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1.
Nanoscale Adv ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39144160

RESUMO

In this study, bio-based carbon nanospheres (CNSs) were synthesized from lignocellulosic-rich groundnut skin (Arachis hypogaea) and tested for their practical application in nanofluids (NFs) for enhanced heat transfer. The CNSs were characterized using various techniques, including FESEM, EDS, XRD, Raman spectroscopy, zeta potential analysis, and FTIR. Thermal conductivity (TC) and viscosity measurements were conducted using transient plane source (TPS) technique with a Hot Disk thermal analyser and discovery hybrid rheometer, respectively. The nanoparticles (NPs) were dispersed in two base fluids: ethylene glycol (EG) and a 60 : 40 mixture of deionized water (DI) and EG. Optimization studies were performed by varying the stirring and measurement times to improve TC values. The results showed that when a power source of 40 mW was applied at a high concentration of nanoparticles (i.e., 0.1 wt%), there was a 91.9% increment in thermal conductivity (TC) compared to the base fluid EG. DI-EG-based nanofluids (NFs) exhibited enhancements of up to 45% compared to the base fluid DI-EG (60 : 40), with a heating power of 80 mW and concentration of 0.1 wt%. These results demonstrated significant TC improvements with NP incorporation. Further experiments were performed by varying the temperature in the range of 30-80 °C with readings taken for every 10 °C increase, which showed a direct relation with the TC values. At 80 °C, EG-based NFs showed increments of 77%, 111.49%, 139.67% and 175% at 0.01, 0.02, 0.05 and 0.1 wt% concentrations of NPs, respectively. It was also found that with the increase in the concentration of NPs, viscosity increased, whereas an increase in the temperature led to a decrease in viscosity. The CNS nanofluid exhibited a Newtonian behaviour with the nanoparticle concentration and temperature, resulting in an approximately 114% enhancement compared to the base fluid when the concentration of CNSs was 0.1 wt% at 30 °C but decreased by up to 18% when the temperature was increased to 90 °C. Using appropriate mathematical models for assessing thermophysical quantities, it was discovered that the model values and experimental values correspond reasonably well. Our method thus validates our experimental results and deepens the understanding of the mechanisms behind enhancing thermal conductivity in biomass-derived nanofluids. In summary, our work advances sustainable nanomaterial synthesis, providing a new solution for boosting thermal conductivity while maintaining environmental integrity, thereby inspiring further research and innovation in this field.

2.
Nanoscale ; 16(32): 15343-15357, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39087876

RESUMO

The exploration of 'electrostatic self-assembly' on solid surfaces has garnered significant interest across various fields. With the sophistication of gadgets, managing electromagnetic interference (EMI) from stray signals, especially in stealth applications, necessitates materials that can absorb microwaves. A promising approach involves integrating lightweight self-healing polymeric materials. This study employs electrostatic self-assembly to design a carbon nanotube structure on an interpenetrating polymer network (IPN) made of PVDF and bismaleimide (BMI)-grafted dopamine hydrochloride, enhancing mechanical integrity through well-formed IPNs. Graphene oxide (GO) is introduced before IPN formation to facilitate an 'acceptor-donor' interaction via the Diels-Alder adduct between BMI and GO, which binds with multi-walled carbon nanotubes (MWCNTs). MWCNTs, modified with PQ7 or PDDA for a positive charge, self-assemble onto the IPN-GO construct, creating a lightweight and chemically stable structure capable of absorbing electromagnetic radiation. The 21 µm thick construct exhibits enhanced microwave absorption within the X-band (8.2-12.4 GHz), with a specific shielding effectiveness of 8637 dB cm2 g-1 and a green index (gs ≈ 1.41). The construct is coated with self-healable polyetherimide (PEI) containing exchangeable disulfide bonds to address maintenance challenges, providing heat-triggered self-healing properties. These innovative structures offer solutions for 5G and IoT applications where lightweight, durable, and multifunctional properties are essential for effectively shielding electronic devices from stray signals.

3.
ACS Appl Mater Interfaces ; 16(25): 31877-31894, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38868858

RESUMO

Interfacial failure in carbon fiber-reinforced epoxy (CFRE) laminates is a prominent mode of failure, attracting significant research attention. The large surface-energy mismatch between carbon fiber (CF) and epoxy results in a weaker interface. This study presents a facile yet effective method for enhancing the interfacial adhesion between CF and epoxy with self-healable interfaces. Two variants of a designer sizing agent, poly(ether imide) (PEI), were synthesized, one without a self-healing property termed BO, and the second one by incorporating disulfide metathesis in one of its monomers that renders self-healing properties at the interface-mediated by network reconfiguration, termed BA. 0.25 wt % of CF was found to be the optimum amount of BO and BA sizing agents. The surface free energy of CF drastically increased and became quite close to the surface energy of epoxy after the deposition of both sizing agents and the higher surface roughness. The improved surface wettability, presence of functional groups, and mechanical interlocking worked in tandem to strengthen the interface. The interlaminar shear strength (ILSS) and flexural strength (FS) of CFRE laminate sized with BO consequently increased by 35% and 22% and of CFRE laminate sized with BA increased by 26% and 19%, respectively. Fractography analysis revealed outstanding bonding between epoxy and PEI-CF, indicating that matrix fracture is the predominant mode of failure. The self-healable interfaces due to the preinstalled disulfide metathesis in the sizing agent resulted in 51% self-healing efficiency in ILSS for BA-sized CFRE laminate. Interestingly, the functional properties, deicing, and EMI shielding effectiveness were not compromised by modification of the interface with this designer sizing agent. This study opens new avenues for interfacial modification to improve the mechanical properties while retaining the key functional properties of the laminates.

4.
Nanoscale ; 16(14): 6984-6998, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38445355

RESUMO

Carbon fiber-reinforced epoxy (CFRE) laminates have attracted significant attention as a structural material specifically in the aerospace industry. In recent times, various strategies have been developed to modify the carbon fiber (CF) surface as the interface between the epoxy matrix and CFs plays a pivotal role in determining the overall performance of CFRE laminates. In the present work, graphene oxide (GO) was used to tag a polyetherimide (PEI, termed BA) containing exchangeable bonds and was employed as a sizing agent to improve the interfacial adhesion between CFs and epoxy. This unique GO-tagged-BA sizing agent termed BAGO significantly enhanced the mechanical properties of CFRE laminates by promoting stronger interactions between CFs and the epoxy matrix. The successful synthesis of BAGO was verified by Fourier-transform infrared spectroscopy. Additionally, the partial reduction of GO owing to this tagging with BA was further confirmed by X-ray diffraction and Raman spectroscopy, and the thermal stability of this unique sizing agent was evaluated using thermogravimetric analysis. The amount of GO in BAGO was optimized as 0.25 wt% of BA termed 0.25-BAGO. The 0.25-BAGO sizing agent resulted in a significant increase in surface roughness, from 15 nm to 140 nm, and surface energy, from 13.2 to 34.7 mN m-1 of CF. The laminates prepared from 0.25-BAGO exhibited a remarkable 40% increase in flexural strength (FS) and a 35% increase in interlaminar shear strength (ILSS) due to interfacial strengthening between epoxy and CFs. In addition, these laminates exhibited a self-healing efficiency of 51% in ILSS due to the presence of dynamic disulfide bonds in BAGO. Interestingly, the laminates with 0.25-BAGO exhibited enhanced Joule heating and enhanced deicing, though the EMI shielding efficiency slightly declined.

5.
Bioengineering (Basel) ; 10(10)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37892879

RESUMO

Temperature downshifts are the gold standard when setting up control strategies for mammalian cell culture processes. These shifts are performed to prolong production phases and attain heightened levels of productivity. For the development of biosimilars, however, the bottleneck is in achieving a prespecified product quality. In a late-stage development project, we investigated the impact of temperature shifts and other process parameters with the aim of optimizing the glycosylation profile of a monoclonal antibody (mAb). We applied a design of experiments approach on a 3 L scale. The optimal glycosylation profile was achieved when performing a temperature upshift from 35.8 °C to 37 °C. Total afucosylated glycan (TAF) decreased by 1.2%, and galactosylated glycan species (GAL) increased by up to 4.5%. The optimized control strategy was then successfully taken to the manufacturing scale (1000 L). By testing two sets of set points at the manufacturing scale, we demonstrated that the statistical models predicting TAF and GAL trained with small-scale data are representative of the manufacturing scale. We hope this study encourages researchers to widen the screening ranges in process development and investigate whether temperature upshifts are also beneficial for other mAbs.

6.
ACS Nano ; 17(8): 7272-7284, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37036338

RESUMO

Self-assembled graphene oxide lyotropic liquid crystal (GO LLC) structures are mostly formed in aqueous medium; however, most GO derivatives are water insoluble, so processing GO LLCs in water poses a practical limitation. The use of polar aprotic solvent (like dimethyl sulfoxide) for the formation of GO LLC structures would be interesting, because it would allow incorporating additives, like photoinitiators or cross-linkers, or blending with polymers that are insoluble in water, which hence would expand its scope. The well-balanced electrostatic interaction between DMSO and GO can promote and stabilize the GO nanosheets' alignment even at lower concentrations. With this in mind, herein we report mechanically robust, chlorine-tolerant, self-assembled nanostructured GO membranes for precise molecular sieving. Small-angle X-ray scattering and polarized optical microscopy confirmed the alignment of the modified GO nanosheets in polar aprotic solvent, and the LLC structure was effectively preserved even after cross-linking under UV light. We found that the modified GO membranes exhibited considerably improved salt rejection for monovalent ions (99%) and water flux (120 LMH) as compared to the shear-aligned GO membrane, which is well supported by forward osmosis simulation studies. Additionally, our simulation studies indicated that water molecules traveled a longer path while permeating through the GO membrane compared to the GO LLC membrane. Consequently, salt ions permeate slowly across the GO LLC membrane, yielding higher salt rejection than the GO membrane. This begins to suggest strong electrostatic repulsion with the salt ions, causing higher salt rejection in the GO LLC membrane. We foresee that the ordered cross-linked GO sheets contributed to excellent mechanical stability under a high-pressure, cross-flow, chlorine environment. Overall, these membranes are easily scalable, exhibit good mechanical stability, and represent a breakthrough for the potential use of polymerized GO LLC membranes in practical water remediation applications.

7.
Nanoscale ; 15(8): 3805-3822, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36723254

RESUMO

In the era of fifth-generation networks and the Internet of Things, new classes of lightweight, ultrathin, and multifunctional electromagnetic interference (EMI) shielding materials have become inevitable prerequisites for the protection of electronics from stray electromagnetic signals. In the present study, for the first time, we have designed a unique nanohybrid composed of a copper-based polyoxometalate (Cu-POM)-immobilized carbon nanotube construct, having a micron (∼100 µm)-level thickness, through a facile vacuum-assisted filtration technique. In this course of study, a total of four Cu-POMs, two from each category of Keggin and Anderson bearing opposite charges, i.e., positive and negative, have been rationally selected to investigate the effects of the host-guest electrostatic interaction between CNT and POMs in the EMI shielding performance. This approach of the host-guest electrostatic assembly between Cu-based polyanionic oxo clusters and counter-charged CNTs in the construct synergistically enhances the EMI shielding performance compared to the individual components dominated by 90% absorption in the X-band (8.2-12.4 GHz) frequency regime. Further, mutable EMI SE can be achieved by tuning the concentration of POMs and CNTs with different weight ratios. Such Cu-POM-immobilized CNT constructs demonstrating excellent shielding (∼45 dB) are not amenable via any other conventional routes, including flakes and dispersion.

8.
Mater Sci Eng C Mater Biol Appl ; 120: 111697, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545856

RESUMO

In the present study, a magnetic nanocomposite (magnetite Fe3O4 and hematite Fe2O3) has been successfully synthesized by the sol-gel method and coated with polyvinyl alcohol (PVA) followed by conjugation of anti-diabetic drug metformin. Detailed structural and microstructural characterization of the nanocomposite (NP) and drug conjugated nanocomposite (NP-DC) are analyzed by the Rietveld refinement of respective XRD patterns, FTIR analysis, UV-Vis spectroscopy, SEM and TEM results. SEM and TEM image analyses reveal the spherical morphology and average size of NP, PVA coated nanoparticles (NP-PVA) and NP-DC samples, indicating a suitable size to be a nanocarrier. The biocompatibility of NP and NP-DC was carried out in NIH/3T3 and J774A. 1 cells. The enhanced activity of the drug, when conjugated with nanocomposite, is confirmed after the treatment of both the pure drug and NP-DC sample on the 18 h fasted normoglycemic and hyperglycemic mice. The blood glucose level of the mice is effectively decreased with the same concentration of the pure drug and NP-DC sample. It proves the increased activity of the NP-DC sample, as only 5 wt% drug is present that shows the same efficiency as the pure drug. This study suggests excellent biocompatibility and cytocompatibility of NP and NP-DC besides the critical property as a hypoglycemic agent. It is the first time approach of conjugating metformin with a magnetic nanocomposite for a significant increment of its hypoglycemic activity, which is very important to reduce the side effect of metformin for its prolonged use.


Assuntos
Nanocompostos , Preparações Farmacêuticas , Animais , Hipoglicemiantes/farmacologia , Fenômenos Magnéticos , Magnetismo , Camundongos
9.
Mater Sci Eng C Mater Biol Appl ; 106: 110160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753371

RESUMO

Cu-Ag-ZnO nanocomposite (NC) has been successfully synthesized by mechanical alloying the Cu, Zn and Ag powder mixture under Ar atmosphere within 4 h of milling. The nanocomposite is then conjugated with the antifungal drug fluconazole by adding 5 wt% powdered drug to the NC and mechanical alloying the total powder mixture for one more hour. The Rietveld refinement of XRD data and FTIR spectrum analyses reveal the detailed structural and microstructural characterizations of the nanocomposite-drug conjugate (NC-DC). Presence of Cu, Ag, ZnO and drug in the 5 h milled powder are confirmed by analyzing TEM images and FESEM-EDS spectrum. Results obtained from FESEM and TEM images reveal the measure of particle size of the nanocomposite-drug conjugate and it agrees well with the crystallite size obtained from the Rietveld refinement. A significant antifungal activity of NC-DC against Candida sp. fungi has been revealed using disk agar diffusion method. Minimum inhibitory concentration (MIC) test confirms that NC-DC with only 5 wt% fluconazole produces similar antifungal activity of the pure (100 wt%) and conventional fluconazole. Thus, the conjugation of conventional drug to a nanocomposite results in enhancement of drug efficiency by a factor 20 folds. This is very important, particularly, for those antibiotics which are very effective in controlling several epidemic diseases but show intense side effects when used at higher dose and/or for a longer duration.


Assuntos
Antifúngicos/química , Cobre/química , Fluconazol/química , Nanocompostos/química , Prata/química , Óxido de Zinco/química , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Tamanho da Partícula
10.
Contemp Clin Dent ; 10(3): 531-541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32308333

RESUMO

CONTEXT: Oral submucous fibrosis (OSMF) is a high-risk premalignant condition of the oral cavity and oropharynx. Complete regression of the disease is still not possible with available treatment modalities. AIMS: The aim of the study was to evaluate the efficacy of curcumin, lycopene, and piperine as a combination in the management of OSMF. SETTINGS AND DESIGN: Efficacy was evaluated on the basis of improvement in clinical parameters (i.e., visual Analog Scale [VAS]) score for burning sensation, mouth opening (MO), mucosal flexibility (MF), and tongue protrusion [TP]). MATERIALS AND METHODS: Forty patients clinically and histopathologically diagnosed with OSMF were included in the study; patients were administered with the above-stated drug combination, and clinical parameters were evaluated at regular intervals to compare the pre- and post-treatment measurements. STATISTICAL ANALYSIS USED: Paired t-test was done to evaluate significance of the results. RESULTS: Highly significant improvement was observed for posttreatment reduction in VAS score for burning sensation and increase in MO (P < 0.001). Significant improvement was also observed in the increase of MF and TP. Posttreatment histopathological evaluation also revealed reepithelialization, indicated by significant increase in the epithelial thickness as found through quantitative image analysis. Immunohistochemical studies with Col1A1 showed decrease in collagen deposition. CONCLUSIONS: Taken together, the present study proposes the usage of combination drug therapy for the management of OSMF as an effective and affordable way.

11.
J Med Chem ; 59(15): 7275-81, 2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27442915

RESUMO

Two novel binaphthyl amines have been designed and synthesized using Buchwald amination and oxidative homocoupling as key steps. The binaphthyl amine containing two triazole rings shows higher affinity for c-MYC G-quadruplex, exhibits fluorescence "turn-on" response with c-MYC, and stains the nucleus in cells. The triazolyl binaphthyl amine shows cytotoxicity for cancer cells by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, both ligands can downregulate c-MYC expression at transcriptional and translational levels.


Assuntos
Aminas/química , Rastreamento de Células , Corantes Fluorescentes/química , Quadruplex G , Naftalenos/química , Proteínas Proto-Oncogênicas c-myc/genética , Aminas/síntese química , Aminas/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Microscopia de Fluorescência , Estrutura Molecular , Naftalenos/síntese química , Naftalenos/farmacologia , Relação Estrutura-Atividade
12.
World J Biol Chem ; 7(1): 158-67, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26981204

RESUMO

Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

13.
Sci Rep ; 5: 13183, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26286633

RESUMO

The c-MYC proto-oncogene is a regulator of fundamental cellular processes such as cell cycle progression and apoptosis. The development of novel c-MYC inhibitors that can act by targeting the c-MYC DNA G-quadruplex at the level of transcription would provide potential insight into structure-based design of small molecules and lead to a promising arena for cancer therapy. Herein we report our finding that two simple bis-triazolylcarbazole derivatives can inhibit c-MYC transcription, possibly by stabilizing the c-MYC G-quadruplex. These compounds are prepared using a facile and modular approach based on Cu(I) catalysed azide and alkyne cycloaddition. A carbazole ligand with carboxamide side chains is found to be microenvironment-sensitive and highly selective for "turn-on" detection of c-MYC quadruplex over duplex DNA. This fluorescent probe is applicable to visualize the cellular nucleus in living cells. Interestingly, the ligand binds to c-MYC in an asymmetric fashion and selects the minor-populated conformer via conformational selection.


Assuntos
Núcleo Celular/metabolismo , Regulação para Baixo , Sondas Moleculares/metabolismo , Neoplasias/genética , Transcrição Gênica , Apoptose/efeitos dos fármacos , Carbazóis/síntese química , Carbazóis/química , Carbazóis/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Citometria de Fluxo , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/metabolismo , Quadruplex G , Humanos , Ligantes , Sondas Moleculares/química , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo
14.
Environ Toxicol ; 30(4): 396-410, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23997012

RESUMO

Sequelae of chronic lead (Pb(2+) ) toxicity includes anemia that is partially due to early death of erythrocytes characterized by excess accumulation of ROS and downregulation of antioxidant system causing oxidative stress and externalization of phosphatidylserine. In this study, pathophysiological based therapeutic application of garlic was evaluated against erythrocyte death. Results suggest that garlic administration prevents oxidative stress, restored the antioxidant balance in erythrocytes of Pb(2+) exposed mice. Moreover, in vitro studies revealed that activity of both scramblase and aminophospholipid translocase could be changed by modifying the critical sulfhydryl groups in presence of dithiothreitol during Pb(2+) exposure. Data also indicated that garlic treatment in Pb(2+) exposed mice exhibited sharp decline in PS exposure and increase in erythrocyte membrane thiol group followed by increase in aminophospholipid translocase activity and decline in scramblase activity. Findings indicated that garlic has the ability to restore the lifespan of erythrocytes during Pb(2+) exposure.


Assuntos
Eritrócitos/efeitos dos fármacos , Alho , Chumbo/toxicidade , Extratos Vegetais/farmacologia , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/metabolismo , Anemia/induzido quimicamente , Anemia/prevenção & controle , Animais , Antioxidantes/metabolismo , Membrana Eritrocítica/química , Eritrócitos/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Fagocitose/efeitos dos fármacos , Fosfatidilserinas/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo
15.
Bioorg Med Chem ; 22(16): 4422-9, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24961873

RESUMO

A modular synthesis of l-proline derived peptidomimetics has been developed using the Cu(I) catalyzed Huisgen cycloaddition between an azido prolinamide with pyridine and benzene dicarboxamide containing dialkynes. Förster Resonance Energy Transfer (FRET) melting assay provided an initial indication that the pyridyl analogue can stabilize the c-KIT1 quadruplex DNA. A competitive FRET-melting assay and Fluorescent Intercalator Displacement (FID) assay suggest that the pyridyl ligand shows excellent selectivity for c-KIT1 quadruplex over duplex DNA and other investigated G-quadruplexes. Molecular docking studies indicate that the pyridyl ligand can adopt unique conformations upon binding to c-KIT1 quadruplex due to the presence of intramolecular hydrogen bonds. The pyridyl ligand can perturb cell cycle progression and induce necrotic cell death of human hepatocellular liver carcinoma HepG2 cells.


Assuntos
Antineoplásicos/farmacologia , Quadruplex G , Neoplasias Hepáticas/patologia , Peptidomiméticos/química , Prolina/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Transferência Ressonante de Energia de Fluorescência , Células Hep G2 , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Prolina/síntese química , Prolina/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
16.
Molecules ; 19(4): 4418-32, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24727415

RESUMO

Modular synthesis of regiospecifically fluorinated 2,4-diene Weinreb amides, with defined stereochemistry at both double bonds, was achieved via two sequential Julia-Kocienski olefinations. In the first step, a Z-a-fluorovinyl Weinreb amide unit with a benzothiazolylsulfanyl substituent at the allylic position was assembled. This was achieved via condensation of two primary building blocks, namely 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (a Julia-Kocienski olefination reagent) and 2-(benzo[d]thiazol-2-ylthio)acetaldehyde (a bifunctional building block). This condensation was highly Z-selective and proceeded in a good 76% yield. Oxidation of benzothiazolylsulfanyl moiety furnished a second-generation Julia-Kocienski olefination reagent, which was used for the introduction of the second olefinic linkage via DBU-mediated condensations with aldehydes, to give (2Z,4E/Z)-dienamides in 50%-74% yield. Although olefinations were 4Z-selective, (2Z,4E/Z)-2-fluoro-2,4-dienamides could be readily isomerized to the corresponding 5-substituted (2Z,4E)-2-fluoro-N-methoxy-N-methylpenta-2,4-dienamides in the presence of catalytic iodine.


Assuntos
Alcenos/síntese química , Amidas/síntese química , Catálise , Halogenação , Estrutura Molecular , Oxirredução , Estereoisomerismo
17.
Alcohol ; 48(2): 123-32, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24507479

RESUMO

Andrographis paniculata (AP) is a traditional medicinal plant of Ayurveda. It grows widely in Asia and is prescribed in the treatment of liver diseases. Here we have investigated the beneficial role of 14-deoxyandrographolide (14-DAG), a bioactive diterpenoid from AP, against alcoholic steatosis in rats. 14-DAG was extracted from aerial parts (leaves and stems) of AP. Rats were fed with ethanol for 8 weeks. Animals were treated with 14-DAG during the last 4 weeks of ethanol treatment. In vitro studies were undertaken in a human hepatocellular liver carcinoma cell line culture. Hepatosteatosis was assessed from histopathological studies of liver sections. Acetyl-CoA, malonyl-CoA, and triglyceride contents were determined using commercially available kits. Fatty acid synthesis was evaluated from incorporation of 1-(14)C acetate. Regulation of fatty acid oxidation and lipogenesis were monitored with immunoblotting and immunoprecipitation studies. Ethanol exposure led to hepatotoxicity, as evident from the marked enhancement in the levels of AST and ALT. The values decreased almost to control levels in response to 14-DAG treatment. Results showed that ethanol feeding induced deactivation of AMP-activated protein kinase (AMPK) that led to enhanced lipid synthesis and decreased fatty acid oxidation, culminating in hepatic fat accumulation. Treatment with 14-DAG activated AMPK through induction of cyclic AMP-protein kinase A pathway. Activation of AMPK was followed by down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase, leading to suppression of lipogenesis. This was associated with up-regulation of sirtuin 1 and depletion of malonyl-CoA, in favor of increased fatty acid oxidation. 14-DAG controlled ethanol-induced hepatosteatosis by interfering with dysregulation of lipid metabolism. In conclusion, our results indicated that 14-DAG was capable of preventing the development of fatty liver through AMPK-mediated regulation of lipid metabolism. This finding supported the hepatoprotective role of 14-DAG, which might serve as a therapeutic option to alleviate hepatosteatosis in chronic alcoholism.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diterpenos/uso terapêutico , Etanol/toxicidade , Fígado Gorduroso Alcoólico/prevenção & controle , Acetil-CoA Carboxilase/metabolismo , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação para Baixo , Feminino , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Regulação para Cima
18.
Food Chem Toxicol ; 59: 236-48, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23764359

RESUMO

Chronic alcoholism is one of the most common causes of liver diseases worldwide. Nitric oxide (NO) has been proposed to have potential for clinical application against chronic hepatocellular injuries. However, mechanisms underlying hepatoprotective functions of NO in ethanol-induced apoptosis are largely unknown. Sprauge-Dawley rats were exposed to ethanol for 8 weeks. Half of the ethanol-fed animals received 14-deoxyandrographolide (14-DAG) treatment for the last 4 weeks of study. Preventive effect of 14-DAG against ethanol-induced hepatotoxicity involved constitutive nitric oxide synthase (cNOS) activation followed by up-regulation of γ-glutamylcysteine synthetase activity and reduced oxidative stress. Enhanced interaction of cNOS with caveolin-1 caused down-regulation of enzyme activity and led to depletion of NO in the hepatocytes of ethanol-fed animals. 14-DAG acted as activator of adenylate cyclase and modulated cyclic AMP (cAMP) mediated expression of caveolin-1 and calmodulin. This eventually favored activation of cNOS through inhibition of cNOS-caveolin-1 interaction. Our results suggest that, protective effect of 14-DAG against ethanol-induced hepatic injury is based on its ability to reduce oxidative stress through cNOS dependent improvement of redox status. 14-DAG mediated activation of adenylate cyclase-cAMP signaling leading to up-regulation of cNOS may provide a promising approach in the prevention of liver diseases during chronic alcoholism.


Assuntos
Adenilil Ciclases/metabolismo , Antioxidantes/uso terapêutico , Diterpenos/uso terapêutico , Hepatopatias Alcoólicas/prevenção & controle , Fígado/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Adenilil Ciclases/química , Andrographis/química , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/agonistas , AMP Cíclico/metabolismo , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Feminino , Glutamato-Cisteína Ligase/química , Glutamato-Cisteína Ligase/metabolismo , Células Hep G2 , Humanos , Fígado/citologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Óxido Nítrico/agonistas , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/química , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley
19.
J Hazard Mater ; 248-249: 238-45, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23385204

RESUMO

Carbon nanoparticles continuously generated from industries and vehicles due to incomplete combustion of fuels is one of the potent causes of air pollution. The exposure of this polluted air with carbon nanoparticles, introduced into the bloodstream of animals in the course of respiration, motivated us to study their interaction with plasma proteins, bovine serum albumin and human serum albumin. Carbon nanoparticles with very small size and high purity were synthesized by dehydration of d-glucose using concentrated sulphuric acid as dehydrating agent. These were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction, Raman spectroscopy, FTIR spectroscopy and UV-visible spectroscopy. Carbon nanoparticles-protein interactions were studied by fluorescence spectroscopy, circular dichroism spectroscopy and isothermal titration calorimetry. The fluorescence quenching constants and thermodynamic parameters such as enthalpy change (ΔH°), entropy change (ΔS°) and free energy change (ΔG°) were calculated, which indicated a strong static quenching and primary electrostatic interaction between the carbon nanoparticles and blood proteins. Circular dichroism spectra provided the information about the secondary structure alteration of the proteins in presence of carbon nanoparticles. These findings have shed light towards an understanding of the interactions between carbon nanoparticles and serum proteins which may clarify the potential risks and undesirable health effects of carbon nanoparticles, as well as the related cellular trafficking and systemic translocation.


Assuntos
Carbono/química , Nanopartículas/química , Albumina Sérica/química , Animais , Calorimetria , Bovinos , Humanos , Conformação Proteica , Análise Espectral/métodos , Termodinâmica
20.
Tetrahedron Lett ; 54(45): 6008-6011, 2013 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25568501

RESUMO

A Julia-Kocienski approach to trifluoromethyl-substituted alkenes was evaluated in the reactions of 1,3-benzothiazol-2-yl, 1-phenyl-1H-tetrazol-5-yl, and 1-tbutyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfones with aldehydes. Among the various conditions tested, the best yields were obtained with 1-phenyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfone, in CsF-mediated, room temperature olefinations in DMSO. Aromatic aldehydes gave (trifluoromethyl)vinyl derivatives in 23-86% yields, with generally moderate stereoselectivity. Straightforward synthesis of the Julia-Kocienski reagent, and conversion to trifluoromethyl-substituted alkenes under mild reaction conditions, are the advantages of this approach.

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