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1.
Chem Commun (Camb) ; 55(58): 8494-8497, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31268095

RESUMO

A rational strategy was reported to construct boranil complexes (DPFB derivatives) with unique aggregation-induced emission effects by installing phenyl rings in the anil ligand as the intramolecular rotors. In view of the good biocompatibility and suitable lipophilicity, DPFB derivatives can serve as excellent fluorescent probes for specific imaging of lipid droplets in living cells and yolk lipids in zebrafish.


Assuntos
Compostos de Anilina/química , Compostos de Boro/química , Complexos de Coordenação/química , Corantes Fluorescentes/química , Gotículas Lipídicas/metabolismo , Compostos de Anilina/síntese química , Animais , Compostos de Boro/síntese química , Complexos de Coordenação/síntese química , Fluorescência , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Ligantes , Microscopia Confocal/métodos , Estrutura Molecular , Peixe-Zebra
2.
Eur J Med Chem ; 178: 214-231, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31185412

RESUMO

Discovery of antimicrobial agents with a novel model of action is in urgent need for the clinical management of multidrug-resistant bacterial infections. Recently, we reported the identification of a first-in-class bacterial ribosomal RNA synthesis inhibitor, which interrupted the interaction between the bacterial transcription factor NusB and NusE. In this study, a series of diaryl derivatives were rationally designed and synthesized based on the previously established pharmacophore model. Inhibitory activity against the NusB-NusE binding, circular dichroism of compound treated NusB, antimicrobial activity, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells were measured. Structure-activity relationship and quantitative structure-activity relationship were also concluded and discussed. Some of the derivatives demonstrated improved antimicrobial activity than the hit compound against a panel of clinically important pathogens, lowering the minimum inhibition concentration to 1-2 µg/mL against Staphylococcus aureus, including clinical strains of methicillin-resistant Staphylococcus aureus at a level comparable to some of the marketed antibiotics. Given the improved antimicrobial activity, specific inhibition of target protein-protein interaction and promising pharmacokinetic properties without significant cytotoxicity, this series of diaryl compounds have high potentials and deserve for further studies towards a new class of antimicrobial agents in the future.


Assuntos
Compostos de Anilina/farmacologia , Antibacterianos/farmacologia , Benzilaminas/farmacologia , Ligação Proteica/efeitos dos fármacos , Bases de Schiff/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Compostos de Anilina/toxicidade , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Proteínas de Bactérias/metabolismo , Benzilaminas/síntese química , Benzilaminas/química , Benzilaminas/toxicidade , Células CACO-2 , Desenho de Drogas , Eritrócitos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/toxicidade , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo
3.
Carbohydr Polym ; 216: 54-62, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047082

RESUMO

Biodegradable, antimicrobial, and semiconducting cellulosic composite was synthesized by in-situ polymerization of polyaniline in the presence of cellulose. The cobalt ferrite nanoparticles (CFO-NPs) were added during the polymerization process to acquire this composite magnetic property. The CFO-NPs were prepared by sol-gel method with average particles size less than 50 nm. The nanocomposites were characterized by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). In addition, their magnetic, dielectric constant, dielectric loss, and conductivity behaviors were studied. The magnetization (Ms) and conductivity increased up to 3.7 emu/g and 3.5 × 10-3 S/cm, respectively, with increasing CFO-NPs content. The prepared electromagnetic nanocomposite exhibits highly efficient biodegradability and antimicrobial activity against Escherichia coli, Bacillus subtilis, and Candida albicans. The antimicrobial activity increased with increasing CFO-NPs while the biodegradability decreased.


Assuntos
Compostos de Anilina/farmacologia , Celulose/farmacologia , Cobalto/farmacologia , Compostos Férricos/farmacologia , Nanocompostos/química , Nanopartículas/química , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacologia , Candida albicans/efeitos dos fármacos , Celulose/análogos & derivados , Celulose/síntese química , Cobalto/química , Condutividade Elétrica , Escherichia coli/efeitos dos fármacos , Compostos Férricos/síntese química , Compostos Férricos/química , Fenômenos Magnéticos , Tamanho da Partícula
4.
Mater Sci Eng C Mater Biol Appl ; 101: 243-253, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029317

RESUMO

Developing a simple produces for efficient derivation of motor neurons (MNs) is essential for neural tissue engineering studies. Stem cells with high capacity for neural differentiation and scaffolds with the potential to promote motor neurons differentiation are promising candidates for neural tissue engineering. Recently, human olfactory ecto-mesenchymal stem cells (OE-MSCs), which are isolated easily from the olfactory mucosa, are considered a new hope for neuronal replacement due to their neural crest origin. Herein, we synthesized conducting hydrogels using different concentration of chitosan-g-aniline pentamer, gelatin, and agarose. The chemical structures, swelling and deswelling ratio, ionic conductivity and thermal properties of the hydrogel were characterized. Scaffolds with 10% chitosan-g-aniline pentamer/gelatin (S10) were chosen for further investigation and the potential of OE-MSCs as a new source for programming to motor neuron-like cells investigated on tissue culture plate (TCP) and conductive hydrogels. Cell differentiation was evaluated at the level of mRNA and protein synthesis and indicated that conductive hydrogels significantly increased the markers related to motor neurons including Hb-9, Islet-1 and ChAT compared to TCP. Taken together, the results suggest that OE-MSCs would be successfully differentiated into motor neuron-like cells on conductive hydrogels and would have a promising potential for treating motor neuron-related diseases.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Quitosana/farmacologia , Condutividade Elétrica , Gelatina/farmacologia , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Neurônios Motores/citologia , Sefarose/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/farmacologia , Fosfatos de Cálcio/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quitosana/síntese química , Quitosana/química , Força Compressiva , Gelatina/química , Humanos , Hidrogéis/química , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Neurônios Motores/efeitos dos fármacos , Bulbo Olfatório/citologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Termogravimetria , Tecidos Suporte/química
5.
Photochem Photobiol Sci ; 18(6): 1447-1460, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30957809

RESUMO

Fluorescence change systems that can respond to biological objects have attracted attention for use as biological probes and sensors. In this study, we report emission enhancement in a fluorescent aggregate composed of amphiphilic donor-acceptor dye molecules. The emission efficiency of the aggregate was reduced upon introducing a hydrophilic galactopyranose moiety, because of the decrease in the aggregate stability, which in turn was due to disruption of the hydrophilicity-hydrophobicity balance. In contrast, emission enhancement could be achieved by treatment with ß-galactosidase, as a result of the removal of the galactopyranose moiety. The change in aggregate stabilization based on the hydrophilicity-hydrophobicity balance leads to the emission enhancement into detectable ß-galactosidase activity.


Assuntos
Compostos de Anilina/química , Fluorescência , Corantes Fluorescentes/química , Tensoativos/química , Tiadiazóis/química , beta-Galactosidase/análise , Compostos de Anilina/síntese química , Corantes Fluorescentes/síntese química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Espectrometria de Fluorescência , Tensoativos/síntese química , Tiadiazóis/síntese química , beta-Galactosidase/metabolismo
6.
Mater Sci Eng C Mater Biol Appl ; 100: 584-597, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948095

RESUMO

Parkinson's disease (PD) is a long-term neurodegenerative disorders that characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNc). Bone marrow stromal cells (BMSCs) are promising therapeutic agents for neurodegenerative disease due to their multipotent capacity. To promote the potential therapeutic effect of BMSCs on PD, we developed an injectable Gelatin-PANI hydrogels as a novel carrier for delivering BMSCs to the SNc region in mice with PD by stereotactic injection. Histology results showed that the BMSCs-loaded hydrogels lead to increased numbers of tyrosine hydroxylase positive (TH+) dopaminergic neurons and fibers in the SNc and striatum, and increased expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the SNc. Meanwhile, rotarod and open field evaluation demonstrated BMSCs-loaded hydrogels significantly improved the behavioral performance of PD mice. Importantly, BMSCs-loaded hydrogels imparted more sustained protective effects than BMSCs alone in PD mice. Overall, the current data indicate that the hydrogel serves as a promising carrier to deliver BMSCs to the SNc for the treatment of PD.


Assuntos
Portadores de Fármacos/química , Condutividade Elétrica , Gelatina/química , Hidrogéis/química , Injeções , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Doença de Parkinson/terapia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Compostos de Anilina/síntese química , Compostos de Anilina/química , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Sobrevivência Celular , Preparações de Ação Retardada/farmacologia , Neurônios Dopaminérgicos/patologia , Gelatina/síntese química , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Hidrogéis/síntese química , Masculino , Camundongos Endogâmicos C57BL , Doença de Parkinson/patologia , Reologia , Substância Negra/patologia
7.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022898

RESUMO

In this work, polyaniline (PANI) is synthesized via oxidative polymerization of aniline and purified using organic solvents where the emeraldine phase is isolated by employing a phase separation system. The above contributes to the increase in the percentage yield compared to previous works and the possibility of being used as a single phase. In addition, the PANI/AgNPs composite is prepared in situ at the polymerization of aniline, adding silver nitrate and glycine to create the AgNPs inside the PANI matrix by controlling the pH, temperature, time of reaction and incorporating a new purification technique.


Assuntos
Compostos de Anilina/síntese química , Solventes/química , Compostos de Anilina/química , Oxirredução , Polimerização , Nitrato de Prata/química
8.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022940

RESUMO

Light-driven phase change materials (PCMs) have received significant attention due to their capacity to convert visible light into thermal energy, storing it as latent heat. However, continuous photo-thermal conversion can cause the PCMs to reach high thermal equilibrium temperatures after phase transition. In our study, a novel light-driven phase change material system with temperature-control properties was constructed using a thermochromic compound. Thermochromic phase change materials (TC-PCMs) were prepared by introducing 2-anilino-6-dibutylamino-3-methylfluoran (ODB-2) and bisphenol A (BPA) into 1-hexadecanol (1-HD) in various proportions. Photo-thermal conversion performance was investigated with solar radiation (low power of 0.09 W/cm2) and a xenon lamp (at a high power of 0.14 W/cm2). The TC-PCMs showed a low equilibrium temperature due to variations in absorbance. Specifically, the temperature of TC-PCM180 (ODB-2, bisphenol A and 1-HD ratio 1:2:180) could stabilize at 54 °C approximately. TC-PCMs exhibited reversibility and repeatability after 20 irradiation and cooling cycles.


Assuntos
Compostos de Anilina/síntese química , Compostos Benzidrílicos/síntese química , Álcoois Graxos/síntese química , Fluoresceínas/síntese química , Fenóis/síntese química , Compostos de Anilina/química , Compostos de Anilina/efeitos da radiação , Compostos Benzidrílicos/química , Compostos Benzidrílicos/efeitos da radiação , Álcoois Graxos/química , Álcoois Graxos/efeitos da radiação , Fluoresceínas/química , Fluoresceínas/efeitos da radiação , Temperatura Alta , Luz , Transição de Fase/efeitos da radiação , Fenóis/química , Fenóis/efeitos da radiação , Temperatura Ambiente
9.
Chem Commun (Camb) ; 55(17): 2541-2544, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30742156

RESUMO

A novel near-infrared fluorescent light-up probe with a tumor-homing pentapeptide, CREKA (Cys-Arg-Glu-Lys-Ala), specifically binds to fibrin-fibronectin complexes was rationally designed and developed for biomedical imaging. Its superior practical applications in tumor imaging and drug-induced liver injury detection are well demonstrated for the first time.


Assuntos
Compostos de Anilina/química , Benzopiranos/química , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Células A549 , Compostos de Anilina/síntese química , Animais , Benzopiranos/síntese química , Tetracloreto de Carbono , Feminino , Fibrina/química , Fibronectinas/química , Corantes Fluorescentes/síntese química , Humanos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência/métodos , Oligopeptídeos/química
10.
Anal Chim Acta ; 1049: 74-81, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30612659

RESUMO

Electroactive metal-organic frameworks (MOFs) with large surface area and manipulatable structural properties show promise as a new type of signal probe for electrochemical biosensing application. In this work, an electroactive Ni-MOF, assembled by the redox-active ligands 4,4',4″-Tricarboxytriphenylamine (H3TCA), a triphenylamine derivatives, as the electroactive source and magnetic ordered Ni4O4 clusters as electronic transport nodes, is first designed and applied for electrochemical aptasensing of thrombin (Tb). The designed Ni-MOF probe realizes a stable and sensitive electrochemical signal output based on simple sandwich-type aptasensing because the high-content TCA active sites and good magnetic ordered intermediate of Ni4O4 clusters are periodically arranged in well-defined porous structure of the MOF. The Ni-MOF probe assembled by redox-active ligand presents the high stability and can be directly applied in electrochemical aptasensor, avoiding any post-modification and the addition of redox mediators. As a result, the constructed electrochemical aptasensor shows a wide linear relationship for Tb from 0.05 pM to 50 nM and a detection limit of 0.016 pM (S/N = 3). Furthermore, the proposed aptasensor is successfully applied to analysis of target Tb in real serum sample with satisfactory results. The present work indicates that fabricating a redox-active organic molecule in functionalized MOFs offer a feasible strategy to design high-stable electroactive MOFs for construction of electrochemical biosensors with simplicity, high selectivity and sensitivity.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Indicadores e Reagentes/química , Estruturas Metalorgânicas/química , Trombina/análise , Compostos de Anilina/síntese química , Compostos de Anilina/química , Ouro/química , Humanos , Ligantes , Limite de Detecção , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/síntese química , Estrutura Molecular , Níquel/química , Oxirredução
11.
Eur J Med Chem ; 163: 367-380, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30530173

RESUMO

Third-generation epidermal growth factor receptor (EGFR)L858R/T790M inhibitors are still the main drugs for the treatment of advanced non-small cell lung cancer (NSCLC), and these drugs have achieved remarkable clinical efficacy. However, there are still many patients suffering from drug-resistant mutations and drug side effects caused by NSCLC. In this study, guided by the molecular simulation, we applied a structure-based drug design strategy (SBDD) and optimized the structure to obtain a series of potent and selective EGFRL858R/T790M inhibitors. The most potent compound 18e demonstrated excellent kinase inhibitory activity and selectivity for EGFRL858R/T790M double mutants and the IC50 value reached nanomolar level. The selectivity of 18e against wild-type EGFR was near to 200-fold. In addition, compound 18e also inhibited H1975 cells proliferation at G2/M phase and induced apoptosis at a concentration of 0.25 µM, which makes it more valuable for potential lung cancer research.


Assuntos
Acrilamidas/síntese química , Compostos de Anilina/síntese química , Desenho de Drogas , Acrilamidas/química , Acrilamidas/farmacologia , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Receptores ErbB/antagonistas & inibidores , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Relação Estrutura-Atividade
12.
J Enzyme Inhib Med Chem ; 34(1): 124-133, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30422010

RESUMO

HGF/c-Met signalling pathway plays an important role in the development of cancers. A series of 6,7-dimethoxy-4-anilinoquinolines possessing benzimidazole moiety were synthesised and identified as potent inhibitors of the tyrosine kinase c-Met. Their in vitro biological activities against three cancer cell lines (A549, MCF-7, and MKN-45) were also evaluated. Most of these compounds exhibited moderate to remarkable potency. Among them, compound 12n showed the most potent inhibitory activity against c-Met with IC50 value of 0.030 ± 0.008 µM and it also showed excellent anticancer activity against the tested cancer cell lines at low micromolar concentration. Molecular docking verified the results and revealed the possible binding mode of the most promising compound 12n into the ATP-binding site of c-Met kinase.


Assuntos
Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Quinolinas/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
Int J Biol Macromol ; 126: 1112-1115, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30584931

RESUMO

3,6-Di-O-hexanoyl-N-[4-(N,N-diphenylamino)-1-phenyl] thiocarbamoyl chitosan was prepared from 3,6-di-O-hexanoyl chitosan isothiocyanate in a 78% yield, and spin-coated films of the chitosan derivative and tris(2-phenylpyridine)iridium (Ir(ppy)3) were fabricated. Ultraviolet-visible absorption spectra and photoluminescence spectra of the films indicated efficient Förster energy transfer from the chitosan derivative to the Ir(ppy)3. An electroluminescent device using both compounds emitted green luminescence when voltage was applied. The results suggested that the regio-selectively substituted chitosan derivative could be used as a scaffold in the emitting layer of organic light emitting diode.


Assuntos
Compostos de Anilina/química , Quitosana/química , Eletricidade , Fenômenos Ópticos , Compostos de Anilina/síntese química , Luminescência , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
14.
J Agric Food Chem ; 66(34): 8957-8965, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30092640

RESUMO

Inspired by established succinate dehydrogenase inhibitors (SDHIs), our continuing efforts toward the discovery of chiral antifungal amides turned to the optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis enabled the identification of promising antifungal categories. Fine tuning of the substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and 2l) as antifungal candidates, with EC50 values lower than 5 mg/L. The first investigation of chiral amides of acyclic acids as SDHIs was conducted, and compound 2d was selected as a promising candidate against Botrytis cinerea, with a preventative efficacy of up to 93.9% at 50 mg/L, which is better than that of boscalid. The different binding models between compounds with different configurations were simulated for compound 2d and its diastereoisomers. The benefits of synthetic accessibility and cost-effectiveness highlight the practical potential for compound 2d as a good alternative to known SDHI fungicides.


Assuntos
Amidas/química , Compostos de Anilina/síntese química , Compostos de Anilina/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Compostos de Anilina/química , Botrytis/efeitos dos fármacos , Botrytis/fisiologia , Desenho de Drogas , Fragaria/microbiologia , Fungicidas Industriais/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Relação Estrutura-Atividade
15.
Macromol Rapid Commun ; 39(18): e1800391, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30073723

RESUMO

Organic dipolar molecules are an emerging class of light harvesters useful in electronic applications and have captured new urgency with the design and synthesis of new molecular structures for device testing. However, research has not evolved beyond the cyclical thin film preparation-device testing-chemical structural modification approach. Without an understanding of polymorphism, molecular photophysics at the interface or metastable morphologies that regulate charge carrier dynamics, it is not obvious a priori if a new molecular structure will produce a suitable thin film morphology for superior device performance without developing structure-function relationships that consider morphology and photophysics. Dipolar, light harvesting molecules are synthesized with a covalent, para-functionalized triphenylamine donor (D) and acceptor (A) in π-conjugated structures, D-A1 and D-A1 -A2 , that have previously achieved 9.6% power conversion efficiency in thermally evaporated organic solar cell devices with C70 . Solution processing and morphological manipulation are hypothesized to reduce ultrafast radiative charge recombination, unique to dipolar structures, that prevents full charge separation to the fullerene. The photophysics of the D-A interface using femtosecond transient absorption spectroscopy is explained, and microscopy data reveal a newly discovered, supramolecular amorphous polymer metastable state presented as a transient absorption assisted strategy for photofunctional polymorph design.


Assuntos
Compostos de Anilina/síntese química , Luz , Polímeros/síntese química , Compostos de Anilina/química , Estrutura Molecular , Polímeros/química , Espectrofotometria Ultravioleta
16.
Chem Biodivers ; 15(10): e1800215, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30027551

RESUMO

A cobalt(III) complex, [Co(L)2 ](ClO4 )3 (1), in which the ligand L was N,N-diethyl-4-(2,2':6',2''-terpyridin-4'-yl)aniline (L), was synthesized and fully characterized. This new cobalt(III) complex 1 exhibited selective cytotoxicity against HeLa, T-24, A549, MGC80-3, HepG2, and SK-OV-3 cells with IC50 values in the micromolar range (0.52 - 4.33 µm), and it exhibited low cytotoxicity against normal HL-7702 cells. The complex 1 was the most potent against the T-24 cells. It was found that 1 could cause the cell cycle arrest in G1 phase, and it exerted its antitumor activity mainly via disruption of mitochondrial function.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Cobalto/química , Cobalto/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
17.
Eur J Med Chem ; 155: 782-796, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30047410

RESUMO

Epidermal growth factor receptor (EGFR) signaling pathway has been previously investigated for its significant role in the progression of different types of malignant tumors, where development of small molecules targeting EGFR is well known strategy for design of antitumor agents. Herein, we report the design and synthesis of two series of 6-(2-substitutedacetamido)-4-anilinoquinazolines (6a-x and 13a-d) as EGFR inhibitors. All the newly synthesized quinazoline derivatives were in vitro evaluated for their anti-proliferative activity towards MCF-7 (Breast Cancer) and HepG2 (Hepatocellular carcinoma) cell lines. In particular, compound 6n showed significant inhibitory activity against MCF-7 and HepG2 cell lines (IC50 = 3 and 16 µM, respectively), compared to that of Erlotinib (IC50 = 20 and 25 µM, respectively). Western blotting of 6n at MCF-7 cell line revealed the dual inhibitory activity of 6n towards diminishing the phosphorylated levels for EGFR and ERK. Also, ELISA assay confirmed the anti-EGFR activity of compound 6n (IC50 = 0.037 µM). Finally, a molecular docking study showed the potential binding mode of 6n within the ATP catalytic binding site of EGFR, exhibiting similar binding mode to EGFR inhibitor Erlotinib.


Assuntos
Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Receptores ErbB/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/biossíntese , Receptores ErbB/metabolismo , Células Hep G2 , Humanos , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química
18.
J Org Chem ; 83(10): 5844-5850, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29737848

RESUMO

3,5-Dimethylpyrazole was employed as a monodentate directing group for palladium-catalyzed ortho-sp2 C-H arylation with aryl iodides. The reaction shows good functional group tolerance and outstanding selectivity for mono- ortho-arylation. Ozonolysis of ortho-arylated arylpyrazoles gave acylated biphenylamines that were further arylated to afford unsymmetrically substituted 2,6-diarylacetanilides.


Assuntos
Compostos de Anilina/síntese química , Compostos Organometálicos/química , Paládio/química , Compostos de Anilina/química , Catálise , Estrutura Molecular , Ozônio/química
19.
Bioorg Med Chem Lett ; 28(6): 1143-1148, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29486966

RESUMO

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2-18F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (18F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/µmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of 18F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients.


Assuntos
Compostos de Anilina/farmacologia , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/farmacologia , Tomografia por Emissão de Pósitrons , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Relação Dose-Resposta a Droga , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/síntese química , Cloridrato de Erlotinib/química , Radioisótopos de Flúor , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade
20.
J Enzyme Inhib Med Chem ; 33(1): 615-628, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29536768

RESUMO

A practical and transition metal-free one-pot domino synthesis of diversified (1,3,4-oxadiazol-2-yl)anilines has been developed employing isatins and hydrazides as the starting materials, in the presence of molecular iodine. The prominent feature of this domino process involves consecutive condensation, hydrolytic ring cleavage, and an intramolecular decarboxylation, in a one-pot process that leads to the oxidative formation of a C-O bond. Fluorescence properties of some of the representative molecules obtained in this way were studied. The synthesised 2-(1,3,4-oxadiazolo-2-yl)aniline-benzene sulphonamides (8a-o) were screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity. Most of the compounds exhibited low micromolar to nanomolar activity against human (h) isoforms hCA I, hCA II, hCA IV, and XII, with some compounds displaying selective CA inhibitory activity towards hCA II with KIs of 6.4-17.6 nM.


Assuntos
Compostos de Anilina/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Iodo/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Descarboxilação , Relação Dose-Resposta a Droga , Humanos , Iodo/química , Estrutura Molecular , Relação Estrutura-Atividade
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