Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.127
Filtrar
1.
Nat Commun ; 12(1): 2257, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859198

RESUMO

Naturally abundant quinones are important molecules, which play essential roles in various biological processes due to their reduction potential. In contrast to their universality, the investigation of reactions between quinones and proteins remains sparse. Herein, we report the development of a convenient strategy to protein modification via a biomimetic quinone-mediated oxidation at the N-terminus. By exploiting unique reactivity of an ortho-quinone reagent, the α-amine of protein N-terminus is oxidized to generate aldo or keto handle for orthogonal conjugation. The applications have been demonstrated using a range of proteins, including myoglobin, ubiquitin and small ubiquitin-related modifier 2 (SUMO2). The effect of this method is further highlighted via the preparation of a series of 17 macrophage inflammatory protein 1ß (MIP-1ß) analogs, followed by preliminary anti-HIV activity and cell viability assays, respectively. This method offers an efficient and complementary approach to existing strategies for N-terminal modification of proteins.


Assuntos
Antivirais/farmacologia , Materiais Biomiméticos/química , Biomimética/métodos , Quimiocina CCL4/farmacologia , Infecções por HIV/tratamento farmacológico , Aminas/química , Antivirais/química , Linhagem Celular Tumoral , Quimiocina CCL4/química , Quimiocina CCL4/genética , Quimiocina CCL4/isolamento & purificação , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Mioglobina/química , Oxirredução , Processamento de Proteína Pós-Traducional , Quinonas/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/química , Ubiquitina/química , Replicação Viral/efeitos dos fármacos
2.
Int J Mol Sci ; 22(6)2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33799456

RESUMO

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.


Assuntos
Antioxidantes/química , Cloroplastos/química , Quinonas/química , Terpenos/química , Cloroplastos/genética , Cromanos/química , Cromanos/metabolismo , Plastídeos/química , Plastídeos/genética , Quinonas/metabolismo , Espécies Reativas de Oxigênio/química , Terpenos/metabolismo
3.
Molecules ; 26(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801057

RESUMO

A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase IIα catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.


Assuntos
Canabidiol/análogos & derivados , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Experimentais , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Quinonas , Inibidores da Topoisomerase II , Animais , Canabidiol/química , Canabidiol/uso terapêutico , DNA Topoisomerases Tipo II/metabolismo , Humanos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/enzimologia , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Quinonas/química , Quinonas/uso terapêutico , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/uso terapêutico
4.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916126

RESUMO

The present work aims at studying the possible biosynthesis of fagopyrin in buckwheat plants with an attempt to address the existing gaps. The developed method of differential spectrophotometry can be used for identification of naphthodianthrones fagopyrins. It was found that in the vegetative mass of buckwheat plants, fagopyrin precursor-2-(piperidine-2-yl)-emodindianthron could be present. As fagopyrin can be produced by light effect, the temperature factor may influence the formation of protofagopyrin in vitro. An optimum temperature range was estimated for protofagopyrin formation. A possible fagopyrin biosynthesis under in vitro conditions was suggested.


Assuntos
Quinonas/análise , Quinonas/química , Espectrofotometria Ultravioleta , Análise Espectral , Fagopyrum/química , Extratos Vegetais/análise , Extratos Vegetais/química , Análise Espectral/métodos , Temperatura
5.
J Nat Prod ; 84(2): 436-443, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33560122

RESUMO

A new axial chiral binaphtoquinone, hypocrellone (1), and a new perylenequinone, hypomycin F (2), were isolated from the stromata of Hypocrella bambusae, together with five known compounds, 3-7. The structures of 1 and 2 were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of 1 was determined by electronic circular dichroism data analysis, and the absolute configurations of 2 and 3 were determined by X-ray crystallography. The axial chirality of 7 was determined by UV-induced photooxidation from 4. Compounds 1, 4, and 5 showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC50 values of 0.17, 0.038, and 0.12 µM. Compounds 4 and 5 were also active against live SARS-CoV-2 infection with EC50 values of 0.22 and 0.21 µM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that 4 and 5 could bind with the receptor-binding domain of SARS-CoV-2 S protein to prevent its interaction with human angiotensin-converting enzyme II receptor. Our results revealed that 4 and 5 are potential SARS-CoV-2 entry inhibitors.


Assuntos
Hypocreales/química , Naftoquinonas/farmacologia , Perileno/análogos & derivados , Quinonas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Naftoquinonas/química , Perileno/química , Perileno/farmacologia , Quinonas/química , /fisiologia
6.
Molecules ; 26(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572779

RESUMO

Plants have been used for thousands of years for various purposes because they have a wide variety of activities with biological significance. Mexican oregano is an aromatic plant of great importance to Mexico and north of Jalisco state as a spice with important economic value. Chromatographic identification and quantification of phenolic compounds and evaluation of their antioxidant activity were important tools to obtain a better characterization of this spice. Phytochemical analysis indicated the presence of flavonoids, triterpenes, saponins, quinones and tannins, the latter at high concentrations. Through chromatographic assays of Mexican oregano extracts, 62 compounds were identified, the major ones being quantified as: taxifolin, apigenin 7-O-glucoside, phlorizin, eriodictyol, quercetin, naringenin, hispidulin, pinocembrin, galangin and genkwanin (compound for the first time reported for this species). The results can be useful as a precedent to establish the bases of new quality characterization parameters and they have also suggested that Mexican oregano contains a wide variety of compounds with untapped importance for the development of new high value-added products.


Assuntos
Antioxidantes/química , Origanum/química , Fenóis/química , Flavonoides/química , Humanos , Fenóis/classificação , Fenóis/isolamento & purificação , Extratos Vegetais/química , Quinonas/química , Saponinas/química , Taninos/química , Triterpenos/química
7.
Biochem Biophys Res Commun ; 540: 51-55, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445110

RESUMO

Nitrogen heterocycle small molecules display various pharmaceutically important bioactivities and have great potential in drug development and application. Microbes are an important source for discovering nitrogen heterocycle natural products, and the elucidation of their biosynthetic pathways in microbes facilitates genetic manipulation of new nitrogen heterocycle products. In this study, we isolated three isoquinolinequinones from a Streptomyces albus J1074 conjugant and identified their biosynthetic gene cluster in the S. albus J1074 genome. The function of the biosynthetic gene cluster was confirmed by heterologous expression of the gene cluster in S. coelicolor M1146. This study uncovered a new biosynthetic machinery to produce nitrogen heterocycle natural products in microbes.


Assuntos
Vias Biossintéticas/genética , Regulação Bacteriana da Expressão Gênica , Isoquinolinas/metabolismo , Família Multigênica/genética , Quinonas/metabolismo , Streptomyces/genética , Produtos Biológicos/metabolismo , Genes Bacterianos/genética , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Quinonas/química , Quinonas/isolamento & purificação , Microbiologia do Solo , Streptomyces/química , Streptomyces/metabolismo
8.
Eur J Med Chem ; 210: 113084, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333397

RESUMO

Atovaquone belongs to a naphthoquinone class of drugs and is used in combination with proguanil (Malarone) for the treatment of acute, uncomplicated malaria caused by Plasmodium falciparum (including chloroquine-resistant P. falciparum/P. vivax). Numerous quinone-derived compounds have attracted considerable attention in the last few decades due to their potential in antimalarial drug discovery. Several semi-synthetic derivatives of natural quinones, synthetic quinones (naphtho-/benzo-quinone, anthraquinones, thiazinoquinones), and quinone-based hybrids were explored for their in vitro and in vivo antimalarial activities. A careful literature survey revealed that this topic has not been compiled as a review article so far. Therefore, we herein summarise the recent discovery (the year 2009-2020) of quinone based antimalarial compounds in chronological order. This compilation would be very useful towards the exploration of novel quinone-derived compounds against malarial parasites with promising efficacy and lesser side effects.


Assuntos
Antimaláricos/farmacologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Quinonas/farmacologia , Antimaláricos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinonas/química , Relação Estrutura-Atividade
9.
J Am Chem Soc ; 142(51): 21243-21248, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33315385

RESUMO

Electrically conductive metal-organic frameworks (cMOFs) have become a topic of intense interest in recent years because of their great potential in electrochemical energy storage, electrocatalysis, and sensing applications. Most of the cMOFs reported hitherto are 2D structures, and 3D cMOFs remain rare. Herein we report FeTHQ, a 3D cMOF synthesized from tetrahydroxy-1,4-quinone (THQ) and iron(II) sulfate salt. FeTHQ exhibited a conductivity of 3.3 ± 0.55 mS cm-1 at 300 K, which is high for 3D cMOFs. The conductivity of FeTHQ is valence-dependent. A higher conductivity was measured with the as-prepared FeTHQ than with the air-oxidized and sodium naphthalenide-reduced samples.


Assuntos
Condutividade Elétrica , Estruturas Metalorgânicas/química , Quinonas/química , Eletroquímica , Ferro/química , Modelos Moleculares , Oxirredução
10.
Nat Commun ; 11(1): 4955, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009385

RESUMO

The light-harvesting-reaction center complex (LH1-RC) from the purple phototrophic bacterium Thiorhodovibrio strain 970 exhibits an LH1 absorption maximum at 960 nm, the most red-shifted absorption for any bacteriochlorophyll (BChl) a-containing species. Here we present a cryo-EM structure of the strain 970 LH1-RC complex at 2.82 Å resolution. The LH1 forms a closed ring structure composed of sixteen pairs of the αß-polypeptides. Sixteen Ca ions are present in the LH1 C-terminal domain and are coordinated by residues from the αß-polypeptides that are hydrogen-bonded to BChl a. The Ca2+-facilitated hydrogen-bonding network forms the structural basis of the unusual LH1 redshift. The structure also revealed the arrangement of multiple forms of α- and ß-polypeptides in an individual LH1 ring. Such organization indicates a mechanism of interplay between the expression and assembly of the LH1 complex that is regulated through interactions with the RC subunits inside.


Assuntos
Cálcio/metabolismo , Microscopia Crioeletrônica , Complexos de Proteínas Captadores de Luz/ultraestrutura , Peptídeos/metabolismo , Fotossíntese , Sequência de Aminoácidos , Bacterioclorofila A/metabolismo , Sítios de Ligação , Chromatiaceae/metabolismo , Detergentes/química , Dimerização , Complexos de Proteínas Captadores de Luz/química , Complexos de Proteínas Captadores de Luz/metabolismo , Lipídeos/química , Peptídeos/química , Quinonas/química
11.
Int J Syst Evol Microbiol ; 70(10): 5217-5225, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32816656

RESUMO

Two novel Gram-stain-negative, aerobic and non-motile rods bacteria, designated TQ8ST and ZH2ST, were isolated from salt marsh sediment collected from the Tibetan Plateau. Strain TQ8ST was found to grow at 10-40 °C (optimum, 30 °C), pH 6.0-11.0 (optimum, pH 8.0-9.0) and in the presence of 2-12 % (w/v) NaCl (optimum, 6-8 %). Strain ZH2ST was found to grow at 15-40 °C (optimum, 30 °C), pH 7.0-10.0 (optimum pH 9.0) and in the presence of 2-10 % (w/v) NaCl (optimum, 4-6 %). Phylogenetic analysis based on the 16S rRNA gene sequences showed that strains TQ8ST and ZH2ST shared 99.07 % sequence similarity between each other and were affiliated with the genus Halomonas, sharing 97.48 % and 97.41 % of sequence similarity to their closest neighbour Halomonas sulfidaeris Esulfide1T, respectively. DNA-DNA hybridization analyses showed 61.0 % relatedness between strains TQ8ST and ZH2ST. The average nucleotide identity and the average amino acid identity values between the two genomes were 92.33 and 92.84 %, respectively. The values between the two strains and their close phylogenetic relatives were all below 95 %. The major respiratory quinones of strain TQ8ST were Q-9 and Q-8, while that of ZH2ST was Q-9. The main fatty acids shared by the two strains were C18 : 1 ω6c and/or C18 : 1 ω7c, C16 : 1 ω6c and/or C16 : 1 ω7c, C16 : 0 and C12 : 0 3-OH. Strain ZH2ST can be distinguished from TQ8ST by a higher proportion of C19 : 0 cyclo ω8c. The G+C content of the genomic DNA of strains TQ8ST and ZH2ST were 57.20 and 57.14 mol%, respectively. On the basis of phenotypic distinctiveness and phylogenetic divergence, the two isolates are considered to represent two novel species of the genus Halomonas, for which the names Halomonas rituensis sp. nov (type strain TQ8ST=KCTC 62530T=CICC 24572T) and Halomonas zhuhanensis sp. nov (type strain ZH2ST=KCTC 62531T=CICC 24505T) are proposed.


Assuntos
Sedimentos Geológicos/microbiologia , Halomonas/classificação , Filogenia , Áreas Alagadas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Halomonas/isolamento & purificação , Hibridização de Ácido Nucleico , Quinonas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Tibet
12.
Nat Commun ; 11(1): 4135, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811817

RESUMO

Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.


Assuntos
Complexo I de Transporte de Elétrons/química , Simulação de Dinâmica Molecular , Quinonas/química , Thermus thermophilus/enzimologia , Regulação Alostérica , Proteínas de Bactérias/química , Microscopia Crioeletrônica , Cristalografia por Raios X , Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/ultraestrutura , Modelos Moleculares , NAD/química , NAD/metabolismo , Redes Neurais de Computação , Conformação Proteica , Prótons , Quinonas/metabolismo , Thermus thermophilus/genética
13.
Ecotoxicol Environ Saf ; 202: 110859, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574861

RESUMO

The effects of quinoid compounds on azo dyes decolorization were studied. Compared with other quinones, menadione was the most effective at aiding azo dye decolorization. Sodium formate was a suitable carbon source for the anaerobic decolorization system. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis indicated that the microbial structure changed in response to varying carbon sources. Phylogenetic analysis showed that the anaerobic sludge was consisted mainly of nine genera. The mechanism studies showed that the biotransformation of menadione to its hydroquinone form was the rate-limiting step in the dye decolorization process. Moreover, study of the electron transfer mechanism of quinone-mediated reduction showed that azo dye decolorization is not a specific reaction. The NADH chain was involved in the decolorization process. The methane production test indicated that azo dyes had an inhibitory effect on methane production. However, supplementation with a redox mediator could recover the inhibited methanogenesis. High-throughput sequencing analysis revealed that the methanogenic archaeal community was altered in the anaerobic sludge with or without azo dyes and the redox mediator.


Assuntos
Compostos Azo/metabolismo , Quinonas/metabolismo , Eliminação de Resíduos Líquidos , Anaerobiose , Compostos Azo/química , Benzoquinonas , Biotransformação , Catálise , Corantes/química , Metano/metabolismo , Oxirredução , Filogenia , Quinonas/química , Esgotos
14.
PLoS One ; 15(6): e0234215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502195

RESUMO

Bacterial histidine kinases (HKs) are considered attractive drug targets because of their ability to govern adaptive responses coupled with their ubiquity. There are several classes of HK inhibitors; however, they suffer from drug resistance, poor bioavailability, and a lack of selectivity. The 3D structure of Staphylococcus aureus HK was not isolated in high-resolution coordinates, precluding further disclosure of structure-dependent binding to the specific antibiotics. To elucidate structure-dependent binding, the 3D structure of the catalytic domain WalK of S. aureus HK was constructed using homology modeling to investigate the WalK-ligand binding mechanisms through molecular docking studies and molecular dynamics simulations. The binding free energies of the waldiomycin and its methyl ester analog were calculated using molecular mechanics/generalized born surface area scoring. The key residues for protein-ligand binding were postulated. The structural divergence responsible for the 7.4-fold higher potency of waldiomycin than that of its ester analog was clearly observed. The optimized 3D macromolecule-ligand binding modes shed light on the S. aureus HK/WalK-ligand interactions that afford a means to assess binding affinity to design new HK/WalK inhibitors.


Assuntos
Ésteres/química , Histidina Quinase/química , Histidina Quinase/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Quinonas/química , Quinonas/metabolismo , Staphylococcus aureus/enzimologia , Sequência de Aminoácidos , Conformação Proteica , Termodinâmica
15.
Br J Radiol ; 93(1111): 20200034, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32374626

RESUMO

Necrosis plays vital roles in living organisms which is related closely with various diseases. Non-invasively necrotic imaging can be of great values in clinical decision-making, evaluation of individualized treatment responses, and prediction of patient prognosis. This narrative review will demonstrate how the evolution of quinones for necrotic imaging has been promoted by searching for their active centers. In this review, we summarized the recent developments of various quinones with the continuous simplified π-conjugated cores in necrotic imaging and speculated their possible molecular mechanisms might be attributed to their intercalations with exposed DNA in necrotic tissues. We discussed their clinical challenges of necrotic imaging with quinones and their future translation studies deserved to be explored in personalized patient treatment.


Assuntos
Sondas Moleculares , Infarto do Miocárdio/patologia , Necrose/diagnóstico por imagem , Quinonas , Animais , Antraquinonas/química , Células/patologia , DNA/análise , Humanos , Sondas Moleculares/química , Infarto do Miocárdio/diagnóstico por imagem , Naftoquinonas/química , Quinonas/química , Quinonas/classificação , Ratos
16.
Proc Natl Acad Sci U S A ; 117(20): 10818-10824, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32371483

RESUMO

Recent advances in neutron crystallographic studies have provided structural bases for quantum behaviors of protons observed in enzymatic reactions. Thus, we resolved the neutron crystal structure of a bacterial copper (Cu) amine oxidase (CAO), which contains a prosthetic Cu ion and a protein-derived redox cofactor, topa quinone (TPQ). We solved hitherto unknown structures of the active site, including a keto/enolate equilibrium of the cofactor with a nonplanar quinone ring, unusual proton sharing between the cofactor and the catalytic base, and metal-induced deprotonation of a histidine residue that coordinates to the Cu. Our findings show a refined active-site structure that gives detailed information on the protonation state of dissociable groups, such as the quinone cofactor, which are critical for catalytic reactions.


Assuntos
Amina Oxidase (contendo Cobre)/química , Proteínas de Bactérias/química , Quinonas/química , Domínio Catalítico , Coenzimas/química , Difração de Nêutrons , Prótons
17.
J Med Chem ; 63(10): 5568-5584, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32319768

RESUMO

Chemotherapy remains one of the dominant treatments to cure cancer. However, due to the many inherent drawbacks, there is a search for new chemotherapeutic drugs. Many classes of compounds have been investigated over the years to discover new targets and synergistic mechanisms of action including multicellular targets. In this work, we designed a new chemotherapeutic drug candidate against cancer, namely, [Ru(DIP)2(sq)](PF6) (Ru-sq) (DIP = 4,7-diphenyl-1,10-phenanthroline; sq = semiquinonate ligand). The aim was to combine the great potential expressed by Ru(II) polypyridyl complexes and the singular redox and biological properties associated with the catecholate moiety. Experimental evidence (e.g., X-ray crystallography, electron paramagnetic resonance, electrochemistry) demonstrates that the semiquinonate is the preferred oxidation state of the dioxo ligand in this complex. The biological activity of Ru-sq was then scrutinized in vitro and in vivo, and the results highlight the promising potential of this complex as a chemotherapeutic agent against cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/metabolismo , Quinonas/química , Quinonas/metabolismo , Rutênio/química , Rutênio/metabolismo , Animais , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Feminino , Células HeLa , Humanos , Ligantes , Camundongos , Camundongos Nus , Oxirredução/efeitos dos fármacos , Quinonas/farmacologia , Rutênio/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
18.
Food Chem ; 322: 126754, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32283367

RESUMO

During storage of coffee, the key aroma 2-furfurylthiol becomes less active, the mechanisms of this loss and ways to mitigate it were investigated. Aroma profiles were analyzed using GC-MS and sensory properties were evaluated by Quantitative Descriptive Analysis. Quinones, as the oxidation products of hydroxydroquinone, was found to actively bind 2-furfurylthiol, which accounted for the loss of 2-furfurylthiol. To mitigate this loss, ingredients were screened for their ability to prevent 2-furfurylthiol from loss. Cysteine had the highest 2-furfurylthiol releasing efficiency and ascorbic acid was also selected due to its 2-furfurylthiol releasing ability in Fenton reaction system. Concentrations were optimized and the addition of 0.045 g/L cysteine and 0.05 g/L ascorbic acid directly protected aroma during storage, these included 2-furfurylthiol, dimethyltrisulfide, methyl furfuryl disulfide, 4-ethylguaiacol and 4-vinylguaiacol. Ultimately, sensory testing showed a direct enhancement in nutty, sulfurous and roasted aroma attributes, an increase in flavour intensity and preference over shelf life.


Assuntos
Café/química , Furanos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Compostos de Sulfidrila/metabolismo , Compostos Orgânicos Voláteis/análise , Ácido Ascórbico/química , Café/metabolismo , Culinária/métodos , Cisteína/química , Armazenamento de Alimentos , Furanos/química , Análise dos Mínimos Quadrados , Quinonas/química , Quinonas/metabolismo , Compostos de Sulfidrila/química , Paladar , Compostos Orgânicos Voláteis/química
19.
Food Chem ; 317: 126454, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113140

RESUMO

The reaction efficiency of o-benzoquinones with amines (L-lysine, Nα-acetyl-L-lysine, glycine, L-methionine and L-arginine), thiols (L-cysteine and Nα-acetyl-L-cysteine) and protein (bovine serum albumin) were determined at pH 5.0, 7.0 and 8.0 and scan rate of 10, 50 and 100 mV/s by cyclic voltammetry. Nucleophiles containing multiple nucleophilic groups and nucleophilic group possessing low pKa value would enhance the reactivity of nucleophiles towards o-benzoquinones. The reactivity of different o-benzoquinones with L-lysine/L-cysteine followed the order: protocatechuic acid quinone ≈ catechol quinone > 4-methylbenzoquinone ≈ caffeic acid quinone > rosmarinic acid quinone > chlorogenic acid quinone. The reactivity of quinones would be decreased by the steric hindrance of substituents on quinone ring, and it would also be weakened by enhancing electron cloud density of quinone ring. Adducts generated by the interaction of 4-methylbenzoquinone with amines and thiols were tentatively identified as amine-quinone adduct and thiol-phenol adduct respectively by UPLC-QTOF-MS/MS and cyclic voltammetry.


Assuntos
Aminoácidos/química , Benzoquinonas/química , Técnicas Eletroquímicas/métodos , Aminas/química , Catecóis/química , Cromatografia Líquida , Cisteína/química , Hidroxibenzoatos/química , Fenóis , Quinonas/química , Compostos de Sulfidrila/química , Espectrometria de Massas em Tandem
20.
Biochim Biophys Acta Proteins Proteom ; 1868(6): 140412, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32179183

RESUMO

Matrix metalloproteinases (MMPs) are zinc-dependent extracellular matrix remodeling endopeptidases. MMPs cleave various matrix proteins such as collagen, elastin, gelatin and casein. MMPs are often implicated in pathological processes, such as cancer progression including metastasis. Meanwhile, microorganisms produce various secondary metabolites having unique structures. We designed and synthesized dehydroxymethylepoxyquinomicin (DHMEQ) based on the structure of epoxyquinomicin C derived from Amycolatopsis as an inhibitor of NF-κB. This compound inhibited cancer cell migration and invasion. Since DHMEQ is comparatively unstable in the body, we designed and synthesized a stable DHMEQ analog, SEMBL. SEMBL also inhibited cancer cell migration and invasion. We also looked for inhibitors of cancer cell migration and invasion from microbial culture filtrates. As a result, we isolated a known compound, ketomycin, from Actinomycetes. DHMEQ, SEMBL, and ketomycin are all NF-κB inhibitors, and inhibited the expression of MMPs in the inhibition of cellular migration and invasion. These are all compounds with comparatively low toxicity, and may be useful for the development of anti-metastasis agents.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/antagonistas & inibidores , Cicloexanonas/antagonistas & inibidores , Metaloproteinases da Matriz/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Actinobacteria/metabolismo , Animais , Antineoplásicos/química , Benzamidas/síntese química , Benzamidas/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cicloexanonas/síntese química , Glioxilatos/antagonistas & inibidores , Glioxilatos/metabolismo , Humanos , Metaloproteinase 11 da Matriz/efeitos dos fármacos , Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Modelos Moleculares , Subunidade p50 de NF-kappa B/metabolismo , Invasividade Neoplásica , Neoplasias , Quinonas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...