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1.
Sci Rep ; 14(1): 15178, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987553

RESUMO

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.


Assuntos
Adesão Celular , Materiais Revestidos Biocompatíveis , Propilaminas , Silanos , Stents , Trombose , Silanos/química , Silanos/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Humanos , Stents/efeitos adversos , Suínos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Propilaminas/farmacologia , Propilaminas/química , Adsorção , Trombose/prevenção & controle , Fibrinolíticos/farmacologia , Fibrinolíticos/química , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo
2.
J Environ Sci (China) ; 146: 39-54, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38969461

RESUMO

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.


Assuntos
Césio , Ferrocianetos , Nanofibras , Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Ferrocianetos/química , Nanofibras/química , Poluentes Químicos da Água/química , Césio/química , Adsorção , Purificação da Água/métodos , Nanopartículas/química , Dióxido de Silício/química , Cinética , Propilaminas/química , Silanos
3.
J Environ Manage ; 365: 121603, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38963967

RESUMO

Water treatment has turned out to be more important in most societies due to the expansion of most economies and to advancement of industrialization. Developing efficient materials and technologies for water treatment is of high interest. Thin film nanocomposite membranes are regarded as the most effective membranes available for salts, hydrocarbon, and environmental pollutants removal. These membranes improve productivity while using less energy than conventional asymmetric membranes. Here, the polyvinylidene fluoride (PVDF) membranes have been successfully modified via dip single-step coating by silica-aminopropyl triethoxysilane/trimesic acid/melamine nanocomposite (Si-APTES-TA-MM). The developed membranes were evaluated for separating the emulsified oil/water mixture, the surface wettability of the membrane materials is therefore essential. During the conditioning step, that is when the freshwater was introduced, the prepared membrane reached a flux of about 27.77 L m-2 h-1. However, when the contaminated water was introduced, the flux reached 18 L m-2 h-1, alongside an applied pressure of 400 kPa. Interestingly, during the first 8 h of the filtration test, the membrane showed 90 % rejection for ions including Mg2+, and SO42- and ≈100 % for organic pollutants including pentane, isooctane, toluene, and hexadecane. Also, the membrane showed 98 % rejection for heavy metals including strontium, lead, and cobalt ions. As per the results, the membrane could be recommended as a promising candidate to be used for a mixture of salt ions, hydrocarbons, and mixtures of heavy metals from wastewater.


Assuntos
Membranas Artificiais , Silanos , Poluentes Químicos da Água , Purificação da Água , Purificação da Água/métodos , Silanos/química , Poluentes Químicos da Água/química , Metais/química , Óleos/química , Propilaminas/química , Sais/química , Interações Hidrofóbicas e Hidrofílicas , Íons , Polivinil/química
4.
Molecules ; 29(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893361

RESUMO

A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski's rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson's disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.


Assuntos
Alcinos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores da Monoaminoxidase , Monoaminoxidase , Pargilina , Alcinos/química , Alcinos/farmacologia , Monoaminoxidase/metabolismo , Monoaminoxidase/química , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/síntese química , Humanos , Pargilina/química , Pargilina/análogos & derivados , Pargilina/farmacologia , Propilaminas/química , Relação Estrutura-Atividade , Estrutura Molecular
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124542, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38823241

RESUMO

Enzyme-induced in-situ fluorescence is crucial for the development of biosensing mechanisms and correlative spectroscopic analysis. Inspired by simple p-aminophenol (AP)-controlled synthesis and the specific catalytic reaction of 4-aminophenyl phosphate (APP) triggered by alkaline phosphatase (ALP), our research proposed a strategy to prepare carbon dots (CDs) as fluorescent signals for ALP detection using AP and 3-aminopropyltrimethoxysilane (APTMS) as the precursors. The further constructed ratiometric fluorescence sensor reduced the detection limit of ALP to 0.075 µU/mL by a significant margin. Considering the need for point-of-care testing (POCT), we chose agarose for the preparation of portable hydrogel sensors so that even untrained personnel can quickly achieve semi-quantitative visual detection of ALP using colorimetric cards. These results demonstrate the practical applicability of ratiometric fluorescence sensing hydrogel pillar arrays, which are important for high-sensitivity, visualization, and portable rapid enzyme activity assays.


Assuntos
Fosfatase Alcalina , Técnicas Biossensoriais , Hidrogéis , Espectrometria de Fluorescência , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/análise , Técnicas Biossensoriais/métodos , Espectrometria de Fluorescência/métodos , Hidrogéis/química , Limite de Detecção , Silanos/química , Pontos Quânticos/química , Carbono/química , Propilaminas/química , Colorimetria/métodos , Humanos
6.
Int J Biol Macromol ; 274(Pt 1): 133414, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925183

RESUMO

A facial strategy of co-deposition is proposed to enhance the interfacial bonding in wood fiber (WF)/polylactic acid (PLA) composites. Dopamine or tannic acid (TA) was co-deposited with 3-aminopropyltriethoxysilane (APTES) onto the WF surface to create active coatings. These coatings were formed through Michael addition and Schiff base reactions and effectively attached to the WF through a combination of hydrogen and covalent bonding. Such active coatings facilitated the connection between WF and PLA through both covalent bonds and physical entanglements, thereby enhancing the interfacial interactions and compatibility between the two components. The co-deposition of TA with APTES was found to be more effective than with dopamine, leading to a dramatic improvement in the tensile strength and elongation at break of the composites by 33.4 % and 185.9 %, respectively. This work offers a facile method to prepare high performance plant fiber reinforced PLA composites, thereby broadening the potential applications of PLA.


Assuntos
Poliésteres , Resistência à Tração , Madeira , Poliésteres/química , Madeira/química , Silanos/química , Taninos/química , Teste de Materiais , Propilaminas/química
7.
Analyst ; 149(12): 3317-3324, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38742381

RESUMO

In this work, the release of giant liposome (∼100 µm in diameter) content was imaged by shadow electrochemiluminescence (ECL) microscopy. Giant unilamellar liposomes were pre-loaded with a sucrose solution and allowed to sediment at an ITO electrode surface immersed in a solution containing a luminophore ([Ru(bpy)3]2+) and a sacrificial co-reactant (tri-n-propylamine). Upon polarization, the electrode exhibited illumination over its entire surface thanks to the oxidation of ECL reagents. However, as soon as liposomes reached the electrode surface, dark spots appeared and then spread over time on the surface. This observation reflected a blockage of the electrode surface at the contact point between the liposome and the electrode surface, followed by the dilution of ECL reagents after the rupture of the liposome membrane and release of its internal ECL-inactive solution. Interestingly, ECL reappeared in areas where it initially faded, indicating back-diffusion of ECL reagents towards the previously diluted area and thus confirming liposome permeabilization. The whole process was analyzed qualitatively and quantitatively within the defined region of interest. Two mass transport regimes were identified: a gravity-driven spreading process when the liposome releases its content leading to ECL vanishing and a diffusive regime when ECL recovers. The reported shadow ECL microscopy should find promising applications for the imaging of transient events such as molecular species released by artificial or biological vesicles.


Assuntos
Eletrodos , Medições Luminescentes , Medições Luminescentes/métodos , Lipossomos/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Propilaminas/química , Lipossomas Unilamelares/química , Sacarose/química , Compostos de Estanho
8.
Analyst ; 149(13): 3615-3624, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38775016

RESUMO

Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is extremely important to be conscious that MpM can raise the risk of severe infections and some cancers if it exceeds the recommended dose while lower doses will result in organ rejections. So, it is essential to monitor the dosage of MpM in real time in the micromolar range. In this work, we have synthesized 3-aminopropyltriethoxysilane (APTES) functionalized nickel cobaltite (NiCo2O4) and this amino functionalization was chosen to enhance the stability and electrochemical activity of NiCo2O4. The enhanced activity of NiCo2O4 was used for developing an electrochemical sensor for the detection of MpM. APTES functionalized NiCo2O4 was coated on carbon cloth and used as the working electrode. Surface functionalization with APTES on NiCo2O4 was aimed at augmenting the adsorption/interaction of MpM due to its binding properties. The developed sensor showed a very low detection limit of 1.23 nM with linear ranges of 10-100 nM and 1-100 µM and its practical applicability was examined using artificial samples of blood serum and cerebrospinal fluid, validating its potential application in real-life scenarios.


Assuntos
Carbono , Imunossupressores , Limite de Detecção , Ácido Micofenólico , Nanoestruturas , Níquel , Ouriços-do-Mar , Dispositivos Eletrônicos Vestíveis , Animais , Níquel/química , Ácido Micofenólico/sangue , Ácido Micofenólico/química , Ácido Micofenólico/análise , Imunossupressores/sangue , Imunossupressores/análise , Imunossupressores/química , Carbono/química , Ouriços-do-Mar/química , Nanoestruturas/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Propilaminas/química , Humanos , Cobalto/química , Eletrodos , Silanos
9.
Int J Biol Macromol ; 269(Pt 1): 132021, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38697441

RESUMO

Challenges in enzyme and product recovery are currently intriguing in modern biotechnology. Coping enzyme stability, shelf life and efficiency, nanomaterials-based immobilization were epitomized of industrial practice. Herein, a α-amylase from Geobacillus thermoleovorans was purified and bound effectively on to a modified 3-Aminopropyltriethoxysilane (APTES)-Fe3O4 nanoparticle. It was revealed that the carrier-bound enzyme catalysis (pH 8 and 60 °C) was significant in contrast to the free enzyme (pH 7.5 and 55 °C). Furthermore, Zn2+ and Cu2+ were shown to cause inhibitory effects in both enzyme states. Unlike chloroform, toluene, benzene, and butanol, minimal effects were observed with ethanol, acetone, and hexane. The bound enzyme retained 27.4 % of its initial activity after being stored for 36 days. In addition, the reusability of the bound enzyme showed a gradual decline in activity after the first cycle; however, after 13 cycles, its residual activity at 53 % was observed. These data proved significant enough to use this enzyme for industrial starch and analogous substrate bio-processing.


Assuntos
Estabilidade Enzimática , Enzimas Imobilizadas , Propilaminas , alfa-Amilases , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , alfa-Amilases/química , alfa-Amilases/metabolismo , Propilaminas/química , Silanos/química , Geobacillus/enzimologia , Temperatura , Concentração de Íons de Hidrogênio , Biocatálise , Catálise , Nanopartículas de Magnetita/química , Amido/química
10.
Colloids Surf B Biointerfaces ; 239: 113975, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38762934

RESUMO

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.


Assuntos
Durapatita , Európio , Ácido Fólico , Nanopartículas , Humanos , Ácido Fólico/química , Európio/química , Nanopartículas/química , Células HeLa , Durapatita/química , Luminescência , Microscopia de Fluorescência , Propilaminas/química , Tamanho da Partícula , Substâncias Luminescentes/química
11.
ACS Biomater Sci Eng ; 10(5): 3057-3068, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38641433

RESUMO

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.


Assuntos
Catéteres , Materiais Revestidos Biocompatíveis , Heparina , Polifenóis , Taninos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Catéteres/microbiologia , Polifenóis/química , Polifenóis/farmacologia , Heparina/química , Heparina/farmacologia , Taninos/química , Taninos/farmacologia , Silanos/química , Silanos/farmacologia , Anticoagulantes/química , Anticoagulantes/farmacologia , Propilaminas/química , Aminas/química , Aminas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Polilisina/química , Polilisina/farmacologia , Propriedades de Superfície , Interações Hidrofóbicas e Hidrofílicas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Elastômeros de Silicone/química , Adsorção , Escherichia coli/efeitos dos fármacos
12.
Int J Biol Macromol ; 268(Pt 2): 131790, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677693

RESUMO

The demand for paper-based packaging materials as an alternative to incumbent disposable petroleum-derived polymers for food packaging applications is ever-growing. However, typical paper-based formats are not suitable for use in unconventional applications due to inherent limitations (e.g., excessive hydrophilicity, lack antimicrobial ability), and accordingly, enabling new capabilities is necessity. Herein, a simple and environmentally friendly strategy was proposed to introduce antimicrobial and hydrophobic functions to cellulose paper through successive chemical grafting of 3-aminopropyltriethoxysilane (APS) and cinnamaldehyde (CA). The results revealed that cellulose paper not only showed long-term antibacterial effect on different bacteria, but also inhibited a wide range of fungi. Encouragingly, the modified paper, which is fluorine-free, displays a high contact angle of 119.7°. Thus, even in the wet state, the modified paper can still maintain good mechanical strength. Meanwhile, the multifunctional composite papers have excellent biocompatibility and biodegradability. Compared with ordinary cellulose paper, multifunctional composite paper can effectively prolong the shelf life of strawberries. Therefore, the multifunctional composite paper represents good application potential as a fruit packaging material.


Assuntos
Acroleína , Celulose , Embalagem de Alimentos , Fragaria , Interações Hidrofóbicas e Hidrofílicas , Papel , Celulose/química , Celulose/análogos & derivados , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Fragaria/microbiologia , Embalagem de Alimentos/métodos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Silanos/química , Conservação de Alimentos/métodos , Propilaminas/química , Testes de Sensibilidade Microbiana
13.
Biomed Phys Eng Express ; 10(4)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38479000

RESUMO

Diagnosis of diseases with low facilities, speed, accuracy and sensitivity is an important matter in treatment. Bioprobes based on iron oxide nanoparticles are a good candidate for early detection of deadly and infectious diseases such as tetanus due to their high reactivity, biocompatibility, low production cost and sample separation under a magnetic field. In this study, silane groups were coated on surface of iron oxide nanoparticles using tetraethoxysilane (TEOS) hydrolysis. Also, NH2groups were generated on the surface of silanized nanoparticles using 3-aminopropyl triethoxy silane (APTES). Antibody was immobilized on the surface of silanized nanoparticles using TCT trichlorothriazine as activator. Silanization and stabilized antibody were investigated by using of FT-IR, EDX, VSM, SRB technique. UV/vis spectroscopy, fluorescence, agglutination test and ELISA were used for biosensor performance and specificity. The results of FT-IR spectroscopy showed that Si-O-Si and Si-O-Fe bonds and TCT chlorine and amine groups of tetanus anti-toxoid antibodies were formed on the surface of iron oxide nanoparticles. The presence of Si, N and C elements in EDX analysis confirms the silanization of iron oxide nanoparticles. VSM results showed that the amount of magnetic nanoparticles after conjugation is sufficient for biological applications. Antibody stabilization on nanoparticles increased the adsorption intensity in the uv/vis spectrometer. The fluorescence intensity of nano bioprobe increased in the presence of 10 ng ml-1. Nanobio probes were observed as agglomerates in the presence of tetanus toxoid antigen. The presence of tetanus antigen caused the formation of antigen-nanobioprobe antigen complex. Identification of this complex by HRP-bound antibody confirmed the specificity of nanobioprobe. Tetanus magnetic nanobioprobe with a diagnostic limit of 10 ng ml-1of tetanus antigen in a short time can be a good tool in LOC devices and microfluidic chips.


Assuntos
Técnicas Biossensoriais , Propilaminas , Silanos , Toxoide Tetânico , Toxoide Tetânico/química , Toxoide Tetânico/imunologia , Silanos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Técnicas Biossensoriais/métodos , Propilaminas/química , Humanos , Ensaio de Imunoadsorção Enzimática , Nanopartículas Magnéticas de Óxido de Ferro/química , Tétano/diagnóstico , Tétano/prevenção & controle , Nanopartículas de Magnetita/química , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Limite de Detecção , Ferro/química , Testes de Aglutinação/métodos
14.
Steroids ; 198: 109272, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37468115

RESUMO

Allopregnanolone (AP) is a neurosteroid synthesized in the brain and a positive allosteric modulator of γ-aminobutyric acid (GABA) type A receptors. Some drugs possessing the aryloxypropanamine (AOPA) pharmacophore, such as fluoxetine, exert their central nervous system (CNS) effects by increasing the brain AP. Although duloxetine (DLX), dapoxetine (DPX), atomoxetine (ATX) and propranolol (PRL) also possess the AOPA pharmacophore and are used to treat some psychiatric disorders, the capabilities of these drugs to increase the brain AP and the possible involvement of AP in their CNS effects remain to be fully elucidated. To clarify these points, we first developed a method for quantifying AP in the rat brain by liquid chromatography/electrospray ionization-tandem mass spectrometry. Analysis of the changes in the brain AP levels using this method revealed that the intraperitoneal administration of DLX (10 mg/kg), DPX (10 mg/kg) and PRL (20 mg/kg) significantly increased the brain AP (DLX: < 0.40-2.74 ng/g tissue, DPX: 1.48-3.83 ng/g tissue and PRL: < 0.40-2.09 ng/g tissue) compared to the saline administration (<0.40 ng/g tissue). These results suggested the possible involvement of the GABAergic neurosteroid, AP, in the central actions of DLX, DPX and PRL. In contrast, ATX (10 mg/kg) did not affect the AP levels in the brain. In addition, the brain and serum AP levels had a remarkably high positive correlation after the administration of DLX, DPX and PRL. Thus, this study proposed the AP-related novel mechanism of actions of DLX, DPX and PRL in the CNS.


Assuntos
Neuroesteroides , Pregnanolona , Animais , Ratos , Encéfalo , Cloridrato de Duloxetina/farmacologia , Preparações Farmacêuticas , Farmacóforo , Pregnanolona/farmacologia , Propranolol/farmacologia , Propilaminas/química , Propilaminas/farmacologia
15.
Future Med Chem ; 15(2): 211-224, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36802855

RESUMO

Propargylamine is a chemical moiety whose properties have made it a widely distributed group within the fields of medicinal chemistry and chemical biology. Its particular reactivity has traditionally popularized the preparation of propargylamine derivatives using a large variety of synthetic strategies, which have facilitated the access to these compounds for the study of their biomedical potential. This review comprehensively covers and analyzes the applications that propargylamine-based derivatives have achieved in the drug discovery field, both from a medicinal chemistry perspective and from a chemical biology-oriented approach. The principal therapeutic fields where propargylamine-based compounds have made an impact are identified, and a discussion of their influence and growing potential is included.


Assuntos
Descoberta de Drogas , Pargilina , Pargilina/farmacologia , Pargilina/química , Propilaminas/química
16.
Langmuir ; 38(50): 15662-15671, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36480813

RESUMO

The present study reports on the synthesis of a new alkoxysilane-bearing light-responsive cinnamyl group and its application as a surface functionalization agent for the development of SiO2 nanoparticles (NPs) with photoreversible tails. In detail, cinnamic acid (CINN) was activated with N-hydroxysuccinimide (NHS) to obtain the corresponding NHS-ester (CINN-NHS). Subsequently, the amine group of 3-aminopropyltriethoxysilane (APTES) was acylated with CINN-NHS leading to the generation of a novel organosilane, CINN-APTES, which was then exploited for decorating SiO2 NPs. The covalent bond to the silica surface was confirmed by solid state NMR, whereas thermogravimetric analysis unveiled a functionalization degree much higher compared to that achieved by a conventional double-step post-grafting procedure. In light of these intriguing results, the strategy was successfully extended to naturally occurring sepiolite fibers, widely employed as fillers in technological applications. Finally, a preliminary proof of concept of the photoreversibility of the obtained SiO2@CINN-APTES system has been carried out through UV diffuse reflectance. The overall outcomes prove the consistency and the versatility of the methodological protocol adopted, which appears promising for the design of hybrid NPs to be employed as building blocks for photoresponsive materials with the ability to change their molecular structure and subsequent properties when exposed to different light stimuli.


Assuntos
Nanopartículas Multifuncionais , Nanopartículas , Dióxido de Silício/química , Propilaminas/química , Nanopartículas/química
17.
J Org Chem ; 87(21): 14223-14229, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36282953

RESUMO

The preparation, structure, physical properties, and reactivities of sodium isopropyl(trimethylsilyl)amide (NaPTA) are described. The solubilities at room temperature range from n-heptane (0.55 M), n-hexane (0.60 M), toluene (0.65 M), MTBE (1.7 M), Et3N (3.2 M), and THF (>6.0 M). The half-life to destruction in neat THF is >1 year at 25 °C and 7 days at 70 °C, which compares favorably to 2.5 months and 1.5 days, respectively, for LDA in neat THF. This study focuses on NaPTA in THF. 29Si NMR spectroscopy shows exclusively a mixture of cis and trans stereoisomeric dimers in 0.10-12 M THF in hexane. Density functional theory (DFT) computations suggest that the pKb is intermediate between dimeric sodium diisopropylamide (NaDA) and dimeric sodium hexamethyldisilazide (NaHMDS). Metalations of arenes, epoxides, ketones, hydrazones, alkenes, and alkyl halides show higher reactivities than LDA (kNaPTA/LDA = 1-30). While the rates of arene metalation are high, the lower pKb of NaPTA limits the substrates. Metalation of pseudoephedrate-based carboxamides to form disodiated Myers enolates solves several challenging technical problems.


Assuntos
Amidas , Sódio , Sódio/química , Propilaminas/química , Íons , Lítio/química
18.
J Med Chem ; 65(3): 2208-2224, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35005974

RESUMO

Glioma treatment remains a challenge with a low survival rate due to the lack of effective therapeutics. Monoamine oxidase A (MAO A) plays a role in glioma development, and MAO A inhibitors reduce glioma growth. Histone deacetylase (HDAC) inhibition has emerged as a promising therapy for various malignancies including gliomas. We have synthesized and evaluated N-methylpropargylamine-conjugated hydroxamic acids as dual inhibitors of MAO A and HDAC. Compounds display potent MAO A inhibition with IC50 from 0.03 to <0.0001 µM and inhibit HDAC isoforms and cell growth in the micromolar to nanomolar IC50 range. These selective MAO A inhibitors increase histone H3 and α-tubulin acetylation and induce cell death via nonapoptotic mechanisms. Treatment with 15 reduced tumor size, reduced MAO A activity in brain and tumor tissues, and prolonged the survival. This first report on dual inhibitors of MAO A and HDAC establishes the basis of translational research for an improved treatment of glioma.


Assuntos
Inibidores Enzimáticos/química , Histona Desacetilases/química , Ácidos Hidroxâmicos/química , Monoaminoxidase/química , Acetilação/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Glioma/tratamento farmacológico , Glioma/mortalidade , Histona Desacetilases/metabolismo , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/metabolismo , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoaminoxidase/metabolismo , Pargilina/análogos & derivados , Pargilina/química , Propilaminas/química , Relação Estrutura-Atividade , Transplante Heterólogo
19.
Carbohydr Polym ; 275: 118701, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742427

RESUMO

Most cellulose products lack water resistance due to the existence of abundant hydroxyl groups. In this work, microfibrillated cellulose (MFC) was modified via 3-aminopropyltriethoxysilane (APTES)-assisted ball milling. Under the synergism between high-energy mechanical force field and APTES-modification, the fibrillation and hydrophobization of MFC were achieved simultaneously. Free-standing translucent cellulose films made of modified MFC were fabricated. The original crystal form of cellulose is maintained. The hydrophobicity of cellulose film markedly increases and the water contact angle goes up to 133.2 ± 3.4°, which might be ascribed to the combined effects of APTES-modification and rough film surface. In addition, the thermostability and mechanical properties of cellulose film are also improved via mechanochemical modification. This work provides a novel one-step fibrillation-hydrophobization method for cellulose.


Assuntos
Celulose/química , Propilaminas/química , Silanos/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Propriedades de Superfície , Água/química
20.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641270

RESUMO

The conjugation of biomolecules to magnetic nanoparticles has emerged as promising approach in biomedicine as the treatment of several diseases, such as cancer. In this study, conjugation of bioactive peptide fractions from germinated soybeans to magnetite nanoparticles was achieved. Different fractions of germinated soybean peptides (>10 kDa and 5-10 kDa) were for the first time conjugated to previously coated magnetite nanoparticles (with 3-aminopropyltriethoxysilane (APTES) and sodium citrate) by the Ugi four-component reaction. The crystallinity of the nanoparticles was corroborated by X-ray diffraction, while the particle size was determined by scanning transmission electron microscopy. The analyses were carried out using infrared and ultraviolet-visible spectroscopy, dynamic light scattering, and thermogravimetry, which confirmed the coating and functionalization of the magnetite nanoparticles and conjugation of different peptide fractions on their surfaces. The antioxidant activity of the conjugates was determined by the reducing power and hydroxyl radical scavenging activity. The nanoparticles synthesized represent promising materials, as they have found applications in bionanotechnology for enhanced treatment of diseases, such as cancer, due to a higher antioxidant capacity than that of fractions without conjugation. The highest antioxidant capacity was observed for a >10 kDa peptide fraction conjugated to the magnetite nanoparticles coated with APTES.


Assuntos
Antioxidantes/farmacologia , Glycine max/química , Nanopartículas de Magnetita/química , Peptídeos/farmacologia , Antioxidantes/química , Sequestradores de Radicais Livres/química , Germinação , Tamanho da Partícula , Peptídeos/química , Propilaminas/química , Silanos/química , Citrato de Sódio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios X
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