Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.442
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Chem Commun (Camb) ; 56(8): 1179-1182, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31868184

RESUMO

We report unprecedented Friedel-Crafts arylation of chlorofullerenes C60Cl6 and C70Cl8 with unprotected carboxylic acids as an efficient single-step synthesis of the inherently stable water-soluble fullerene derivatives. Using this method, a series of previously unaccessible compounds was obtained without chromatographic purification in almost quantitative yields. Promising anti-HIV activity comparable to characteristics of commercial drugs was demonstrated for some of these compounds.


Assuntos
Fármacos Anti-HIV/farmacologia , Ácidos Carboxílicos/farmacologia , Fulerenos/farmacologia , Água/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Derivados de Benzeno/síntese química , Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Linhagem Celular Tumoral , Fulerenos/química , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Solubilidade , Tiofenos/síntese química , Tiofenos/química , Tiofenos/farmacologia
2.
Chemosphere ; 237: 124546, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549658

RESUMO

The Fe-modified spherical meso-silica MCM-41 was synthesized via the base precipitation with Fe3+/urea, and the structure was characterized. Especially, the selective and enhanced adsorption characters and mechanism of the monosubstituted benzenes were investigated. The results showed that Fe modification increased the specific surface area of MCM-41 and retained the mesopore structure. Importantly, adsorption of the monosubstituted benzenes indicated that the adsorption behavior of the monosubstituted benzenes on the Fe-modified MCM-41 (Fe-MCM-41) was a monolayer adsorption on the heterogeneous surfaces, and it showed great selective adsorption towards aniline, and the maximum adsorption capacity of the Fe-MCM-41 towards aniline was 17.5 and 7.9 times of nitrobenzene and phenol. Additionally, the adsorption process and the isotherm of aniline conformed to the pseudo-second order kinetic mode and the Langmuir mode. The maximum adsorption capacity of the Fe-MCM-41 and the pure MCM-41 towards aniline were 17.9 and 1.9 mg g-1, which indicated that the Fe modification significantly enhanced the adsorption capacity of MCM-41 towards aniline. Mechanism analysis reveals that the selective adsorption of the monosubstituted benzenes was attributed to the electron donating/withdrawing capacity of the substituent groups on benzene ring. Due to the electron withdrawing capacity of O atom, the exposed Fe atom of the ferric oxide loaded in the Fe-MCM-41 gave a strong electrophilic surface, which electrostatically interacted with the electron donating group (amino) in aniline.


Assuntos
Derivados de Benzeno/química , Compostos Férricos/química , Dióxido de Silício/química , Adsorção , Compostos de Anilina/química , Benzeno/química , Nitrobenzenos/química , Fenol/química , Poluentes Químicos da Água/química
3.
Molecules ; 24(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561548

RESUMO

The n-paraphenylene family comprises chains of phenylene units linked together by C-C bonds that are between single- and double-bonded, and where n corresponds to the number of phenylene units. In this work, we compare the response of the optical properties of different phenylene arrangements. We study linear chains (LPP), cyclic systems (CPPs), and non-conjugated cyclic systems with two hydrogenated phenylenes (H4[n]CPP). Particularly, the systems of interest in this work are [6]LPP, [12]- and [6]CPP and H4[6]CPP. This work combines Raman and infrared spectroscopies with absorption and fluorescence (one- and two-photon excitations) measured as a function of pressure up to maximum of about 25 GPa. Unprecedented crystallographic pressure-dependent results are shown on H4[n]CPP, revealing intramolecular π-π interactions upon compression. These intramolecular interactions justify the H4[n]CPP singular optical properties with increasing fluorescence lifetime as a function of pressure.


Assuntos
Derivados de Benzeno/química , Modelos Químicos , Pressão , Ciclização , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
4.
Chem Biodivers ; 16(12): e1900313, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545879

RESUMO

Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance-modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub-inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69 mm). The evaluation of aminoglycoside antibiotic resistance-modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity in vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.


Assuntos
Alcaloides/química , Antibacterianos/química , Derivados de Benzeno/química , Cissampelos/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Derivados de Benzeno/isolamento & purificação , Derivados de Benzeno/farmacologia , Cissampelos/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Staphylococcus aureus/efeitos dos fármacos
5.
Artigo em Inglês | MEDLINE | ID: mdl-31500327

RESUMO

The adsorption of malachite green (MG) onto sodium dodecylbenzene sulfonate (SDBS)-modified sepiolite was investigated with respect to pH, oscillation rate, MG dosage and adsorbent dosage. The modification condition and modified sepiolite characterization were examined. The conditions of 100% cation exchange capacity (CEC), pH value of 9, contact time of 60 min and 25 °C were deemed as the optimal conditions. The interlayer spacing of sepiolite was expanded and the surface hydrophobicity improved due to the entering of SDBS into the interlayer structure of the sepiolite ore. This is probably the reason for its adsorption enhancement. The adsorption of malachite green by organic sepiolite is in line with the quasi-secondary kinetic model. The results from the regeneration procedure suggest that a superior regeneration property obtained with 0.2 mol/L HCl concentration.


Assuntos
Adsorção , Derivados de Benzeno/química , Recuperação e Remediação Ambiental/métodos , Silicatos de Magnésio/química , Corantes de Rosanilina/química , Poluentes Químicos da Água/química
6.
Chem Pharm Bull (Tokyo) ; 67(9): 1015-1018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474724

RESUMO

Thiocyanation of aromatic compounds has been investigated using the combination of 1-chloro-1,2-benziodoxol-3-(1H)-one (1) and (trimethylsilyl)isothiocyanate (TMSNCS). The reaction with electron rich aromatic compounds proceeded smoothly to provide the thiocyanated products in high yield, while electron deficient heteroaromatic compounds were not suitable for this reaction. In these reactions, the regioselectivity was generally high. Transformations of the products were also investigated to demonstrate the utility of the reaction. Based on NMR experiments, we propose that thiocyanogen chloride is generated in situ as an active species.


Assuntos
Derivados de Benzeno/química , Compostos Heterocíclicos/química , Isotiocianatos/química , Compostos de Trimetilsilil/química , Iodo/química , Estereoisomerismo
7.
Eur J Med Chem ; 181: 111573, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394463

RESUMO

The carbonic anhydrase (CA) inhibitory activity of newly synthesized compounds 4-21 against the human CA (hCA) isoforms I, II, IX, and XII was measured and compared to that of standard sulfonamide inhibitors, acetazolamide (AAZ) and SLC-0111. Among this series; benzensulfonamides 6-11 gave the best potent hCA inhibitors with inhibition constants (KIs) ranging from 81.9 to 456.6 nM (AAZ and SLC-0111: KIs, 250.0 and 5080 nM, respectively). Compounds 6-11 proved to be effective hCA II inhibitors (KIs, 8.9-51.5 nM); they were almost equally potent to AAZ (KI, 12.0 nM) and had superior potency to SLC-0111 (KI, 960.0 nM). For hCA IX inhibition, compounds 6-11 proved to be potent inhibitors, with KI values of 3.9-36.0 nM, which were greater than or equal to that of AAZ and greater than that of SLC-0111 (KIs, 25.0 and 45.0 nM, respectively). For hCA XII inhibitory activity, compounds 6-11 displayed effective inhibition with KI values ranging from 4.6 to 86.3 nM and were therefore comparable to AAZ and SLC-0111 (KIs, 5.7 and 4.5 nM, respectively). Molecular docking studies of compounds 6, 7, 10, and 11 were conducted using the crystal structures of hCA isozymes I, II, IX, and XII to study their binding interactions for further lead optimization.


Assuntos
Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Derivados de Benzeno/síntese química , Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/metabolismo , Anidrase Carbônica IX/antagonistas & inibidores , Anidrase Carbônica IX/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Anidrases Carbônicas/metabolismo , Humanos , Simulação de Acoplamento Molecular , Sulfonamidas/síntese química
8.
Chem Commun (Camb) ; 55(69): 10214-10217, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31380528

RESUMO

The l,d-transpeptidases (Ldts) are promising antibiotic targets for treating tuberculosis. We report screening of cysteine-reactive inhibitors against LdtMt2 from Mycobacterium tuberculosis. Structural studies on LdtMt2 with potent inhibitor ebselen reveal opening of the benzisoselenazolone ring by a nucleophilic cysteine, forming a complex involving extensive hydrophobic interactions with a substrate-binding loop.


Assuntos
Azóis/química , Azóis/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Mycobacterium tuberculosis/enzimologia , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Peptidil Transferases/antagonistas & inibidores , Antituberculosos/química , Antituberculosos/farmacologia , Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Cisteína/metabolismo , Humanos , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Peptidil Transferases/metabolismo , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
9.
Mini Rev Med Chem ; 19(18): 1544-1557, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31362687

RESUMO

Soluble Guanylate Cyclase (sGC) is the intracellular receptor of Nitric Oxide (NO). The activation of sGC results in the conversion of Guanosine Triphosphate (GTP) to the secondary messenger cyclic Guanosine Monophosphate (cGMP). cGMP modulates a series of downstream cascades through activating a variety of effectors, such as Phosphodiesterase (PDE), Protein Kinase G (PKG) and Cyclic Nucleotide-Gated Ion Channels (CNG). NO-sGC-cGMP pathway plays significant roles in various physiological processes, including platelet aggregation, smooth muscle relaxation and neurotransmitter delivery. With the approval of an sGC stimulator Riociguat for the treatment of Pulmonary Arterial Hypertension (PAH), the enthusiasm in the discovery of sGC modulators continues for broad clinical applications. Notably, through activating the NO-sGC-cGMP pathway, sGC stimulator and activator potentiate for the treatment of various diseases, such as PAH, Heart Failure (HF), Diabetic Nephropathy (DN), Systemic Sclerosis (SS), fibrosis as well as other diseases including Sickle Cell Disease (SCD) and Central Nervous System (CNS) disease. Here, we review the preclinical and clinical studies of sGC stimulator and activator in recent years and prospect for the development of sGC modulators in the near future.


Assuntos
Ativadores de Enzimas/química , Guanilato Ciclase/metabolismo , Derivados de Benzeno/química , Derivados de Benzeno/metabolismo , Derivados de Benzeno/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , GMP Cíclico/metabolismo , Ativadores de Enzimas/metabolismo , Ativadores de Enzimas/uso terapêutico , Guanilato Ciclase/química , Humanos , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/patologia , Óxido Nítrico/metabolismo
10.
Mini Rev Med Chem ; 19(18): 1531-1543, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31288716

RESUMO

The search for inhibitors of the Janus kinase family (JAK1, JAK2, JAK3 and TYK2) has been ongoing for several decades and has resulted in a number of JAK inhibitors being approved for use in patients, such as tofacitinib for the treatment of autoimmune diseases such as Rheumatoid Arthritis (RA). Although initially thought to be a JAK3 selective inhibitor, tofacitinib was subsequently found to possess significant activity to inhibit JAK1 and JAK2 which has contributed to some adverse side effects. A selective JAK3 inhibitor should only have an effect within the immune system since JAK3 is solely expressed in lymphoid tissue; this makes JAK3 a target of interest in the search for treatments of autoimmune diseases. A method to obtain selectivity for JAK3 over the other JAK family members, which has attracted more scientific attention recently, is the targeting of the active site cysteine residue, unique in JAK3 within the JAK family, with compounds containing electrophilic warheads which can form a covalent bond with the nucleophilic thiol of the cysteine residue. This review encompasses the historical search for a covalent JAK3 inhibitor and the most recently published research which hasn't been reviewed to date. The most important compounds from the publications reviewed the activity and selectivity of these compounds together with some of the more important biological results are condensed in to an easily digested form that should prove useful for those interested in the field.


Assuntos
Janus Quinase 3/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Amidas/química , Amidas/metabolismo , Amidas/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Derivados de Benzeno/química , Derivados de Benzeno/metabolismo , Derivados de Benzeno/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Humanos , Janus Quinase 3/metabolismo , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico
11.
Phys Chem Chem Phys ; 21(31): 17118-17125, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31339118

RESUMO

The electronic structural origin of the THz and IR spectral changes occurring upon halogen-bond formation is examined by employing the technique of electron density analysis. Theoretical calculations and analyses are conducted for the complexes of pentafluoroiodobenzene (C6F5I) and nitryl chloride (O2NCl) formed with other (halogen-bond accepting) molecules taken as typical examples. It is shown that, in the case of the C-I stretching mode of C6F5I appearing in the THz spectral region, the intensity enhancement occurring upon halogen-bond formation arises from the intermolecular charge flux and (together with the vibrational frequency) is correlated to the partial charge-transfer and covalent nature of the halogen bond. For the N-Cl stretching vibration of O2NCl, it is shown that the high-frequency shift occurring upon complex formation with NH3 arises mainly from the electrostatic effect, while the reduction of its IR intensity arises from the polarization effect and, to a larger extent, from the intermolecular charge flux. These results indicate, therefore, that there are some observable spectroscopic properties in the THz and IR region that are mainly controlled by (and, hence, shed light on) the partial charge-transfer and covalent nature of halogen bonding.


Assuntos
Halogênios/química , Modelos Moleculares , Derivados de Benzeno/química , Hidrocarbonetos Halogenados/química , Nitritos/química , Teoria Quântica , Espectrofotometria Infravermelho , Eletricidade Estática
12.
J Trace Elem Med Biol ; 55: 180-189, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345356

RESUMO

BACKGROUND: Gliomas are the most aggressive malignant tumors of the central nervous system. The diphenyl diselenide [(PhSe)2] is an organoselenium compound that has multiple pharmacological properties. Previous reports showed that (PhSe)2 nanoencapsulation potentiates its in vitro antitumoral action and reduces its toxicity. OBJECTIVE: In this sense, the current study was designed to further evaluate the (PhSe)2 antitumoral effect by a set of in vitro techniques using a glioma cell line as well as by an animal model of gliobastoma. METHODS: For the in vitro tests, the cell viability, propidium iodide uptake and nitrite levels of rat glioma C6 cells were determined after incubation with free (PhSe)2 or (PhSe)2-loaded nanocapsules (NC). The glioblastoma model was induced by implantation of C6 glioma cells in the right striatum of rats. Following, animals were submitted to a repeated intragastric administration treatment with (PhSe)2 or NC (PhSe)2 (1 mg/kg/day for 15 days) to assess the possible antitumor effect. MAIN FINDINGS: Both compound forms decreased the C6 glioma cells viability without causing any effect in astrocytes cells (healthy control). Importantly, the NC (PhSe)2 had superior cytotoxic effect than its free form and increased the nitrite content. Independent of the (PhSe)2 forms, the intragastric treatment reduced brain tumor size and caused neither alteration in the plasma renal and hepatic markers of function nor in the parameters of oxidative balance in brain, liver and kidneys. PRINCIPAL CONCLUSIONS: The (PhSe)2 nanoencapsulation improved its cytotoxic effect against C6 glioma cells and both compound forms attenuated the tumor development.


Assuntos
Antineoplásicos/farmacologia , Derivados de Benzeno/farmacologia , Modelos Animais de Doenças , Glioblastoma/tratamento farmacológico , Nanocápsulas/química , Compostos Organosselênicos/farmacologia , Animais , Antineoplásicos/química , Astrócitos/efeitos dos fármacos , Derivados de Benzeno/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma/patologia , Masculino , Nitritos/análise , Compostos Organosselênicos/química , Ratos , Ratos Wistar
14.
Eur J Med Chem ; 176: 326-342, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31112893

RESUMO

Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular disease, obesity, and diabetes. These receptors show a high degree of stereoselectivity towards several classes of drugs. This review covers the most relevant findings that have been made in the last decade and takes into consideration only those compounds in which stereochemistry led to unexpected results or peculiar interactions with the receptors. These cases are reviewed and discussed with the aim to show how enantiomeric recognition originates at the molecular level. The structural characterization by crystallographic methods and docking experiments of complexes formed by PPARs with their ligands turns out to be an essential tool to explain receptor stereoselectivity.


Assuntos
Derivados de Benzeno/química , Derivados de Benzeno/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Acetatos/química , Acetatos/metabolismo , Animais , Sítios de Ligação , Cristalografia por Raios X , Humanos , Indóis/química , Indóis/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Oxazóis/química , Oxazóis/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Receptores Ativados por Proliferador de Peroxissomo/antagonistas & inibidores , Receptores Ativados por Proliferador de Peroxissomo/química , Fenilpropionatos/química , Fenilpropionatos/metabolismo , Ligação Proteica , Estereoisomerismo , Relação Estrutura-Atividade , Tirosina/análogos & derivados , Tirosina/metabolismo
15.
Int J Mol Sci ; 20(10)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137489

RESUMO

In this work, we present the synthesis and biological evaluation of novel series of diamide-based benzenesulfonamides 5a-h as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. The target tumor-associated isoforms hCA IX and XII were undeniably the most affected ones (KIs: 8.3-123.3 and 9.8-134.5 nM, respectively). Notably, diamides 5a and 5h stood out as a single-digit nanomolar hCA IX inhibitors (KIs = 8.8 and 8.3 nM). The SAR outcomes highlighted that bioisosteric replacement of the benzylidene moiety, compounds 5a-g, with the hetero 2-furylidene moiety, compound 5h, achieved the best IX/I and IX/II selectivity herein reported with SIs of 985 and 13.8, respectively. Molecular docking simulations of the prepared diamides within CA IX active site revealed the ability of 5h to establish an additional H-bond between the heterocyclic oxygen and HE/Gln67. Moreover, benzenesulfonamides 5a, 5b and 5h were evaluated for their antitumor activity against renal cancer UO-31 cell line. Compound 5h was the most potent derivative with about 1.5-fold more enhanced activity (IC50 = 4.89 ± 0.22 µM) than the reference drug Staurosporine (IC50 = 7.25 ± 0.43 µM). Moreover, 5a and 5h were able to induce apoptosis in UO-31 cells as evidenced by the significant increase in the percent of annexinV-FITC positive apoptotic cells by 22.5- and 26.5-folds, respectively.


Assuntos
Antineoplásicos/síntese química , Anidrase Carbônica IX/antagonistas & inibidores , Inibidores da Anidrase Carbônica/síntese química , Sulfonamidas/química , Antineoplásicos/farmacologia , Derivados de Benzeno/química , Sítios de Ligação , Anidrase Carbônica IX/química , Anidrase Carbônica IX/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Linhagem Celular Tumoral , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica
16.
J Enzyme Inhib Med Chem ; 34(1): 999-1009, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072143

RESUMO

This study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. The results of optical turbidimetry revealed that the ethyl acetate extraction obtained from R. procumbens (L.) Nees could inhibit platelet aggregation. Gene chip was used to investigate differentially expressed genes. According to the results of the gene chip, the targets of compounds isolated from the ethyl acetate extraction were predicted by network pharmacology. Computational studies revealed that chinensinaphthol methyl ether and neojusticin B may target the integrin αIIbß3 protein. The results of Prometheus NT.48 and microscale thermophoresis suggested that the molecular interactions between the two compounds with purified integrin αIIbß3 protein in the optimal test conditions were coherent with the docking results. To our best knowledge, this is the first report to state that chinensinaphthol methyl ether and neojusticin B target the integrin αIIbß3 protein.


Assuntos
Acanthaceae/química , Derivados de Benzeno/farmacologia , Dioxolanos/farmacologia , Éteres/farmacologia , Lignanas/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Derivados de Benzeno/química , Derivados de Benzeno/isolamento & purificação , Dioxolanos/química , Dioxolanos/isolamento & purificação , Relação Dose-Resposta a Droga , Éteres/química , Éteres/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/química , Inibidores da Agregação de Plaquetas/isolamento & purificação , Testes de Função Plaquetária , Relação Estrutura-Atividade
17.
PLoS One ; 14(4): e0205626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31034521

RESUMO

2,2'-diselenyldibenzoic acid (DSBA) is a chemical probe produced to explore the pharmacological properties of diphenyldiselenide-derived agents with seleno-hormetic activity undergoing preclinical development. The present study was designed to verify in vivo the drug's properties and to determine mechanistically how these may mediate the protection of tissues against stress conditions, exemplified by ionizing radiation induced damage in mouse bone marrow. In murine bone marrow hematopoietic cells, the drug initiated the activation of the Nrf2 transcription factor resulting in enhanced expression of downstream stress response genes. This type of response was confirmed in human liver cells and included enhanced expression of glutathione S-transferases (GST), important in the metabolism and pharmacological function of seleno-compounds. In C57 BL/6 mice, DSBA prevented the suppression of bone marrow hematopoietic cells caused by ionizing radiation exposure. Such in vivo prevention effects were associated with Nrf2 pathway activation in both bone marrow cells and liver tissue. These findings demonstrated for the first time the pharmacological properties of DSBA in vivo, suggesting a practical application for this type of Se-hormetic molecules as a radioprotective and/or prevention agents in cancer treatments.


Assuntos
Derivados de Benzeno/farmacologia , Raios gama/efeitos adversos , Células-Tronco Hematopoéticas/metabolismo , Compostos Organosselênicos/farmacologia , Protetores contra Radiação/farmacologia , Animais , Derivados de Benzeno/química , Células-Tronco Hematopoéticas/patologia , Células Hep G2 , Humanos , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Organosselênicos/química , Protetores contra Radiação/química
18.
Chem Pharm Bull (Tokyo) ; 67(6): 587-593, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30944268

RESUMO

Formylations of fluorine-containing aromatic compounds with dichloromethyl alkyl ethers have been investigated. Dichloromethyl propyl ether and dichloromethyl butyl ether have been applied for the formylation of fluorine-containing anisoles to give the corresponding aldehydes in good yields. Application of these ethers is preferable to that of methyl ether, which is prepared from volatile methyl formate. Reaction of fluorine-containing phenols with these dichloromethyl alkyl ethers did not give salicylaldehyde derivatives, leading instead to corresponding aryl formates in high yields. A plausible mechanism is discussed.


Assuntos
Éter Bisclorometílico/química , Flúor/química , Aldeídos/química , Derivados de Benzeno/química , Éteres/química , Ácidos de Lewis/química
19.
Molecules ; 24(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003443

RESUMO

Feeding experiments with stable isotopes are helpful tools for investigation of metabolic fluxes and biochemical pathways. For assessing nitrogen metabolism, the heavier nitrogen isotope, [15N], has been frequently used. In plants, it is usually applied in form of [15N]-nitrate, which is assimilated mainly in leaves. Thus, methods for quantification of the [15N]-nitrate/[14N]-nitrate ratio in leaves are useful for the planning and evaluation of feeding and pulse-chase experiments. Here we describe a simple and sensitive method for determining the [15N]-nitrate to [14N]-nitrate ratio in leaves. Leaf discs (8 mm diameter, approximately 10 mg fresh weight) were sufficient for analysis, allowing a single leaf to be sampled multiple times. Nitrate was extracted with hot water and derivatized with mesitylene in the presence of sulfuric acid to nitromesitylene. The derivatization product was analyzed by gas chromatography-mass spectrometry with electron ionization. Separation of the derivatized samples required only 6 min. The method shows excellent repeatability with intraday and interday standard deviations of less than 0.9 mol%. Using the method, we show that [15N]-nitrate declines in leaves of hydroponically grown Crassocephalum crepidioides, an African orphan crop, with a biological half-life of 4.5 days after transfer to medium containing [14N]-nitrate as the sole nitrogen source.


Assuntos
Asteraceae/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nitratos/análise , Isótopos de Nitrogênio/química , Benzeno/química , Derivados de Benzeno/química , Calibragem , Dinitrobenzenos/química , Cinética , Extratos Vegetais/análise , Folhas de Planta/química , Padrões de Referência
20.
Dalton Trans ; 48(20): 6685-6689, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30997474

RESUMO

Bifunctional Lewis acidic group 15 compounds have emerged as appealing platforms for anion sensing and organocatalysis. As part of our interest in the chemistry of these compounds, we have now compared the catalytic properties of [o-(MePPh2)C6H4SbPh2]+ ([3]+), [o-(PPh2)C6H4SbPh3]+ ([4]+), [o-(MePPh2)C6H4SbPh3]2+ ([5]2+), and [o-C6H4(SbMePh2)2]2+ ([6]2+) using the transfer hydrogenation of 2-phenyl-quinoline and 3-bromoquinoline with a Hantzsch ester benchmark reactions. This study, which also involved an evaluation of the catalytic properties of [Ph4Sb]+ and [Ph3MeP]+, shows that antimony cations are generally more active than their phosphorus counterparts and neutral stiboranes. Our results also demonstrate that dicationic systems such as [6]2+ are superior activators.


Assuntos
Antimônio/química , Derivados de Benzeno/química , Ácidos de Lewis/química , Compostos Organometálicos/química , Compostos Organofosforados/química , Quinolinas/química , Boratos/química , Catálise , Cátions , Hidrogenação , Estrutura Molecular , Fosfinas/química , Estereoisomerismo , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA