observed α-selectivity was explored in detail, revealing that the lower energy barrier for the formation of α-lapachone is a result of lower Pauli repulsion throughout the reaction path, when compared to the β-isomer. By comparing equivalent points on both α- and β-lapachone potential energy surfaces (PES), according to the activation strain model (ASM) and energy decomposition analysis (EDA), we were able to demonstrate that the Pauli repulsion term increases more significantly when going from reactants to TSβ than to TSα, resulting in lower interaction energy in the early stages of the reaction path and in a later transition state for β-lapachone. Moreover, we confirmed that regio- and diastereoselectivity trends previously reported for other quinone methide intermediates are also observed for 3-methylene-1,2,4-naphthotriones, such as small endo/exo diastereoselectivity, as well as pronounced ortho/meta regioselectivity for reactions performed with dienophile containing electron-releasing groups. The results presented here provide a deeper understanding of the reactivity of quinone methide derivatives, aiding the future rational design of the reaction condition, structural modification of possible quinone methide intermediates, and the development of more selective synthetic routes for quinone derivatives.

P-Benzoquinone as a Privileged Scaffold of Pharmacological Significance: A Review.

Quinones are a huge class of compounds with affluent and captivating chemistry. p-Benzoquinone (p-BNZ) or 1,4-Benzoquinone is the key structural motif of numerous biologically active synthetic and natural compounds. This draws interest in its biological exploration to assess prospective therapeutic implications. It possesses immense therapeutic potential depending on different substitutions. This moiety has a marvelous potential to regulate a varied range of different cellular pathways which can be investigated for various selective activities. p-Benzoquinones have been a requisite core for the development of novel therapeutic molecules with minimum side effects. In this review, various synthetic, pharmacological approaches and structure-activity relationship studies focusing on the chemical groups responsible for evoking the pharmacological potential of p-benzoquinone derivatives have been emphasized. Additionally, the compilation highlights the chemical, pharmaceutical and medicinal aspects of synthetic and natural benzoquinone derivatives. The natural occurrences of p-benzoquinone derivatives with different pharmacological significance have also been reported in this review.

Alternaria toxins as casein kinase 2 inhibitors and possible consequences for estrogenicity: a hybrid in silico/in vitro study

Emerging mycotoxins produced by Alternaria spp. were previously reported to exert cytotoxic, genotoxic, but also estrogenic effects in human cells. The involved mechanisms are very complex and not fully elucidated yet. Thus, we followed an in silico target fishing approach to extend knowledge on the possible biological targets underlying the activity of alternariol, taken as the signature compound of Alternaria toxins. Combining ligand-based screening and structure-based modeling, the ubiquitous casein kinase 2 (CK2) was identified as a potential target for the compound. This result was validated in a cell-free in vitro CK2 activity assay, where alternariol inhibited CK2 with an IC50 of 707 nM. As CK2 was recently discussed to influence estrogen receptor (ER) transcription and DNA-binding affinity, we assessed a potential impact on the mRNA levels of ERα or ERβ by qRT-PCR and on nuclear localization of the receptors by confocal microscopy, using estrogen-sensitive Ishikawa cells as a model. While AOH did not affect the transcription of ERα or ERβ, an increase in nuclear localization of ERα after incubation with 10 µM AOH was observed. However, this effect might be due to ER binding affinity and therefore estrogenicity of AOH. Furthermore, in silico docking simulation revealed not only AOH, but also a number of other Alternaria toxins as potential inhibitors of CK2, including alternariol monomethyl ether and the perylene quinone derivative altertoxin II (ATX-II). These findings were representatively confirmed in vitro for the perylene quinone derivative altertoxin II, which was found to inhibit the kinase with an IC50 of 5.1 µM. Taken together, we propose CK2 inhibition as an additional mechanism to consider in future studies for alternariol and several other Alternaria toxins.

Expedient Synthesis of Dihydroisoquinolines by Cascade Annulation of Nitrovinylbenzoquinone

Abstract1,2‐Dihydroisoquinolines are important building blocks of many natural products and phamarceuticals. In continuation of our ongoing research on transformations of quinone derivatives, herein we present a catalyst‐free cascade annulation of β‐enamino esters with 2‐(2‐nitrovinyl)‐1,4‐benzoquinone, which allowed for the synthesis of various novel 1,2‐dihydroisoquinoline derivatives in moderate to good yields (60 %–99 %). This method is applicable to a wide variety of β‐enamino esters. The structure of one product was determined by an x‐ray crystal analysis. Moreover, a plausible mechanism was proposed.

Naphthoquinones, benzoquinones, and anthraquinones: Molecular docking, ADME and inhibition studies on human serum paraoxonase-1 associated with cardiovascular diseases.

Paraoxonase-1 (PON1) has essential roles such as protecting low-density lipoprotein against detoxification and oxidation of highly toxic compounds. Quinones are a class of compounds and a type of plant-derived secondary metabolites. Here, PON1 was purified using very simple methods and evaluation of the interactions between the enzyme and some quinones. It was found that these quinones displayed effective inhibitor properties for PON1 with the IC50 values in the range of 3.27-82.90 μM and the K i values in the range of 2.50 ± 0.65 to 30.90 ± 7.20 μM. These quinones displayed distinct inhibition mechanisms. It was determined that except for 5-hydroxy-2-methyl-1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone all quinones exhibit competitive inhibition effects. Also, molecular docking and in silico ADME studies were performed. Usage of drugs including quinone derivatives in structure with biological activity would be hazardous in some cases.

Anti-melanoma potential of two benzoquinone homologues embelin and rapanone - a comparative in vitro study

Rapanone and embelin are simple alkyl benzoquinone derivatives, mainly distributed in the Primulaceae. They have an interesting scope of biological activities including cytotoxicity. As melanoma is one of the most common types of cancer, in many cases resistant to current treatment regimens, the aim of this study was to assess and compare anti-melanoma activity of the two benzoquinones. Cytotoxicity of both compounds towards different melanoma cell lines (A375, HTB140, WM793) and selectivity with respect to normal keratinocytes (HaCaT) were investigated. Furthermore, interactions with a reference chemotherapeutic, doxorubicine, were assessed. Finally, analysis of anti-inflammatory, antioxidant and anti-tyrosinase activities of both benzoquinones was conducted as well.Rapanone showed selective and higher than doxorubicine cytotoxic potential against primary melanoma cell line, WM793. Although embelin was also highly cytotoxic, its selectivity was much poorer. Interestingly, in case of HTB140 and HaCaT cell lines a combination of each benzoquinone with doxorubicine potentiated the cytotoxic potential in a synergistic manner. Embelin revealed higher albumin anti-denaturation potential than rapanone but lower than diclofenac sodium. Anti-hyaluronidase effect of both benzoquinones was higher than quercetin. Both compounds showed antioxidant potential although significantly lower as compared to vitamin C. Finally, neither embelin nor rapanone had any inhibitory effect on tyrosinase.