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1.
Food Res Int ; 163: 112187, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596128

RESUMO

Quinones are electrophilic compounds that can undergo Michael addition or Schiff base reaction with nucleophilic amines, but the effect of temperature has not been systematically studied. The aim of this study was to characterize how temperature affects the reaction mechanism and kinetics of 4-methylbenzoquinone (4MBQ) with lysine (Lys), Nα-acetyl Lys or Nε-acetyl Lys. The products were identified and characterized by LC-MS/MS, which revealed formation of Michael addition products, Schiff base, and a di-adduct in Lys and Nα-acetyl Lys-containing reaction mixtures. The product profiles were not affected by temperature in the range of 15-100 °C. NMR analysis proved that Michael addition of Nα-acetyl Lys occurred on the C5 position of 4MBQ. Rate constants for the reactions studied by stopped-flow UV-vis spectrophotometry under pseudo-first-order conditions where the amines were present in excess in the range 15 °C to 45 °C showed the α-amino groups of Lys are more reactive than the ε-groups. The kinetics results revealed that the temperature dependence of reaction rates followed the Arrhenius law, with activation energies in the order: Lys < Nε-acetyl Lys < Nα-acetyl Lys. Our results provide detailed knowledge about the temperature dependence of the reaction between Lys residues and quinones under conditions relevant for storage of foods.


Assuntos
Lisina , Bases de Schiff , Lisina/química , Cromatografia Líquida , Temperatura , Espectrometria de Massas em Tandem , Aminas , Quinonas
2.
Sci Adv ; 9(2): eadd9688, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36638176

RESUMO

Plants use solar energy to power cellular metabolism. The oxidation of plastoquinol and reduction of plastocyanin by cytochrome b6f (Cyt b6f) is known as one of the key steps of photosynthesis, but the catalytic mechanism in the plastoquinone oxidation site (Qp) remains elusive. Here, we describe two high-resolution cryo-EM structures of the spinach Cyt b6f homodimer with endogenous plastoquinones and in complex with plastocyanin. Three plastoquinones are visible and line up one after another head to tail near Qp in both monomers, indicating the existence of a channel in each monomer. Therefore, quinones appear to flow through Cyt b6f in one direction, transiently exposing the redox-active ring of quinone during catalysis. Our work proposes an unprecedented one-way traffic model that explains efficient quinol oxidation during photosynthesis and respiration.


Assuntos
Citocromos b , Plastocianina , Citocromos b/metabolismo , Plastocianina/metabolismo , Microscopia Crioeletrônica , Complexo Citocromos b6f/química , Complexo Citocromos b6f/metabolismo , Oxirredução , Fotossíntese , Plantas/metabolismo , Quinonas , Transporte de Elétrons
3.
Environ Res ; 216(Pt 4): 114721, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343716

RESUMO

Wearing of vehicle parts could release many chemical additives into the environment, such as benzotriazoles (BTRs), benzothiazoles (BTHs), and p-phenylenediamines (PPDs), which are potentially toxic to wildlife and humans. This study investigated the occurrence, source, and risks of BTRs, BTHs, and PPDs in a source catchment providing water to Guangzhou, a megacity in South China, covering groundwater, surface water, and stormwater. The results showed that BTRs and BTHs were predominant in surface water and groundwater. Unexpectedly, the BTR and BTH concentrations were lower in surface water than groundwater in a third of the paired samples. For the first time, 6PPD-quinone, a toxic ozonation product of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (6PPD), was extensively detected in source waters. Stormwater decreased the BTR concentrations but increased the 6PPD-quinone concentrations in surface water owing to their affiliation to suspended particles. From natural to urban segments of Liuxi river, a downstream increasing trend in BTR and BTH concentrations was observed, confirming that they are indicative of urban anthropogenic activities. Strong correlations between industrial activities and BTR or BTH concentrations in surface water indicated that industrial activities were their main sources. Six compounds were prioritized as potentially persistent, mobile, and toxic (PMT) chemicals, combing our monitoring results and REACH criterion. This study improves our understanding of the environmental fates and risks of water-soluble tire-wear chemicals, which provides important information for chemical management, and indicates attention should be paid to the risk posed by 6PPD-quinone in the source water.


Assuntos
Benzotiazóis , Poluentes Químicos da Água , Humanos , Benzotiazóis/toxicidade , Benzotiazóis/análise , Benzotiazóis/química , China , Monitoramento Ambiental , Fenilenodiaminas , Quinonas , Água , Poluentes Químicos da Água/análise , Cidades
4.
J Agric Food Chem ; 71(1): 331-346, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36538288

RESUMO

Pterostilbene (PTE), a dietary derivative of resveratrol, displayed pleiotropic health-promoting activities. This study aimed to explore the metabolic profiles and species differences of the phase I metabolism of PTE and to investigate subsequent detoxification after PTE bioactivation. PTE was found to be biotransformed to two pharmacologically active metabolites, pinostilbene and 3'-hydroxypterostilbene, in vivo and in vitro with substantial species differences. Human CYP1A2 was proved to be mainly responsible for the demethylation and 3'-hydroxylation of PTE, with its contribution to a demethylation of 94.5% and to a 3'-hydroxylation of 97.9%. An in vitro glutathione trapping experiment revealed the presence of an ortho-quinone intermediate formed by further oxidation of 3'-hydroxypterostilbene. Human glutathione S-transferase isoforms A2, T1, and A1 inactivated the ortho-quinone intermediate by catalyzing glutathione conjugation, implicating a potential protective pathway against PTE bioactivation-derived toxicity. Overall, this study provided a comprehensive view of PTE phase I metabolism and facilitated its further development as a promising nutraceutical.


Assuntos
Isoenzimas , Quinonas , Humanos , Resveratrol , Especificidade da Espécie , Glutationa/metabolismo
5.
J Bacteriol ; 205(1): e0038922, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36475831

RESUMO

Bacteroides species can use fumarate and oxygen as terminal electron acceptors during cellular respiration. In the human gut, oxygen diffuses from intestinal epithelial cells supplying "nanaerobic" oxygen levels. Many components of the anaerobic respiratory pathway have been determined, but such analyses have not been performed for nanaerobic respiration. Here, we present genetic, biochemical, enzymatic, and mass spectrometry analyses to elucidate the nanaerobic respiratory pathway in Bacteroides fragilis. Under anaerobic conditions, the transfer of electrons from NADH to the quinone pool has been shown to be contributed by two enzymes, NQR and NDH2. We find that the activity contributed by each under nanaerobic conditions is 77 and 23%, respectively, similar to the activity levels under anaerobic conditions. Using mass spectrometry, we show that the quinone pool also does not differ under these two conditions and consists of a mixture of menaquinone-8 to menaquinone-11, with menaquinone-10 predominant under both conditions. Analysis of fumarate reductase showed that it is synthesized and active under anaerobic and nanaerobic conditions. Previous RNA sequencing data and new transcription reporter assays show that expression of the cytochrome bd oxidase gene does not change under these conditions. Under nanaerobic conditions, we find both increased CydA protein and increased cytochrome bd activity. Reduced-minus-oxidized spectra of membranes showed the presence of heme d when the bacteria were grown in the presence of protoporphyrin IX and iron under both anaerobic and nanaerobic conditions, suggesting that the active oxidase can be assembled with or without oxygen. IMPORTANCE By performing a comprehensive analysis of nanaerobic respiration in Bacteroides fragilis, we show that this organism maintains capabilities for anaerobic respiration on fumarate and nanaerobic respiration on oxygen simultaneously. The contribution of the two NADH:quinone oxidoreductases and the composition of the quinone pool are the same under both conditions. Fumarate reductase and cytochrome bd are both present, and which of these terminal enzymes is active in electron transfer depends on the availability of the final electron acceptor: fumarate or oxygen. The synthesis of cytochrome bd and fumarate reductase under both conditions serves as an adaptation to an environment with low oxygen concentrations so that the bacteria can maximize energy conservation during fluctuating environmental conditions or occupation of different spatial niches.


Assuntos
Bacteroides fragilis , Succinato Desidrogenase , Humanos , Bacteroides fragilis/genética , Bacteroides fragilis/metabolismo , Anaerobiose , Succinato Desidrogenase/metabolismo , Vitamina K 2 , NAD/metabolismo , Transporte de Elétrons , Citocromos/metabolismo , Quinonas/metabolismo , Respiração , Oxigênio/metabolismo , Fumaratos/metabolismo
6.
Environ Int ; 171: 107715, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36577297

RESUMO

Tire wear particles (TWPs) enter road surface with the friction between tires and road surfaces. Under the volatilization, leaching, and transformation action on TWPs by sunlight and rain, tire additives are released into urban water systems, such as surface rainfall runoff, wastewater treatment plants (WWTPs), receiving surface waters, and drinking water treatment plant (DWTP). In this study, we investigated the occurrence of 23 tire additives and their transformation products in the urban water system of the Pearl River Delta region, South China. Nineteen target compounds were detected in the surface runoff, with 1,3-Diphenylguanidine (DPG) showing highest maximum concentration of 58780 ng/L. Benzothiazole and its transformation products are detected at the frequency of 100 % with the total concentrations of 480-42160 ng/L. The antioxidant derivative N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) was also detected up to 1562 ng/L, which was considerably higher than that of the parent compound 6PPD (the maximum concentration of 7.52 ng/L). Eleven and 8 compounds were detected in WWTPs influents and effluents, respectively, with removal rates of - 62-100 %. Seventeen compounds were detected in the receiving Zhujiang and Dongjiang rivers, while 9 compounds were detected in drinking water sources and DWTP samples. Road runoff, with total concentrations of target compounds up to 79200 ng/L, is suggested as the main non-point source for receiving rivers, while WWTPs effluents are the point sources due to incomplete removal of target compounds after accepting the initial runoff. 6PPD-Q and other 10 compounds displayed median to high ecological risks in surface waters, and the human daily intake of tire additives was estimated to be 2.63 × 10-8-3.16 × 10-5 mg/(kg d) via drinking water. This is the first report of the 6PPD-Q and 1,3-Diphenylurea levels in surface waters in China.


Assuntos
Água Potável , Poluentes Químicos da Água , Humanos , Poluentes Químicos da Água/análise , Rios , China , Quinonas , Monitoramento Ambiental
7.
J Hazard Mater ; 445: 130477, 2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-36493646

RESUMO

Pyrogenic carbon-mediated arsenite (As(III)) oxidation shows great potential as a prerequisite for the efficient removal of arsenic in groundwater. Herein, the critical role of N-containing functional groups in low and high-temperature prepared pyrogenic carbons for mediating As(III) oxidation was systemically explored from an electrochemistry perspective. The pyrogenic carbon electron donating capacity and area-normalized specific capacitance were the key parameters explained the As(III) oxidation kinetics mediated by low electrical conductive 500 °C biomass-derived pyrogenic carbons (N contents of 0.36-7.72 wt%, R2 = 0.87, p < 0.001) and high electrical conductive 800 °C pyrogenic carbons (N contents of 1.00-8.00 wt%, R2 = 0.99, p < 0.001), respectively. The production of H2O2 from the reaction between electron donating phenol groups or semiquinone radicals and oxygen, and the direct electron transfer between semiquinone radicals and As(III) contributed to these pyrogenic carbons mediated As(III) oxidation. While the electron accepting quinone, pyridinic-N, and pyrrolic-N groups did not significantly contribute to the 500 °C pyrogenic carbons mediated As(III) oxidation, the direct electron conduction by these functional groups was responsible for the facilitated As(III) oxidation by the 800 °C pyrogenic carbons. Furthermore, the pyridinic-N and pyrrolic-N groups showed higher electron conduction efficiency than that of the quinone groups. The findings help to develop robust pyrogenic carbons for As(III) contaminated groundwater treatment.


Assuntos
Arsenitos , Carbono , Temperatura , Peróxido de Hidrogênio , Pirólise , Oxirredução , Quinonas/química
8.
Chem Res Toxicol ; 36(1): 23-31, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36525601

RESUMO

Electrophilic quinones are produced during the combustion of gasoline in the atmosphere. Although these reactive species covalently bind to protein-based nucleophiles in cells, resulting in the formation of protein adducts involved in the modulation of redox signaling pathways and cytotoxicity, the extracellular regulation of quinones is not understood. In this study, incubation of 1,2-naphthoquinone (1,2-NQ) with the low-molecular-weight fraction of mouse plasma resulted in the consumption of cysteine (CysSH) in the plasma in a concentration-dependent manner. Covalent modification of albumin was markedly repressed by the addition of either the low-molecular-weight fraction of mouse plasma or CysSH, suggesting that CysSH protects by forming a conjugate with 1,2-NQ. Similar phenomena also occurred for other atmospheric quinones 1,4-NQ and 1,4-benzoquinone (1,4-BQ). The addition of cystine to a culture medium without amino acids enhanced the release of CysSH from A431 cells and blocked 1,2-NQ-mediated arylation of intracellular proteins, suggesting that 1,2-NQ interacts with extracellular CysSH. Liquid chromatography-tandem mass spectrometry analysis revealed that 1,2-NQ and 1,4-BQ undergoes nucleophilic attack by CysSH, yielding a 1,2-NQH2-SCys adduct and 1,4-BQH2-SCys adduct, respectively. Unlike 1,2-NQ and 1,4-BQ, the authentic 1,2-NQH2-SCys adduct and 1,4-BQH2-SCys adduct had little effect on the covalent modification of cellular proteins and viability of A431 cells. These results suggest that electrophilic quinones are readily trapped by CysSH released from A431 cells, forming less-toxic CysSH adducts and thereby repressing covalent modification of cellular proteins. These findings provide evidence for the existence of a "phase zero" reaction of electrophiles prior to their uptake by cells.


Assuntos
Naftoquinonas , Quinonas , Camundongos , Animais , Espaço Extracelular/metabolismo , Naftoquinonas/química , Proteínas , Transdução de Sinais
9.
Eur J Med Chem ; 246: 114926, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36508970

RESUMO

Quinones are attractive pharmacological scaffolds for developing new agents for the treatment of different transmissible and non-transmissible human diseases due to their capacity to alter the cell redox homeostasis. The bioactivity and potential mode of action of 19 p-quinone derivatives fused to different aromatic rings (carbo or heterocycles) and harboring distinct substituents were investigated in infective Trypanosoma brucei brucei. All the compounds, except for a furanequinone (EC50=38 µM), proved to be similarly or even more potent (EC50 = 0.5-5.5 µM) than the clinical drug nifurtimox (EC50 = 5.3 µM). Three furanequinones and one thiazolequinone displayed a higher selectivity than nifurtimox. Two of these selective hits resulted potent inhibitors of T. cruzi proliferation (EC50=0.8-1.1 µM) but proved inactive against Leishmania infantum amastigotes. Most of the p-quinones induced a rapid and marked intracellular oxidation in T. b. brucei. DFT calculations on the oxidized quinone (Q), semiquinone (Q•-) and hydroquinone (QH2) suggest that all quinones have negative ΔG for the formation of Q•-. Qualitative and quantitative structure-activity relationship analyses in two or three dimensions of different electronic and biophysical descriptors of quinones and their corresponding bioactivities (killing potency and oxidative capacity) were performed. Charge distribution over the quinone ring carbons of Q and Q.- and the frontier orbitals energies of SUMO (Q.-) and LUMO (Q) correlate with their oxidative and trypanocidal activity. QSAR analysis also highlighted that both bromine substitution in the p-quinone ring and a bulky phenyl group attached to the furane and thiazole rings (which generates a negative charge due to the π electron system polarized by the nearby heteroatoms) are favorable for activity. By combining experimental and in silico procedures, this study disclosed important information about p-quinones that may help to rationally tune their electronic properties and biological activities.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Nifurtimox/uso terapêutico , Quinonas/farmacologia , Doença de Chagas/tratamento farmacológico , Oxirredução , Simulação por Computador , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico
10.
Food Chem ; 408: 135242, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36566544

RESUMO

Polyphenol-protein reactions in model solutions of ß-lactoglobulin (ß-LG) incubated with (-)-epicatechin at 37 °C and 60 °C were monitored by microLC-timsTOF Pro-MS/MS combined with bioinformatics strategies. The addition of (-)-epicatechin to the model solutions resulted in changes in tryptic peptide profiles. Covalent bond formation between (-)-epicatechin o-quinones and ß-LG was identified for the residues S27, S30, K60, C66, K69, and C160, with C160 being the predominant binding site. Furthermore, the incubation of ß-LG with (-)-epicatechin significantly promoted oxidation, especially for the residues M7 and M24. The reaction of monomeric (-)-epicatechino-quinone at C160 was also identified in the milk chocolate sample. The adaptation of this study by extending the scope of the reaction products offers significant potential for comprehensive food profiling strategies.


Assuntos
Catequina , Lactoglobulinas , Lactoglobulinas/química , Espectrometria de Massas em Tandem , Oxirredução , Sítios de Ligação , Quinonas
11.
Pestic Biochem Physiol ; 188: 105227, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464347

RESUMO

Due to recent evidence of Aspergillus uvarum pathogenicity on wine grapes and variable fungicide sensitivity to quinone outside inhibitor (QoI) fungicides, the identity and QoI sensitivity of Aspergillus isolates from the Mid-Atlantic United States was investigated. Phylogenic analysis of 31 isolates revealed 26 as A. uvarum and 5 as A. japonicus, both of which have been previously isolated from grape. The A. uvarum isolates had variable sensitivities to the QoI azoxystrobin, and the genomic region that codes for the target of QoIs, cytochrome b, was sequenced. Translation of the cytochrome b coding sequence revealed that the most resistant isolates (termed cytb3) contained three mutations, S108A, F129L, and A194V, and the moderately sensitive isolates (termed cytb2) contained two mutations S108A and A194V. This is the first report of an amino acid variation in cytochrome b at position 108. Cytb3 isolates were significantly less inhibited than the cytb2 and wild-type isolates (cytbWT) in vitro, and were significantly less inhibited than the cytbWT isolates on detached fruit. Molecular docking analysis revealed similar differences, with azoxystrobin binding most securely in the cytbWT variant of cytochrome b than cytb2 and cytb3. As Aspergillus rot has not been a target disease of fungicide sprays in the U.S., the selection of resistant phenotypes is likely resultant from sprays for other diseases. Resistance is of concern due to the pathogenicity of A. uvarum and A. japonicus on wine grapes, and the ability of these species to be mycotoxigenic or pathogenic for humans.


Assuntos
Fungicidas Industriais , Vitis , Humanos , Estações do Ano , Citocromos b/genética , Simulação de Acoplamento Molecular , Aspergillus/genética , Fungicidas Industriais/farmacologia , Quinonas
12.
J Am Chem Soc ; 144(50): 22844-22849, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36508174

RESUMO

Inspired by a new biosynthetic hypothesis, we report a biomimetic total synthesis of atrachinenins A and B that explains their racemic nature. The synthesis exploits an intermolecular Diels-Alder reaction between a quinone meroterpenoid and E-ß-ocimene, followed by intramolecular (3 + 2) cycloaddition and a late-stage aerobic oxidation. Divergent transformations of a simple model system gave several complex polycyclic scaffolds, while also suggesting a structure revision for atrachinenin C.


Assuntos
Biomimética , Quinonas , Oxirredução , Ciclização , Reação de Cicloadição , Estereoisomerismo
13.
J Phys Chem B ; 126(46): 9549-9558, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36374126

RESUMO

In photosynthetic reaction centers from purple bacteria (PbRCs) and photosystem II (PSII), the photoinduced charge separation is terminated by an electron transfer between the primary (QA) and secondary (QB) quinones. Here, we investigate the electron transfer route, calculating the superexchange coupling (HQA-QB) for electron transfer from QA to QB in the protein environment. HQA-QB is significantly larger in PbRC than in PSII. In superexchange electron tunneling, the electron transfer via unoccupied molecular orbitals of the nonheme Fe complex (QA → Fe → QB) is pronounced in PbRC, whereas the electron transfer via occupied molecular orbitals (Fe → QB followed by QA → Fe) is pronounced in PSII. The significantly large HQA-QB is caused by a water molecule that donates the H-bond to the ligand Glu-M234 in PbRC. The corresponding water molecule is absent in PSII due to the existence of D1-Tyr246. HQA-QB increases in response to the Ser-L223···QB H-bond formation caused by an extension of the H-bond network, which facilitates charge delocalization over the QB site. This explains the observed discrepancy in the QA-to-QB electron transfer between PbRC and PSII, despite their structural similarity.


Assuntos
Elétrons , Quinonas , Quinonas/química , Transporte de Elétrons , Complexo de Proteína do Fotossistema II/metabolismo , Água
14.
Int J Mol Sci ; 23(22)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36430446

RESUMO

Lysyl oxidase-2 (LOXL2) is a Cu2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidase that catalyzes the oxidative deamination of peptidyl lysine and hydroxylysine residues to promote crosslinking of extracellular matrix proteins. LTQ is post-translationally derived from Lys653 and Tyr689, but its biogenesis mechanism remains still elusive. A 2.4 Å Zn2+-bound precursor structure lacking LTQ (PDB:5ZE3) has become available, where Lys653 and Tyr689 are 16.6 Å apart, thus a substantial conformational rearrangement is expected to take place for LTQ biogenesis. However, we have recently shown that the overall structures of the precursor (no LTQ) and the mature (LTQ-containing) LOXL2s are very similar and disulfide bonds are conserved. In this study, we aim to gain insights into the spatial arrangement of LTQ and the active site Cu2+ in the mature LOXL2 using a recombinant LOXL2 that is inhibited by 2-hydrazinopyridine (2HP). Comparative UV-vis and resonance Raman spectroscopic studies of the 2HP-inhibited LOXL2 and the corresponding model compounds and an EPR study of the latter support that 2HP-modified LTQ serves as a tridentate ligand to the active site Cu2. We propose that LTQ resides within 2.9 Å of the active site of Cu2+ in the mature LOXL2, and both LTQ and Cu2+ are solvent-exposed.


Assuntos
Lisina , Proteína-Lisina 6-Oxidase , Lisina/metabolismo , Proteína-Lisina 6-Oxidase/metabolismo , Domínio Catalítico , Quinonas/química
15.
Environ Sci Technol ; 56(23): 17029-17038, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36394988

RESUMO

Oxidative stress mediated by reactive oxygen species (ROS) is a key process for adverse aerosol health effects. Secondary organic aerosols (SOA) account for a major fraction of fine particulate matter, and their inhalation and deposition into the respiratory tract causes the formation of ROS by chemical and cellular processes, but their relative contributions are hardly quantified and their link to oxidative stress remains uncertain. Here, we quantified cellular and chemical superoxide generation by 9,10-phenanthrenequinone (PQN) and isoprene SOA using a chemiluminescence assay combined with electron paramagnetic resonance spectroscopy as well as kinetic modeling. We also applied cellular imaging techniques to study the cellular mechanism of superoxide release and oxidative damage on cell membranes. We show that PQN and isoprene SOA activate NADPH oxidase in macrophages to release massive amounts of superoxide, overwhelming the superoxide formation by aqueous chemical reactions in the epithelial lining fluid. The activation dose for PQN is 2 orders of magnitude lower than that of isoprene SOA, suggesting that quinones are more toxic. While higher exposures trigger cellular antioxidant response elements, the released ROS induce oxidative damage to the cell membrane through lipid peroxidation. Such mechanistic and quantitative understandings provide a basis for further elucidation of adverse health effects and oxidative stress by fine particulate matter.


Assuntos
Poluentes Atmosféricos , Superóxidos , Espécies Reativas de Oxigênio/metabolismo , Quinonas , NADPH Oxidases/metabolismo , NADPH Oxidases/farmacologia , Poluentes Atmosféricos/análise , Aerossóis , Material Particulado/toxicidade , Material Particulado/análise , Estresse Oxidativo , Macrófagos
16.
J Nat Prod ; 85(11): 2667-2674, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36346918

RESUMO

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.


Assuntos
Alternaria , Anti-Inflamatórios , Antivirais , Atriplex , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Perileno , Plantas Medicinais , Quinonas , Humanos , Alternaria/química , Alternaria/isolamento & purificação , Atriplex/microbiologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Estrutura Molecular , Perileno/química , Perileno/isolamento & purificação , Perileno/farmacologia , Plantas Medicinais/microbiologia , Quinonas/química , Quinonas/isolamento & purificação , Quinonas/farmacologia , Ácido Tenuazônico/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia
17.
Chem Commun (Camb) ; 58(95): 13238-13241, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36354976

RESUMO

A Pd-catalyzed direct method has been developed to access 1,3-disubstituted indolizines. This reaction proceeds through a regiospecific annulation of terminal alkynes with 2-pyridinyl-substituted p-quinone methides and, in most of the cases, the desired 1,3-disubstituted indolizines were obtained in moderate to good isolated yields. The control experiments suggested that the reaction does proceed through a substrate-controlled regiospecific formal [3 + 2]-annulation pathway.


Assuntos
Alcinos , Indolizinas , Catálise , Estrutura Molecular , Quinonas
18.
Nat Commun ; 13(1): 6633, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333313

RESUMO

The trans-clerodanes and sesquiterpene (hydro)quinones are a growing class of natural products that exhibit a wide range of biological activities. Although they are different types of natural products, some of them feature the same trans-decalin core structure. Here, we report the total syntheses of two members of trans-clerodanes, five members of sesquiterpene (hydro)quinones as well as the proposed structure of dysidavarone D via a modular synthetic route. A bioinspired tail-to-head cyclization strategy was developed to syntheses of the trans-decalin architectures by using two diastereochemically complementary radical polyene cyclization reactions catalyzed by Ti(III) and mediated by Mn(III), respectively. The different types of side chains were introduced by challenging nickel catalyzed reductive couplings of sterically hindered alkyl halides. The synthesis of the proposed dysidavarone D proved a wrong structural assignment of the natural product.


Assuntos
Produtos Biológicos , Diterpenos Clerodânicos , Sesquiterpenos , Ciclização , Quinonas/química , Estereoisomerismo , Catálise
19.
Analyst ; 147(23): 5264-5268, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36330961

RESUMO

NAD(P)H quinone oxidoreductase1 (NQO1) is a flavoenzyme that regulates the redox potential level in cells. Overexpression of NQO1 has been proven to be relevant to some malignant tumors. Herein a bioluminescent probe NQO1-Luc equipped with an NQO1-targeting group, trimethyl-locked quinone propionic acid (QPA), was constructed. The reduction of NQO1-Luc could be triggered by NQO1, resulting in the release of free D-luciferin, and concomitantly a bright bioluminescence emission. NQO1-Luc exhibits high selectivity and sensitivity toward NQO1 activity and the capability of distinguishing NQO1-overexpressing cells in vitro and in vivo, which offers a promising tool for investigations of NQO1 related biological processes including tumors in living organisms.


Assuntos
NAD(P)H Desidrogenase (Quinona) , Neoplasias , Humanos , NAD(P)H Desidrogenase (Quinona)/genética , Quinonas , Benzoquinonas
20.
Biochemistry ; 61(22): 2621-2627, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36322126

RESUMO

Photosynthetic reaction centers from a green sulfur bacterium (GsbRC), the PscA/PscA proteins, and photosystem I (PSI), PsaA/PsaB proteins, share structural similarities. Here, we report the redox potential (Em) values of GsbRC by solving the linear Poisson-Boltzmann equation and considering the protonation states of all titratable sites in the entire GsbRC protein and identify the factors that shift the Em values with respect to PSI. The Em values for one-electron reduction of the accessory (A-1) and adjacent (A0) chlorophylls in GsbRC are 100-250 mV higher than those in PSI, whereas the Em values for the Fe4S4 cluster (FX) are at the same level. The PsaA-Trp697/PsaB-Trp677 pair in PSI, which forms the A1-quinone binding site, is replaced with PscA-Arg638 in GsbRC. PsaB-Asp575 in PSI, which is responsible for the Em difference between A1A and A1B quinones in PSI, is absent in GsbRC. These discrepancies also contribute to the upshift in Em(A-1) and Em(A0) in GsbRC with respect to PSI. It seems likely that the upshifted Em for chlorophylls in GsbRC ultimately originates from the characteristics of the electrostatic environment that corresponds to the A1 site of PSI.


Assuntos
Elétrons , Complexo de Proteína do Fotossistema I , Transporte de Elétrons , Complexo de Proteína do Fotossistema I/metabolismo , Clorofila/metabolismo , Sítios de Ligação , Quinonas/química
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