Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ACS Appl Mater Interfaces ; 12(1): 1322-1329, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31840977

RESUMO

Compared with traditional metal-oxide lithium-ion battery (LIB) cathodes, nanocarbon-based cathode materials have received much attention for potential application in LIBs because of their superior power density and long-term cyclability. However, their lithium-ion storage capacity needs further improvement for practical applications, and the trade-off between capacity and conductivity, when oxygen functional groups as lithium-ion storage sites are introduced to the nanocarbon materials, needs to be addressed. Here, we report a sequential oxidation-reduction process for the synthesis of single-walled carbon nanotubes (SWCNTs) for LIB cathodes with fast charging, long-term cyclability, and high gravimetric capacity. A LIB cathode based on highly exfoliated (dbundle < 10 nm) and oxygen-functionalized single-walled carbon nanotubes is obtained via the modified Brodie's method using fuming nitric acid and a mild oxidant (B-SWCNTs). Post treatment including horn sonication and hydrogen thermal reduction developed surface defects and removed the unnecessary C-O groups, resulting in an increase in the Li-ion storage capacity. The B-SWCNTs exhibit a high reversible gravimetric capacity of 344 mA h g-1 at 0.1 A g-1 without noticeable capacity fading after 1000 cycles. Furthermore, it delivers a high gravimetric energy density of 797 W h kgelectrode-1 at a low gravimetric power density of 300 W kgelectrode-1 and retains its high gravimetric energy density of ∼100 W h kgelectrode-1 at a high gravimetric power of 105 W kgelectrode-1. These results suggest that the highly exfoliated, oxygen-functionalized single-walled carbon nanotubes can be applied to LIBs designed for high-rate operations and long cycling.

2.
Sci Rep ; 9(1): 2322, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787333

RESUMO

The demand for easy-to-use portable electric devices that are combined with essential items in everyday life, such as apparel, has increased. Hence, significant research has been conducted into the development of wearable technology by fabrication of electronic devices with a textile structure based on fiber or fabric. However, the challenge to develop a fabrication method for wearable devices based on weaving or sewing technology still remains. In this study, we have proposed and fabricated a 3-D textile with two electrodes and one spacer in a single sheet of fabric, utilizing a commercial weaving machine. The two electrodes fulfil the role of electron transfer and the spacer between the electrodes circulates electrons and prevents electrical shorting. Hence, the 3-D textile could be applied to a wide range of electrochemical devices. In addition, it is possible to control the textile structure, size and quantity and change the electrode or spacer materials by replacing the thread. We applied the 3-D textile to dye-sensitized solar cells (DSSCs) which has distinctive advantages such as low manufacturing cost, esthetic appearance for interior or exterior application and high power output under relatively weak light illuminations. The 3-D textile DSSCs were fabricated through a continuous process, from manufacturing to encapsulation, using a non-volatile electrolyte and demonstrated a specific power of 1.7% (1 sun, 1.5 A.M.). The 3-D textile DSSCs were electrically connected in parallel and series by twisting, stainless steel wires, which were used as the weft, and a light-emitting diode lamp was turned on using 3-D textile DSSCs connected in series. This study represents the first stage in the development and application of wearable textile devices.

3.
Sci Rep ; 8(1): 17649, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504859

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

5.
Bioorg Med Chem ; 26(21): 5596-5611, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30385226

RESUMO

Two new series of 5-subtituted and 5,6-disubstituted pyrrolo[2,3-d]pyrimidine octamides (4a-o and 6a-g) and their corresponding free amines 5a-m and 7a-g have been synthesized and biologically evaluated for their antiproliferative activity against three human cancer cell lines. The 5,6-disubstituted octamides 6d-g as well as the amine derivative 7b have shown the best anticancer activity with single digit micromolar GI50 values over the tested cancer cells, and low cytotoxic effects (GI50 > 10.0 µM) against HFF-1 normal cell. A structure activity relationship (SAR) study has been established and disclosed that terminal octamide moiety at C2 as well as disubstitution with fluorobenzyl piperazines at C5 and C6 of pyrrolo[2,3-d]pyrimidine are the key structural features prerequisite for best antiproliferative activity. Moreover, the most active member 6f was tested for its antiproliferative activity over a panel of 60 cancer cell lines at NCI, and exhibited distinct broad spectrum anticancer activity with submicromolar GI50 and TGI values over multiple cancer cells. Kinase profile of compound 6f over 53 oncogenic kinases at 10 µM concentration showed its highly selective inhibitory activity towards FGFR4, Tie2 and TrkA kinases. The observed activity of 6f against TrkA (IC50 = 2.25 µM), FGFR4 (IC50 = 6.71 µM) and Tie2 (IC50 = 6.84 µM) was explained by molecular docking study, which also proposed that 6f may be a type III kinase inhibitor, binding to an allosteric site rather than kinase hinge region. Overall, compound 6f may serve as a promising anticancer lead compound that could be further optimized for development of potent anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinas/farmacocinética , Pirróis/síntese química , Pirróis/química , Pirróis/farmacocinética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/química , Receptor TIE-2/antagonistas & inibidores , Receptor TIE-2/química , Receptor trkA/antagonistas & inibidores , Receptor trkA/química
6.
Chem Biol Drug Des ; 92(2): 1555-1566, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29718569

RESUMO

Overexpression of GRP78 in a variety of cancers such as glioblastoma, leukemia, lung, prostate, breast, gastric, and colon makes it a prime target for anticancer drug development. Present study reports GRP78-based design of novel anticancer agents using in-silico methods. As a first step toward the work, the interactions between GRP78 and 15 known ligands were modeled by docking simulation. The docked complex, GRP78-13, superior to other compounds with respect to its experimental activity and energy descriptors, was deduced into a structure-based pharmacophore. This hypothesis was applied as a screening filter to Asinex and Chemdiv databases. Finally, 23 hits were tested in vitro. Among these, VH1019 and VH1011 induced a concentration-dependent strong broad antiproliferative effect in glioma (U87-MG), breast cancer (MCF-7), and prostate cancer (DU-145) cell lines as compared to nontumorigenic control, neonatal foreskin fibroblast (HFF-1). These compounds showed preferential growth inhibition of cancer cells over normal cells. The acetohydrazide derivative VH1019 was identified as a potential new chemotype for GRP78 inhibitors with an IC50 of 12.7 µM in MCF-7.


Assuntos
Antineoplásicos/química , Proteínas de Choque Térmico/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Proteínas de Choque Térmico/metabolismo , Humanos , Ligantes , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Relação Quantitativa Estrutura-Atividade , Teoria Quântica , Termodinâmica
7.
ACS Omega ; 3(1): 698-705, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31457925

RESUMO

The dye-sensitized solar cell (DSSC) is a potential alternative to the widely used Si-based solar cell, with several advantages including higher energy conversion efficiency under weak and indirect illumination conditions, and the possibility of practical application in urban life due to their exterior characteristics. However, despite these advantages, the energy conversion efficiency of DSSCs has remained low at ∼10%. To improve the efficiency of DSSCs, research has been done on modifying the materials used in DSSC component parts, such as the photoanode, electrolyte, and counter electrode. Another approach is to modify the photoanode to increase the diffusion coefficient, reduce the recombination rate, and enhance the light behavior. One of the most popular methods for improving the efficiency of DSSCs is by trapping and dispersing the incident light using a scattering layer. Use of a scattering layer has shown various and interesting results, depending on the application, but it is currently used only in a simple form and there has been no deep research on the further potential of the scattering layer. In this study, the scattering center was introduced to maximize the effect of scattering. Light distribution near the scattering center, within or on the photoanode, was investigated using finite differential time domain (FDTD) numerical methods. Based on the FDTD analysis, an optimized, dome-shaped three-dimensional modified structure of a transparent photoanode with minimized scattering centers was introduced and indicated the possibility of modifying the photon distribution in the photoanode to enhance the performance of DSSCs. In addition to using the scattering center, we have introduced the structure of the dome-shaped three-dimensional structure to utilize the light distribution within the photoanode. This novel three-dimensional transparent photoanode and scattering center design increased the energy conversion efficiency of DSSCs from 6.3 to 7.2%. These results provide a foundation for investigating the role of the scattering center via further in-depth research. This new three-dimensional photoanode design provides a means to overcome the previous limitations on DSSC performance.

8.
Sci Rep ; 7(1): 15027, 2017 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-29118408

RESUMO

Dye sensitize solar cells (DSSCs) have been considered as the promising alternatives silicon based solar cell with their characteristics including high efficiency under weak illumination and insensitive power output to incident angle. Therefore, many researches have been studied to improve the energy conversion efficiency of DSSCs. However the efficiency of DSSCs are still trapped at the around 10%. In this study, micro-scale hexagonal shape patterned photoanode have proposed to modify light distribution of photon. In the patterned electrode, the appearance efficiency have been obtained from 7.1% to 7.8% considered active area and the efficiency of 12.7% have been obtained based on the photoanode area. Enhancing diffusion of electrons and modification of photon distribution utilizing the morphology of the electrode are major factors to improving the performance of patterned electrode. Also, finite element method analyses of photon distributions were conducted to estimate morphological effect that influence on the photon distribution and current density. From our proposed study, it is expecting that patterned electrode is one of the solution to overcome the stagnant efficiency and one of the optimized geometry of electrode to modify photon distribution. Process of inter-patterning in photoanode has been minimized.

9.
Sci Rep ; 7(1): 4931, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28694467

RESUMO

Most synthetic processes of metallic nanostructures were assisted by organic/inorganic or polymeric materials to control their shapes to one-dimension or two-dimension. However, these additives have to be removed after synthesis of metal nanostructures for applications. Here we report a straightforward method for the low-temperature and additive-free synthesis of nanobelt-like silver nanostructures templated by nanocarbon (NC) materials via bio-inspired shape control by introducing supramolecular 2-ureido-4[1H]pyrimidinone (UPy) groups into the NC surface. The growth of the Ag nanobelt structure was found to be induced by these UPy groups through observation of the selective formation of Ag nanobelts on UPy-modified carbon nanotubes and graphene surfaces. The synthesized NC/Ag nanobelt hybrid materials were subsequently used to fabricate the highly conductive fibres (>1000S/cm) that can function as a conformable electrode and highly tolerant strain sensor, as well as a highly conductive and robust paper (>10000S/cm after thermal treatment).

10.
ACS Appl Mater Interfaces ; 9(8): 7780-7786, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28155268

RESUMO

Directly printed superhydrophobic surfaces containing conducting nanomaterials can be used for a wide range of applications in terms of nonwetting, anisotropic wetting, and electrical conductivity. Here, we demonstrated that direct-printable and flexible superhydrophobic surfaces were fabricated on flexible substrates via with an ultrafacile and scalable screen printing with carbon nanotube (CNT)-based conducting pastes. A polydimethylsiloxane (PDMS)-polyethylene glycol (PEG) copolymer was used as an additive for conducting pastes to realize the printability of the conducting paste as well as the hydrophobicity of the printed surface. The screen-printed conducting surfaces showed a high water contact angle (WCA) (>150°) and low contact angle hysteresis (WCA < 5°) at 25 wt % PDMS-PEG copolymer in the paste, and they have an electrical conductivity of over 1000 S m-1. Patterned superhydrophobic surfaces also showed sticky superhydrophobic characteristics and were used to transport water droplets. Moreover, fabricated films on metal meshes were used for an oil/water separation filter, and liquid evaporation behavior was investigated on the superhydrophobic and conductive thin-film heaters by applying direct current voltage to the film.

11.
Chem Biol Drug Des ; 89(1): 98-113, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27496071

RESUMO

A series of new 2-anilinoquinolines 6a-o possessing the substantial N-methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogs. The antiproliferative activities of the target compounds were preliminarily appraised against a panel of three human cancer cell lines (MCF-7, SK-BR3, and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10 µM concentration. Interestingly, compounds 6c, 6d, 6j, 6k, and 6l showed promising selective anticancer activities (growth inhibition >80%) toward certain cancer cells at 10 µM testing dose. Compounds 6d and 6j were advanced to five-dose testing mode to determine their GI50 values and compared with our previously reported ureidoquinoline B and sorafenib as reference compounds. The 4-chloro-3-trifluoromethylaniline derivative 6j manifested superior potency than both compound B and sorafenib over eleven and eight cell lines, respectively. It showed GI50 values of 0.36, 0.66, 0.68, and 0.60 µM against the breast MDA-MB-468, renal A498, and melanoma SK-MEL-5 and UACC-62 cell lines, respectively. Moreover, both 6d and 6j exerted low cytotoxic effects against HFF-1 normal cell line. Furthermore, compounds 6d and 6j were tested against both B-RafV600E and C-Raf kinases and displayed modest inhibitory activities, which were justified by molecular docking study. Compound 6j could serve as a promising candidate for further development of potent anticancer chemotherapeutics.


Assuntos
Amidas/química , Proliferação de Células/efeitos dos fármacos , Quinolinas/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos , Simulação de Acoplamento Molecular , Espectroscopia de Prótons por Ressonância Magnética , Quinolinas/síntese química , Quinolinas/farmacologia
12.
Bioorg Med Chem Lett ; 27(2): 237-241, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27914802

RESUMO

A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50 of 36nM and showed a submicromolar mean GI50 value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Pirimidinas/farmacologia , Pirróis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Relação Estrutura-Atividade
13.
Sci Rep ; 6: 34249, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27708359

RESUMO

Textile-structured solar cells are frequently discussed in the literature due to their prospective applications in wearable devices and in building integrated solar cells that utilize their flexibility, mechanical robustness, and aesthetic appearance, but the current approaches for textile-based solar cells-including the preparation of fibre-type solar cells woven into textiles-face several difficulties from high friction and tension during the weaving process. This study proposes a new structural concept and fabrication process for monolithic-structured textile-based dye-sensitized solar cells that are fabricated by a process similar to the cloth-making process, including the preparation of wires and yarns that are woven for use in textiles, printed, dyed, and packaged. The fabricated single-layered textile-based dye-sensitized solar cells successfully act as solar cells in our study, even under bending conditions. By controlling the inter-weft spacing and the number of Ti wires for the photoelectrode conductor, we have found that the performance of this type of dye-sensitized solar cell was notably affected by the spacing between photoelectrodes and counter-electrodes, the exposed areas of Ti wires to photoelectrodes, and photoelectrodes' surface morphology. We believe that this study provides a process and concept for improved textile-based solar cells that can form the basis for further research.

14.
J Comput Aided Mol Des ; 30(8): 625-37, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27600555

RESUMO

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor, mediating inflammation and pain signaling in neurons, thus it is considered to be a potential therapeutic target for inflammatory diseases. In this study, we performed a ligand-based virtual screening of 1.6 million compounds by employing a common-feature pharmacophore model and two-dimensional similarity search to identify a new PAR2 antagonist. The common-feature pharmacophore model was established based on the biological screening results of our in-house library. The initial virtual screening yielded a total number of 47 hits, and additional biological activity tests including PAR2 antagonism and anti-inflammatory effects resulted in a promising candidate, compound 43, which demonstrated an IC50 value of 8.22 µM against PAR2. In next step, a PAR2 homology model was constructed using the crystal structure of the PAR1 as a template to explore the binding mode of the identified ligands. A molecular docking method was optimized by comparing the binding modes of a known PAR2 agonist GB110 and antagonist GB83, and applied to predict the binding mode of our hit compound 43. In-depth docking analyses revealed that the hydrophobic interaction with Phe243(5.39) is crucial for PAR2 ligands to exert antagonistic activity. MD simulation results supported the predicted docking poses that PAR2 antagonist blocked a conformational rearrangement of Na(+) allosteric site in contrast to PAR2 agonist that showed Na(+) relocation upon GPCR activation. In conclusion, we identified new a PAR2 antagonist together with its binding mode, which provides useful insights for the design and development of PAR2 ligands.


Assuntos
Receptor PAR-2/antagonistas & inibidores , Receptor PAR-2/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Sequência de Aminoácidos , Animais , Células CHO , Cricetulus , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptor PAR-2/química , Alinhamento de Sequência
15.
Eur J Med Chem ; 115: 201-16, 2016 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-27017549

RESUMO

A new series of benzothiazole amide and urea derivatives tethered with the privileged pyridylamide moiety by ether linkage at the 6-position of benzothiazole (22 final compounds) has been designed and synthesized as potent anticancer sorafenib analogs. A selected group of twelve derivatives was appraised for its antiproliferative activity over a panel of 60 human cancer cell lines at a single dose concentration of 10 µM at National Cancer Institute (NCI, USA). Compounds 4b, 5a, 5b and 5d exhibited promising growth inhibitions and thus were further tested in advanced 5-dose testing assay to determine their GI50 values. The cellular based assay results revealed that 3,5-bis-trifluoromethylphenyl (5b) urea member is the best derivative with superior potency and efficacy compared to sorafenib as well as notable extended spectrum activity covering 57 human cancer cell lines. Kinase screening of compound 5b showed its kinase inhibitory effect against both B-Raf(V600E) and C-Raf. Moreover, the most potent derivatives in cells were investigated for their RAF inhibitory activities, and the results were rationalized with the molecular docking study. Profiling of CYP450 and hERG channel inhibitory effects for the active compounds revealed their low possibilities to exhibit undesirable drug-drug interactions and cardiac side effects.


Assuntos
Antineoplásicos/farmacologia , Desenho de Drogas , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzotiazóis/síntese química , Benzotiazóis/química , Benzotiazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química , Ureia/farmacologia
16.
Chem Biol Drug Des ; 87(2): 239-56, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26343933

RESUMO

Metabotropic glutamate receptor 1 (mGluR1) is considered as an attractive drug target for neuropathic pain treatments. The hierarchical virtual screening approach for identifying novel scaffolds of mGluR1 allosteric modulators was performed using a homology model built with the dopamine D3 crystal structure as template. The mGluR1 mutagenesis data, conserved amino acid sequences across class A and class C GPCRs, and previously reported multiple sequence alignments of class C GPCRs to the rhodopsin template, were employed for the sequence alignment to overcome difficulties of model generation with low sequence identity of mGluR1 and dopamine D3. The structures refined by molecular dynamics simulations were employed for docking of Asinex commercial libraries after hierarchical virtual screening with pharmacophore and naïve Bayesian models. Five of 35 compounds experimentally evaluated using a calcium mobilization assay exhibited micromolar activities (IC50) with chemotype novelty that demonstrated the validity of our methods. A hierarchical structure and ligand-based virtual screening approach with homology model of class C GPCR based on dopamine D3 class A GPCR structure was successfully performed and applied to discover novel negative mGluR1 allosteric modulators.


Assuntos
Receptores de Glutamato Metabotrópico/química , Regulação Alostérica , Sítio Alostérico , Sequência de Aminoácidos , Área Sob a Curva , Teorema de Bayes , Desenho de Drogas , Humanos , Concentração Inibidora 50 , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Curva ROC , Receptores de Dopamina D3/química , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Alinhamento de Sequência , Máquina de Vetores de Suporte
17.
Eur J Med Chem ; 101: 754-68, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26218653

RESUMO

New 2-amido and ureido quinoline derivatives substituted with 2-N-methylamido-pyridin-4-yloxy group at the 5-position of quinoline (18 final compounds) have been designed and synthesized as anticancer sorafenib congeners. Among the synthesized derivatives, fourteen compounds were selected for evaluation of their antiproliferative activity over a panel of 60 cancer cell lines at a single dose concentration of 10 µM at National Cancer Institute (NCI, USA). Four compounds, 9b-d and 9f showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC50 values. The data revealed that 2,4-difluorophenyl (9b) and 4-chloro-3-trifluoromethylphenyl (9d) urea compounds are the most active derivatives with significant efficacies and superior potencies than sorafenib in 36 and 12 cancer cell lines, respectively, belonging particularly to renal carcinoma cell (RCC), ovarian, and non small cell lung cancer (NSCL). Compound 9b and 9d were found to be six and two times more potent than sorafenib against A498 RCC line, with IC50 values of 0.42 µM and 1.36 µM, respectively. Accordingly, compound 9d was screened over a panel of 41 oncogenic kinases at a single dose concentration of 10 µM to profile its kinase inhibitory activity. Interestingly, the compound showed highly selective inhibitory activities ( 81.8% and 96.3%) against BRAF(V600E) and C-RAF kinases with IC50 values of 316 nM and 61 nM, respectively. In addition, molecular docking, cell cycle analysis, compliance to Lipinski's rule of five, and in silico toxicity assessment have been reported.


Assuntos
Antineoplásicos/farmacologia , Desenho de Drogas , Ácidos Picolínicos/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/metabolismo , Quinolinas/farmacologia , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade
18.
Sci Rep ; 5: 11022, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-26087134

RESUMO

Increasing demands for wearable energy sources and highly flexible, lightweight photovoltaic devices have stimulated the development of textile-structured solar cells. However, the former approach of wire-type solar cell fabrication, followed by weaving of these devices, has had limited success, due to device failure caused by high friction forces and tension forces during the weaving process. To overcome this limitation, we present a new approach for textile solar cell fabrication, in which dye-sensitized solar cell (DSSC) electrodes are incorporated into the textile during the weaving process, using the textile warp as a spacer to maintain the DSSC structure. Porous, dye-loaded TiO2-coated holed metal ribbon and Pt nanoparticle-loaded carbon yarn were used as the photoanode and counterelectrode, respectively. The highly flexible textile-based solar cell was fabricated using a common weaving process with a loom. The inserted DSSCs in the textile demonstrated an energy conversion efficiency of 2.63% (at 1 sun, 1.5 A.M.). Our results revealed that additional performance enhancement was possible by considering other electrode materials and textile structures, as well as where and how the DSSC electrodes are inserted. In addition, we demonstrated that the inserted DSSCs could be electrically connected using a parallel configuration.

19.
Eur J Med Chem ; 97: 245-58, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-25984841

RESUMO

Metabotropic glutamate receptor 1 (mGluR1) has been a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, we designed and synthesized a library of compounds with tetrahydrothieno[2,3-c]pyridine scaffold. Among these compounds, compound 9b and 10b showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 9b exhibited a favorable pharmacokinetic profile in rats. We believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Modelos Animais de Doenças , Descoberta de Drogas , Neuralgia/tratamento farmacológico , Nitrilos/química , Nitrilos/farmacologia , Piridinas/química , Piridinas/farmacologia , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/farmacocinética , Animais , Células Cultivadas , Células HEK293 , Humanos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Nitrilos/administração & dosagem , Nitrilos/farmacocinética , Piridinas/administração & dosagem , Piridinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/metabolismo , Relação Estrutura-Atividade , Distribuição Tecidual
20.
ACS Appl Mater Interfaces ; 7(20): 10863-71, 2015 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-25945810

RESUMO

Electrocatalytic materials with a porous structure have been fabricated on glass substrates, via high-temperature fabrication, for application as alternatives to platinum in dye-sensitized solar cells (DSCs). Efficient, nonporous, nanometer-thick electrocatalytic layers based on graphene oxide (GO) nanosheets were prepared on plastic substrates using electrochemical control at low temperatures of ≤100 °C. Single-layer, oxygen-rich GO nanosheets prepared on indium tin oxide (ITO) substrates were electrochemically deoxygenated in acidic medium within a narrow scan range in order to obtain marginally reduced GO at minimum expense of the oxygen groups. The resulting electrochemically reduced GO (E-RGO) had a high density of residual alcohol groups with high electrocatalytic activity toward the positively charged cobalt-complex redox mediators used in DSCs. The ultrathin, alcohol-rich E-RGO layer on ITO-coated poly(ethylene terephthalate) was successfully applied as a lightweight, low-temperature counter electrode with an extremely high optical transmittance of ∼97.7% at 550 nm. A cobalt(II/III)-mediated DSC employing the highly transparent, alcohol-rich E-RGO electrode exhibited a photovoltaic power conversion efficiency of 5.07%. This is superior to that obtained with conventionally reduced GO using hydrazine (3.94%) and even similar to that obtained with platinum (5.10%). This is the first report of a highly transparent planar electrocatalytic layer based on carbonaceous materials fabricated on ITO plastics for application in DSCs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA