Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 595
Filtrar
1.
Molecules ; 27(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35889499

RESUMO

The phytochemical investigation of Placolobium vietnamense stems led to the isolation of a new isoflavone derivative (1) and three new benzil derivatives (2-4), together with four known pyranoisoflavones (5-8). The structures of all isolated compounds were determined on the basis of extensive spectroscopic analyses, including NMR and HRMS spectral data, as well as comparison of their spectroscopic data with those reported in the literature. The cytotoxicity of all isolated compounds was assessed against the human liver hepatocellular carcinoma (Hep G2) cell line, and compound 1 displayed the most significant cytotoxicity with an IC50 value of 8.0 µM. Furthermore, all isolated compounds were also tested for their inhibitory activity against NO production in RAW 264.7 macrophages. Of these, compound 1 exhibited the strongest inhibitory efficacy against the LPS-induced NO production with the IC50 value of 13.7 µM.


Assuntos
Antineoplásicos , Isoflavonas , Linhagem Celular Tumoral , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Estrutura Molecular , Fenilglioxal/análogos & derivados
2.
Photochem Photobiol Sci ; 21(5): 695-703, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34792791

RESUMO

The catalyst-free [2 + 2] photocycloaddition between benzils and simple olefins is reported. The adoption of visible light proved essential for the transformation, as shorter wavelengths led to uncontrolled decomposition. When cyclic olefins were used, the reaction occurred smoothly to afford the expected oxetanes regio- and stereoselectively after 24 h of irradiation. In contrast, in the case of acyclic olefins, longer reaction times were typically required and small amounts (ca. 20%) of [4 + 2] photocycloadducts and by-products deriving from competitive hydrogen atom abstraction were observed. The selectivity of the transformation could be consistently improved by decreasing the reaction temperature, thus restoring the desired [2 + 2] reactivity. An overall mechanistic picture is also offered based on the chemical and photophysical quenching experiments and the stereochemical output is rationalized based on Griesbeck models.


Assuntos
Alcenos , Luz , Alcenos/química , Fenilglioxal/análogos & derivados , Fotoquímica , Estereoisomerismo
3.
Bioorg Chem ; 115: 105183, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34339978

RESUMO

In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Antioxidantes/química , Benzoína/análogos & derivados , Inibidores Enzimáticos/química , Fenilglioxal/análogos & derivados , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Benzoína/síntese química , Benzoína/farmacologia , Linhagem Celular Tumoral , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Fenilglioxal/síntese química , Fenilglioxal/química , Fenilglioxal/farmacologia
4.
Molecules ; 26(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809372

RESUMO

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.


Assuntos
Aureobasidium/metabolismo , Benzoína/metabolismo , Benzoína/química , Biocatálise , Biotransformação , Concentração de Íons de Hidrogênio , Oxirredução , Fenilglioxal/análogos & derivados , Fenilglioxal/química , Fenilglioxal/metabolismo , Estereoisomerismo
5.
ACS Chem Biol ; 15(12): 3167-3175, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33249828

RESUMO

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a family of natural products defined by a genetically encoded precursor peptide that is processed by associated biosynthetic enzymes to form the mature product. Lasso peptides are a class of RiPP defined by an isopeptide linkage between the N-terminal amine and an internal Asp/Glu residue with the C-terminal sequence threaded through the macrocycle. This unique lariat topology, which typically provides considerable stability toward heat and proteases, has stimulated interest in lasso peptides as potential therapeutics. Post-translational modifications beyond the class-defining, threaded macrolactam have been reported, including one example of Arg deimination to yield citrulline (Cit). Although a Cit-containing lasso peptide (i.e., citrulassin) was serendipitously discovered during a genome-guided campaign, the gene(s) responsible for Arg deimination has remained unknown. Herein, we describe the use of reactivity-based screening to discriminate bacterial strains that produce Arg- versus Cit-bearing citrulassins, yielding 13 new lasso peptide variants. Partial phylogenetic profiling identified a distally encoded peptidyl arginine deiminase (PAD) gene ubiquitous to the Cit-containing variants. Absence of this gene correlated strongly with lasso peptide variants only containing Arg (i.e., des-citrulassin). Heterologous expression of the PAD gene in a des-citrulassin producer resulted in the production of the deiminated analog, confirming PAD involvement in Arg deimination. The PADs were then bioinformatically surveyed to provide a deeper understanding of their taxonomic distribution and genomic contexts and to facilitate future studies that will evaluate any additional biochemical roles for the superfamily.


Assuntos
Bactérias/enzimologia , Produtos Biológicos/química , Citrulina/análise , Desiminases de Arginina em Proteínas/metabolismo , Sondas Moleculares/química , Fenilglioxal/química , Filogenia , Processamento de Proteína Pós-Traducional , Desiminases de Arginina em Proteínas/classificação , Reprodutibilidade dos Testes
6.
J Org Chem ; 85(9): 5807-5814, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32250615

RESUMO

The synthesis of enantiomerically pure benzoins by hydrogenation of readily available benzils has been long thwarted by their base-sensitivity. We show here that an iron(II) hydride complex catalyzes the asymmetric transfer hydrogenation of benzils from 2-propanol. When strictly base-free conditions are granted, excellent enantioselectivity is achieved even with o-substituted substrates, which are particularly challenging to prepare with other methods. Hence, under optimized reaction conditions, chiral benzoins were prepared in good yields (up to 83%) and excellent enantioselectivity (up to 98% ee) in short reaction times (30-75 min). Also, this work confirms that both enantiomers of the benzoin products can be accessed when a metal catalyst is used, which is a clear advantage over enzymatic methods.


Assuntos
Benzoína , Fenilglioxal , Hidrogenação , Fenilglioxal/análogos & derivados , Estereoisomerismo
7.
Acta Crystallogr C Struct Chem ; 76(Pt 1): 44-63, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31919307

RESUMO

Eight novel Schiff bases derived from benzil dihydrazone (BDH) or benzil monohydrazone (BMH) and four fused-ring carbonyl compounds (3-formylindole, FI; 3-acetylindole, AI; 3-formyl-1-methylindole, MFI; 1-formylnaphthalene, FN) were synthesized and characterized by elemental analysis, ESI-QTOF-MS, 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. They are (1Z,2Z)-1,2-bis{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFI), C32H24N6, (1Z,2Z)-1,2-bis{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethane (BDHAI), C34H28N6, (1Z,2Z)-1,2-bis{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BMHMFI) acetonitrile hemisolvate, C34H28N6·0.5CH3CN, (1Z,2Z)-1,2-bis{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFN), C36H26N4, (Z)-2-{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFI), C23H17N3O, (Z)-2-{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethanone (BMHAI), C24H19N3O, (Z)-2-{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHMFI), C24H19N3O, and (Z)-2-{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFN) C25H18N2O. Moreover, the in vitro cytotoxicity of the eight title compounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four (BDHMFI, BDHFN, BMHMFI and BMHFN) are inactive and the other four (BDHFI, BDHAI, BMHFI and BMHAI) show severe toxicities against human A549 and mouse 4T1 cells, similar to the standard cisplatin. All the compounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex-dock function in SYBYL-X 2.0 software. Three target proteins, i.e. human ether-á-go-go-related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine-protein kinase PIM1, were chosen as the targets. Finally, the ligand-based structure-activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.


Assuntos
Proliferação de Células/efeitos dos fármacos , Fenilglioxal/análogos & derivados , Bases de Schiff/química , Animais , Linhagem Celular Tumoral , Cristalografia por Raios X/métodos , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Células NIH 3T3 , Fenilglioxal/química , Fenilglioxal/farmacologia , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
8.
Eur J Mass Spectrom (Chichester) ; 25(6): 457-462, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31547678

RESUMO

Competition experiments in which 1,2-phenylenediamine, C6H4(NH2)2, condenses with equimolar quantities of benzil, (C6H5CO)2, and a 3,3'- or 4,4'-disubstituted benzil (XC6H4CO)2 (X = F, Cl, Br, CH3 or CH3O) to form a mixture of 2,3-diphenylquinoxaline and the corresponding 2,3-diarylquinoxaline (Ar = XC6H4) in the microdroplets produced in a nebuliser allow a Hammett relationship with a ρ value of 1.85 to be developed for this accelerated condensation in the nebuliser. This structure reactivity relationship reveals that an appreciable amount of negative charge builds up on the carbon of the carbonyl group of the benzil during the rate-limiting step of the reaction, thus confirming that this process involves nucleophilic addition of the 1,2-phenylenediamine to the benzil. In general, the presence of an electron donating substituent, particularly in the 4 and 4' positions, in the benzil retards the reaction, whereas an electron attracting substituent, especially in the 3 and 3' position, accelerates it.


Assuntos
Quinoxalinas/química , Estrutura Molecular , Nebulizadores e Vaporizadores , Fenilenodiaminas/química , Fenilglioxal/análogos & derivados , Fenilglioxal/química
9.
Cell Chem Biol ; 26(9): 1229-1239.e9, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31231031

RESUMO

Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine (Lys) residue embedded in a dual variable domain (DVD)-IgG1 format can be assembled with high precision and efficiency under mild conditions. Here we show that replacing the Lys with an arginine (Arg) residue affords an orthogonal ADC assembly that is site-selective and stable. X-ray crystallography confirmed the location of the reactive Arg residue at the bottom of a deep pocket. As the Lys-to-Arg mutation is confined to a single residue in the heavy chain of the DVD-IgG1, heterodimeric assemblies that combine a buried Lys in one arm, a buried Arg in the other arm, and identical light chains, are readily assembled. Furthermore, the orthogonal conjugation chemistry enables the loading of heterodimeric DVD-IgG1s with two different cargos in a one-pot reaction and thus affords a convenient platform for dual-warhead ADCs and other multifaceted antibody conjugates.


Assuntos
Arginina/química , Imunoconjugados/química , Lisina/química , Anticorpos/química , Anticorpos/imunologia , Linhagem Celular , Cristalografia por Raios X/métodos , Haptenos/imunologia , Humanos , Imunoconjugados/imunologia , Imunoconjugados/ultraestrutura , Cadeias Leves de Imunoglobulina/química , Cadeias Leves de Imunoglobulina/imunologia , Cadeias Leves de Imunoglobulina/ultraestrutura , Fenilglioxal/química
10.
Org Biomol Chem ; 17(22): 5570-5577, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31114827

RESUMO

Nano drug delivery is a promising domain in biomedical theranostics and has aroused more and more attention in recent years. We report here an amphiphilic polymer TPG1, bearing a H2O2-sensitive benzil and an AIE fluorophore tetraphenylethene (TPE) unit, which is able to self-assemble into spherical nanosized micelles in aqueous solution. Doxorubicin (DOX) can be encapsulated into TPG1 micelles efficiently with the loading capability of up to 59% by weight. The benzil moiety could be cleaved via the Baeyer-Villiger type reaction in the presence of H2O2, leading to the decomposition of TPG1 micelles and release of DOX. In vitro studies indicated that DOX-loaded TPG1 micelles can be internalized by cancer cells, followed by unloading encapsulated DOX under the stimulation of H2O2. The drug release process can be monitored by the AIE fluorescence from the degradation products containing a TPE moiety. MTT assays against HeLa and HepG2 cancer cells demonstrated that DOX-loaded micelles showed good anticancer efficacy. The polymer TPG1 and the corresponding decomposed products showed great biocompatibility. Our data suggest that TPG1 has the potential to be employed for the controlled drug delivery system.


Assuntos
Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes/química , Peróxido de Hidrogênio/farmacologia , Fenilglioxal/análogos & derivados , Polímeros/farmacologia , Estilbenos/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Células HeLa , Células Hep G2 , Humanos , Peróxido de Hidrogênio/química , Micelas , Estrutura Molecular , Imagem Óptica , Fenilglioxal/química , Fenilglioxal/farmacologia , Polímeros/química
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 213: 235-248, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30695742

RESUMO

New mixed Fe(III) and Zn(II) complexes with isonitrosoacetophenone (HINAP) and l-amino acids (such as l-histidine, l-phenylalanine and l-proline) have been synthesized and characterized by elemental analyses, UV-Vis, IR and ESR spectroscopy and thermal analyses. The values of molar conductance of the complexes in DMSO solution at 10-3 M concentration indicate their non-electrolyte nature. IR spectroscopy has revealed the coordination of deprotonated ligands to metal through nitrogen and oxygen atoms in an N2O2 arrangement. Density functional theory (DFT) calculations were performed using the hybrid functional of Truhlar and Zhao (M06) with basis set of double zeta quality LANL2DZ to evaluate the cis and trans coordination modes and to ascertain dipole moment, HOMO-LUMO energy gap, chemical hardness, softness and electrophilicity. The magnetic moments and ESR measurements suggest that there is an admixture of S = 5/2 and S = 1/2 spins in Fe(III) complexes. UV-Visible spectra indicate a distorted octahedral geometry around the metal ions. Thermal analyses show the presence of hydrated and coordinated water. The antimicrobial activity was investigated against (G+ and G-) bacteria (Staphylococcus aureus, bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa) and fungi (Candida albicans). The iron and zinc complexes were found to be more active against Gram-positive than Gram negative bacteria. They also show considerable growth inhibition against the fungi tested. In vitro antitumor activity assayed against cancer cell lines of the HEP2 type (cancer cells of the larynx) exhibited significant toxicity of the ligands and their mixed complexes.


Assuntos
Aminoácidos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Teoria da Densidade Funcional , Ferro/química , Fenilglioxal/análogos & derivados , Zinco/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Bactérias/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Fungos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Fenilglioxal/síntese química , Fenilglioxal/química , Fenilglioxal/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Termogravimetria
12.
J Oleo Sci ; 67(9): 1123-1129, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30111681

RESUMO

Two novel types of non-aqueous bioconversion systems using fungal spores, either adsorbed on the surface of a filter pad or entrapped in calcium alginate beads, were constructed and applied for a model reaction: reduction of benzil to benzoin by Aspergillus sojae NBRC 32074. The spores adsorbed on a filter pad catalyzed the reduction in some toxic organic solvents, such as methylcyclohexane (log P: 3.61) and din-butyl ether (3.21). For the relationship between the reduction activity and the log P value of the organic solvent, a highly positive correlation (R2: 0.815) was observed. Surprisingly, the reduction proceeded in the more hydrophilic and toxic tert-butyl acetate (log P: 1.76). Glycerol was selected as the best hydride source. The higher the glycerol content, the more the benzoin was produced. While the production of benzil by spores was lower than that by mycelia in harmless di-n-hexyl ether (log P: 5.12), mycelia could not catalyze the reduction in the toxic tert-butyl acetate. In contrast, the spores entrapped in the calcium alginate beads could catalyze the reduction. Although the reduction by alginate-entrapped spores could be stably repeated 5 times in di-n-hexyl ether without a decline in the reduction activity, it was observed that the reduction activity of the spores gradually decreased after repeated reduction in tert-butyl acetate.


Assuntos
Reatores Biológicos , Esporos Fúngicos/metabolismo , Acetatos , Adsorção , Alginatos , Aspergillus , Benzoína , Reatores Biológicos/microbiologia , Catálise , Cicloexanos , Éteres , Ácido Glucurônico , Glicerol , Ácidos Hexurônicos , Interações Hidrofóbicas e Hidrofílicas , Fenilglioxal/análogos & derivados , Fenilglioxal/metabolismo , Solventes
13.
J Biol Chem ; 293(38): 14632-14645, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30093404

RESUMO

Modification with arginine-specific glyoxals modulates the permeability transition (PT) of rat liver mitochondria, with inhibitory or inducing effects that depend on the net charge of the adduct(s). Here, we show that phenylglyoxal (PGO) affects the PT in a species-specific manner (inhibition in mouse and yeast, induction in human and Drosophila mitochondria). Following the hypotheses (i) that the effects are mediated by conserved arginine(s) and (ii) that the PT is mediated by the F-ATP synthase, we have narrowed the search to 60 arginines. Most of these residues are located in subunits α, ß, γ, ϵ, a, and c and were excluded because PGO modification did not significantly affect enzyme catalysis. On the other hand, yeast mitochondria lacking subunit g or bearing a subunit g R107A mutation were totally resistant to PT inhibition by PGO. Thus, the effect of PGO on the PT is specifically mediated by Arg-107, the only subunit g arginine that has been conserved across species. These findings are evidence that the PT is mediated by F-ATP synthase.


Assuntos
Arginina/metabolismo , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Fenilglioxal/metabolismo , Saccharomyces cerevisiae/metabolismo , Animais , Cálcio/metabolismo , Catálise , Dimerização , Drosophila , Células HEK293 , Humanos , Camundongos , Mitocôndrias/enzimologia , Poro de Transição de Permeabilidade Mitocondrial , ATPases Mitocondriais Próton-Translocadoras/química , Especificidade da Espécie
14.
Org Biomol Chem ; 16(8): 1305-1311, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29388667

RESUMO

Here, we introduce 4-azidophenyl glyoxal (APG) as an efficient plug-and-play reagent for the selective functionalisation of arginine residues in native antibodies. The selective reaction between APG and arginines' guanidine groups allowed a facile introduction of azide groups on the monoclonal antibody trastuzumab (plug stage). These pre-functionalised antibody-azide conjugates were then derivatised during the "play stage" via a biorthogonal cycloaddition reaction with different strained alkynes. This afforded antibody-fluorophore and antibody-oligonucleotide conjugates, all showing preserved antigen selectivity and high stability in human plasma. Due to a lower content of arginines compared to lysines in native antibodies, this approach is thus attractive for the preparation of more homogeneous conjugates. This method proved to be orthogonal to classical lysine-based conjugation and allowed straightforward generation of dual-payload antibody.


Assuntos
Anticorpos Monoclonais/química , Arginina/química , Azidas/química , Fenilglioxal/análogos & derivados , Alcinos/química , Reação de Cicloadição , Imunoconjugados/química , Lisina/química , Fenilglioxal/química , Trastuzumab/química
15.
Bioorg Med Chem Lett ; 28(5): 969-973, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29439901

RESUMO

Peptidyl arginine deiminases (PADs) catalyze the post-translational deimination of peptidyl arginine residues to form citrulline residues. Aberrant citrullination of histones by one of the PAD isozymes, PAD4, is associated with various diseases, including rheumatoid arthritis, so high-throughput screening systems are needed to identify PAD4 inhibitors as chemical tools to investigate the role of PAD4, and as candidate therapeutic agents. Here, we utilized the addition-cyclization reaction between phenylglyoxal and citrulline under acidic conditions to design turn-on fluorescent probes for citrulline based on the donor-excited photoinduced electron transfer (d-PeT) mechanism. Among several derivatives of phenylglyoxal bearing a fluorescent moiety, we found that FGME enabled detection of citrulline without a neutralization process, and we used it to establish a simple methodology for turn-on fluorescence detection of citrulline.


Assuntos
Citrulina/análise , Corantes Fluorescentes/química , Fenilglioxal/química , Transporte de Elétrons , Fluorescência , Corantes Fluorescentes/síntese química , Estrutura Molecular , Fenilglioxal/síntese química , Processos Fotoquímicos
16.
Int J Biol Macromol ; 105(Pt 1): 171-182, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28687384

RESUMO

Human DHRS7 (SDR34C1) is one of insufficiently described enzymes of the short-chain dehydrogenase/reductase superfamily. The members of this superfamily often play an important pato/physiological role in the human body, participating in the metabolism of diverse substrates (e.g. retinoids, steroids, xenobiotics). A systematic approach to the identification of novel, physiological substrates of DHRS7 based on a combination of homology modeling, structure-based virtual screening and experimental evaluation has been used. Three novel substrates of DHRS7 (dihydrotestosterone, benzil and 4,4'-dimetylbenzil) have been described.


Assuntos
Oxirredutases/metabolismo , Di-Hidrotestosterona/metabolismo , Humanos , Simulação de Acoplamento Molecular , Oxirredutases/química , Fenilglioxal/análogos & derivados , Fenilglioxal/metabolismo , Ligação Proteica , Conformação Proteica
17.
Org Biomol Chem ; 15(22): 4867-4874, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28537302

RESUMO

Bromide mediated neighboring ester-participating bromocyclizations of o-alkynylbenzoates are described here for the synthesis of benzil-o-carboxylates. 4-bromoisocoumarins are also synthesized when phenyl o-alkynylbenzoate is used as the substrate. Mechanistic studies suggest that the whole process is composed of an electrophilic bromocyclization and a dibromohydration-based ring-opening, and the neighboring ester group participates in the bromocyclization. Interestingly, the two oxygen atoms of the keto carbonyls in benzil-o-carboxylates are both derived from water. The electrophilic bromo source is in situ generated from the oxidation of bromide.


Assuntos
Benzoatos/química , Ácidos Carboxílicos/síntese química , Ésteres/química , Isocumarinas/síntese química , Fenilglioxal/análogos & derivados , Ácidos Carboxílicos/química , Ciclização , Halogenação , Isocumarinas/química , Estrutura Molecular , Fenilglioxal/síntese química , Fenilglioxal/química
18.
Bioorg Chem ; 71: 325-334, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28285876

RESUMO

An efficient and simple one-pot synthesis of a new 1,2,3-triazole-1-oxide via reaction between isonitrosoacetophenone hydrazone and dipyridyl ketone in the EtOH/AcOH at room temperature has been developed smoothly in high yield. The reaction proceeds via metal salt free, in-situ formation of asymmetric azine followed by cyclization to provide 1,2,3-triazole 1-oxide compound. It has been structurally characterized. The 1:1 ratio reaction of the 1,2,3-triazole 1-oxide ligand with nickel(II) chloride gives the mononuclear complex [Ni(L)(DMF)Cl2], hexa-coordinated within an octahedral geometry. Characterization of the 1,2,3-triazole compound and its Ni(II) complex with FTIR, 1H and 13C NMR, UV-vis and elemental analysis also confirms the proposed structures of the compounds. The interactions of the compounds with Calf thymus DNA (CT-DNA) have been investigated by UV-visible spectra and viscosity measurements. The results suggested that both ligand and Ni(II) complex bind to DNA in electrostatic interaction and/or groove binding, also with a slight partial intercalation in the case of ligand. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H2O2). Both 1,2,3-triazole 1-oxide ligand and its nickel(II) complex show nuclease activity in the presence of hydrogen peroxide. DNA binding and cleavage affinities of the 1,2,3-triazole 1-oxide ligand is stronger than that of the Ni(II) complex.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Clivagem do DNA/efeitos dos fármacos , Níquel/química , Níquel/farmacologia , Triazóis/química , Triazóis/farmacologia , Animais , Bovinos , Técnicas de Química Combinatória/métodos , Complexos de Coordenação/síntese química , Cristalografia por Raios X , DNA/metabolismo , Hidrazonas/química , Modelos Moleculares , Fenilglioxal/análogos & derivados , Fenilglioxal/química , Triazóis/síntese química
19.
Physiol Plant ; 159(3): 340-353, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27787914

RESUMO

Miscanthus is a vigorous perennial Gramineae genus grown throughout the world as a promising bioenergy crop and generally regarded as heavy metal tolerant due to its ability to absorb heavy metals. However, little is known about the mechanism for heavy metal tolerance in Miscanthus. In this study, two Miscanthus species (Miscanthus sacchariflorus and Miscanthus floridulus) exhibiting different cadmium (Cd) sensitivity were used to address the mechanisms of Cd tolerance. Under the same Cd stress, M. sacchariflorus showed higher Cd tolerance with better growth and lower Cd accumulation in both shoots and roots than M. floridulus. The malate (MA) content significantly increased in root exudates of M. sacchariflorus following Cd treatment while it was almost unchanged in M. floridulus. Cellular Cd analysis and flux data showed that exogenous MA application markedly restricted Cd influx and accumulation while an anion-channel inhibitor (phenylglyoxal) effectively blocked Cd-induced MA secretion and increased Cd influx in M. sacchariflorus, indicating that MA secretion could alleviate Cd toxicity by reducing Cd uptake. The genes of malate dehydrogenases (MsMDHs) and Al-activated malate transporter 1 (MsALMT1) in M. sacchariflorus were highly upregulated under Cd stress, compared with that in M. floridulus. The results indicate that Cd-induced MA synthesis and secretion efficiently alleviate Cd toxicity by reducing Cd influx in M. sacchariflorus.


Assuntos
Cádmio/toxicidade , Malatos/metabolismo , Poaceae/fisiologia , Poluentes do Solo/toxicidade , Proteínas de Transporte de Ânions/antagonistas & inibidores , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Cádmio/metabolismo , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Malatos/farmacologia , Fenilglioxal/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Poaceae/citologia , Poaceae/efeitos dos fármacos , Poaceae/genética , Poluentes do Solo/metabolismo , Estresse Fisiológico
20.
Microb Pathog ; 100: 237-243, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27725279

RESUMO

Mononuclear transition metal complexes of Cu(II), Co(II) and Ni(II) with a newly synthesised macrocyclic ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and 1,2-diphenylethane-1,2-dione (2:2) have been synthesised. The synthesised compounds were characterised by various physical and spectroscopic techniques including elemental analysis, FTIR, Uv-Vis., 1H NMR, mass spectra, magnetic moment and XRD. The investigation of these macrocyclic complexes established that the stability of metal-ligand coordination through N atoms as tetradentate chelates. The metal/ligands ratio of 1:1 was proposed to afford octahedral geometry for the complexes. The antimicrobial activity of the compounds against some bacterial and fungal species were done by well diffusion method and the results shows that the metal complexes have a promising biological activity comparable with the parent ligand against all bacterial and fungal species. The antioxidant activity of the compounds was also studied through scavenging effect on DPPH radicals with the copper complex showing enhanced activity than other compounds. Additionally, the docking studies predicted the high antimicrobial activity due to the interaction of ligand with the protein.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Complexos de Coordenação/farmacologia , Hidrazinas/farmacologia , Compostos Macrocíclicos/farmacologia , Anti-Infecciosos/síntese química , Antioxidantes/síntese química , Bactérias/efeitos dos fármacos , Complexos de Coordenação/síntese química , Sequestradores de Radicais Livres/metabolismo , Fungos/efeitos dos fármacos , Hidrazinas/síntese química , Compostos Macrocíclicos/síntese química , Testes de Sensibilidade Microbiana , Fenilglioxal/análogos & derivados , Análise Espectral , Elementos de Transição
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...