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1.
AAPS PharmSciTech ; 25(6): 161, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38992175

RESUMEN

Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389 nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm2/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.


Asunto(s)
Carbamatos , Nanopartículas , Tamaño de la Partícula , Piperidinas , Solubilidad , Suspensiones , Nanopartículas/química , Piperidinas/química , Piperidinas/administración & dosificación , Piperidinas/farmacocinética , Carbamatos/química , Carbamatos/administración & dosificación , Carbamatos/farmacocinética , Animales , Química Farmacéutica/métodos , Liberación de Fármacos , Polivinilos/química , Polímeros/química , Administración Bucal , Polietilenglicoles/química , Composición de Medicamentos/métodos
2.
J Chem Inf Model ; 64(13): 5140-5150, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973304

RESUMEN

Beta-N-methylamino-l-alanine (BMAA) is a potential neurotoxic nonprotein amino acid, which can reach the human body through the food chain. When BMAA interacts with bicarbonate in the human body, carbamate adducts are produced, which share a high structural similarity with the neurotransmitter glutamate. It is believed that BMAA and its l-carbamate adducts bind in the glutamate binding site of ionotropic glutamate receptor 2 (GluR2). Chronic exposure to BMAA and its adducts could cause neurological illness such as neurodegenerative diseases. However, the mechanism of BMAA action and its carbamate adducts bound to GluR2 has not yet been elucidated. Here, we investigate the binding modes and the affinity of BMAA and its carbamate adducts to GluR2 in comparison to the natural agonist, glutamate, to understand whether these can act as GluR2 modulators. Initially, we perform molecular dynamics simulations of BMAA and its carbamate adducts bound to GluR2 to examine the stability of the ligands in the S1/S2 ligand-binding core of the receptor. In addition, we utilize alchemical free energy calculations to compute the difference in the free energy of binding of the beta-carbamate adduct of BMAA to GluR2 compared to that of glutamate. Our findings indicate that carbamate adducts of BMAA and glutamate remain stable in the binding site of the GluR2 compared to BMAA. Additionally, alchemical free energy results reveal that glutamate and the beta-carbamate adduct of BMAA have comparable binding affinity to the GluR2. These results provide a rationale that BMAA carbamate adducts may be, in fact, the modulators of GluR2 and not BMAA itself.


Asunto(s)
Aminoácidos Diaminos , Carbamatos , Toxinas de Cianobacterias , Receptores AMPA , Receptores AMPA/metabolismo , Receptores AMPA/química , Aminoácidos Diaminos/química , Aminoácidos Diaminos/metabolismo , Carbamatos/química , Carbamatos/metabolismo , Simulación de Dinámica Molecular , Humanos , Sitios de Unión , Unión Proteica , Ácido Glutámico/metabolismo , Ácido Glutámico/química , Ligandos
3.
J Nanobiotechnology ; 22(1): 349, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902761

RESUMEN

Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new route for efficient control of diseases. Most commercial compound formulations are open systems with non-adjustable released rates, resulting in a high frequency of applications. Meanwhile, although nano pesticide delivery systems constructed with different carrier materials have been extensively studied, realizing their actual scale-up production still has important practical significance due to the large-scale field application. In this study, a boscalid and pyraclostrobin dual-loaded nano pesticide system (BPDN) was constructed with industrial-grade carrier materials to facilitate the realization of large-scale production. The optimal industrial-scale preparation mechanism of BPDN was studied with surfactants as key factors. When agricultural emulsifier No.600 and polycarboxylate are used as the ratio of 1:2 in the preparation process, the BPDN has a spherical structure with an average size of 270 nm and exhibits superior physical stability. Compared with commercial formulation, BPDN maintains rate-stabilized release up to 5 times longer, exhibits better dispersion and spreading performance on foliar, has more than 20% higher deposition amounts, and reduces loss. A single application of BPDN could efficiently control tomato gray mold during the growing period of tomatoes due to extended duration and combinatory effectiveness, reducing two application times and labor costs. Toxicology tests on various objects systematically demonstrated that BPDN has improved safety for HepG2 cells, and nontarget organism earthworms. This research provides insight into creating safe, efficient, and environmentally friendly pesticide production to reduce manual operation times and labor costs. Accompanied by production strategies that can be easily scaled up industrially, this contributes to the efficient use of resources for sustainable agriculture.


Asunto(s)
Plaguicidas , Estrobilurinas , Plaguicidas/química , Humanos , Portadores de Fármacos/química , Animales , Carbamatos/química , Tensoactivos/química , Nanopartículas/química , Tamaño de la Partícula , Solanum lycopersicum , Compuestos de Bifenilo , Niacinamida/análogos & derivados
4.
Molecules ; 29(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38893461

RESUMEN

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.


Asunto(s)
Carbamatos , Imidazoles , Trichomonas vaginalis , Trichomonas vaginalis/efectos de los fármacos , Trichomonas vaginalis/genética , Trichomonas vaginalis/crecimiento & desarrollo , Imidazoles/farmacología , Imidazoles/química , Humanos , Carbamatos/farmacología , Carbamatos/química , Metronidazol/farmacología , Metronidazol/química , Regulación de la Expresión Génica/efectos de los fármacos , Trofozoítos/efectos de los fármacos
5.
Anal Chem ; 96(24): 9885-9893, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38848670

RESUMEN

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.


Asunto(s)
Arginina , Glutatión , Oxidación-Reducción , Espectrometría de Masas en Tándem , Animales , Arginina/metabolismo , Arginina/análisis , Arginina/química , Glutatión/metabolismo , Glutatión/análisis , Ratones , Espectrometría de Masas en Tándem/métodos , Células RAW 264.7 , Carbamatos/metabolismo , Carbamatos/química , Cromatografía Líquida de Alta Presión , Lipopolisacáridos/farmacología , Aminoquinolinas/química
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124586, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38833886

RESUMEN

Pesticides, including fungicides, are one of the important groups of environmental toxins that affect human and animal health. Studies have shown that these compounds are considered chemical pollutants. Carbendazim is a systemic fungicide. Unfortunately, excessive use of carbendazim has caused environmental pollution all over the world. In this study, the effect of carbendazim on the enzyme elastase (secreted from the endocrine gland of the pancreas) has been investigated. In a study, the performance and reaction of carbendazim with elastase were investigated using spectroscopic techniques. The stability and structure of elastase enzymes were studied under the influence of carbendazim. The results of fluorescence emission and UV-visible absorption spectrum showed that in the presence of carbendazim, there is an increase in UV-Vis absorption and a decrease in the intensity of the intrinsic fluorescence emission in the protein spectrum. Additionally, a decrease in the thermal stability of elastase was observed in the presence of carbendazim. The stability and structure of elastase enzyme were investigated in the presence of carbendazim. The results revealed that the UV-Vis absorption increased due to the presence of carbendazim, as indicated by the hyperchromic spectrum at 220 and 280 nm peaks. Additionally, the intrinsic fluorescence emission in the protein spectrum decreased with increasing carbendazim concentration at three different temperatures (298, 303, and 313 K). Moreover, the study demonstrated that the TM decreased from 2.59 to 4.58 with the increase of carbendazim, suggesting a decrease in the stability of the elastase structure in response to the elevated carbendazim concentration. According to the results of the research, the interaction between elastase and carbendazim has occurred, and changes have been made in the enzyme under the influence of carbendazim. The formation of the complex between elastase and carbendazim was consistent with the results obtained from molecular simulation and confirmed the thermodynamic data.


Asunto(s)
Bencimidazoles , Carbamatos , Elastasa Pancreática , Espectrometría de Fluorescencia , Carbamatos/química , Carbamatos/metabolismo , Bencimidazoles/química , Elastasa Pancreática/metabolismo , Simulación del Acoplamiento Molecular , Espectrofotometría Ultravioleta , Animales , Termodinámica , Estabilidad de Enzimas/efectos de los fármacos , Unión Proteica , Simulación por Computador , Humanos , Fungicidas Industriales/química
7.
J Steroid Biochem Mol Biol ; 242: 106544, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38754521

RESUMEN

Sex steroid hormones such as estrogen estradiol (E2) and androgen dihydrotestosterone (DHT) are involved in the development of hormone-dependent cancers. Blockade of 17ß-hydroxysteroid dehydrogenase type 7 (17ß-HSD7), a member of the short chain dehydrogenase/reductase superfamily, is thought to decrease E2 levels while increasing those of DHT. Therefore, its unique double action makes this enzyme as an interesting drug target for treatment of breast cancer. The chemical synthesis, molecular characterization, and preliminary biological evaluation as 17ß-HSD7 inhibitors of novel carbamate derivatives 3 and 4 are described. Like previous 17ß-HSD7 inhibitors 1 and 2, compounds 3 and 4 bear a hydrophobic nonyl side chain at the C-17ß position of a 4-aza-5α-androstane nucleus, but compound 3 has an oxygen atom replacing the CH2 in the steroid A-ring C-2 position, while compound 4 has a C17-spiranic E-ring containing a carbamate function. They both inhibited the in vitro transformation of estrone (E1) into E2 by 17ß-HSD7, but the introduction of a (17 R)-spirocarbamate is preferable to replacing C-2 methylene with an oxygen atom since compound 4 (IC50 = 63 nM) is an inhibitor 14 times more powerful than compound 3 (IC50 = 900 nM). Furthermore, when compared to the reference inhibitor 1 (IC50 = 111 nM), the use of a C17-spiranic E-ring made it possible to introduce differently the hydrophobic nonyl side chain, without reducing the inhibitory activity.


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas , Inhibidores Enzimáticos , 17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Humanos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Estradiol/química , Estradiol/metabolismo , Estradiol/farmacología , Carbamatos/química , Carbamatos/farmacología , Carbamatos/síntesis química , Estrona/química , Estrona/farmacología , Estrona/síntesis química
8.
Mikrochim Acta ; 191(6): 348, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805077

RESUMEN

A novel aptamer-based sensor was developed using the signal amplification strategy of ring-opening metathesis polymerization (ROMP) and polyethyleneimine modified graphene oxide to achieve trace detection of carbendazim (CBZ). The dual identification of aptamer and antibody was used to avoid false positive results and improve the selectivity. Polyethyleneimine modified graphene oxide (GO-PEI), as a substrate material with excellent conductivity, was modified on the surface of a glassy carbon electrode (GCE) to increase the grafting amount of aptamer on the electrode surface. Moreover, a large number of cyclopentenyl ferrocene (CFc) was aggregated to form long polymer chains through ring-opening metathesis polymerization (ROMP), so as to significantly improve the detection sensitivity of the biosensor. The linear range of this sensor was 1 pg/mL-100 ng/mL with a detection limit as low as 7.80 fg/mL. The sensor exhibited excellent reproducibility and stability, and also achieved satisfactory results in actual sample detection. The design principle of such a sensor could provide innovative ideas for sensors in the detection of other types of targets.


Asunto(s)
Aptámeros de Nucleótidos , Bencimidazoles , Técnicas Biosensibles , Carbamatos , Técnicas Electroquímicas , Grafito , Límite de Detección , Polietileneimina , Polimerizacion , Grafito/química , Carbamatos/química , Carbamatos/análisis , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Polietileneimina/química , Técnicas Biosensibles/métodos , Bencimidazoles/química , Aptámeros de Nucleótidos/química , Electrodos , Reproducibilidad de los Resultados
9.
Angew Chem Int Ed Engl ; 63(30): e202405152, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38739413

RESUMEN

Biocatalysis provides an attractive approach to facilitate synthetic reactions in aqueous media. Motivated by the discovery of promiscuous aminolysis activity of esterases, we exploited the esterase from Pyrobaculum calidifontis VA1 (PestE) for the synthesis of carbamates from different aliphatic, aromatic, and arylaliphatic amines and a set of carbonates such as dimethyl-, dibenzyl-, or diallyl carbonate. Thus, aniline and benzylamine derivatives, aliphatic and even secondary amines could be efficiently converted into the corresponding benzyloxycarbonyl (Cbz)- or allyloxycarbonyl (Alloc)-protected products in bulk water, with (isolated) yields of up to 99 %.


Asunto(s)
Aciltransferasas , Carbamatos , Esterasas , Agua , Esterasas/metabolismo , Esterasas/química , Carbamatos/química , Carbamatos/metabolismo , Carbamatos/síntesis química , Agua/química , Aciltransferasas/metabolismo , Aciltransferasas/química , Biocatálisis , Estructura Molecular , Aminas/química , Aminas/metabolismo
10.
Macromol Rapid Commun ; 45(13): e2400022, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38704741

RESUMEN

The preparation of self-healing polyurethane elastomers (PUEs) incorporating dynamic bonds is of considerable practical significance. However, developing a PUE with outstanding mechanical properties and high self-healing efficiency poses a significant challenge. Herein, this work has successfully developed a series of self-healing PUEs with various outstanding properties through rational molecular design. These PUEs incorporate m-xylylene diisocyanate and reversible dimethylglyoxime as hard segment, along with polytetramethylene ether glycol as soft segment. A significant amount of dynamic oxime-carbamate and hydrogen bonds are formed in hard segment. The microphase separated structure of the PUEs enables them to be colorless with a transparency of >90%. Owing to the chemical composition and multiple dynamic interactions, the PUEs are endowed with ultra-high tensile strength of 34.5 MPa, satisfactory toughness of 53.9 MJ m-3, and great elastic recovery both at low and high strains. The movement of polymer molecular chains and the dynamic reversible interactions render a self-healing efficiency of 101% at 70 °C. In addition, this self-healing polyurethane could still maintain high mechanical properties after recycling. This study provides a design strategy for the preparation of a comprehensive polyurethane with superior overall performance, which holds wide application prospects in the fields of flexible displays and solar cells.


Asunto(s)
Carbamatos , Elastómeros , Enlace de Hidrógeno , Oximas , Poliuretanos , Resistencia a la Tracción , Poliuretanos/química , Oximas/química , Elastómeros/química , Carbamatos/química , Estructura Molecular , Elasticidad
11.
Sci Rep ; 14(1): 10293, 2024 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704412

RESUMEN

In this study, a sensitive and selective fluorescent chemosensor was developed for the determination of pirimicarb pesticide by adopting the surface molecular imprinting approach. The magnetic molecularly imprinted polymer (MIP) nanocomposite was prepared using pirimicarb as the template molecule, CuFe2O4 nanoparticles, and graphene quantum dots as a fluorophore (MIP-CuFe2O4/GQDs). It was then characterized using X-ray diffraction (XRD) technique, Fourier transforms infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), and transmission electron microscopy (TEM). The response surface methodology (RSM) was also employed to optimize and estimate the effective parameters of pirimicarb adsorption by this polymer. According to the experimental results, the average particle size and imprinting factor (IF) of this polymer are 53.61 nm and 2.48, respectively. Moreover, this polymer has an excellent ability to adsorb pirimicarb with a removal percentage of 99.92 at pH = 7.54, initial pirimicarb concentration = 10.17 mg/L, polymer dosage = 840 mg/L, and contact time = 6.15 min. The detection of pirimicarb was performed by fluorescence spectroscopy at a concentration range of 0-50 mg/L, and a sensitivity of 15.808 a.u/mg and a limit of detection of 1.79 mg/L were obtained. Real samples with RSD less than 2 were measured using this chemosensor. Besides, the proposed chemosensor demonstrated remarkable selectivity by checking some other insecticides with similar and different molecular structures to pirimicarb, such as diazinon, deltamethrin, and chlorpyrifos.


Asunto(s)
Plaguicidas , Pirimidinas , Plaguicidas/análisis , Carbamatos/análisis , Carbamatos/química , Puntos Cuánticos/química , Polímeros Impresos Molecularmente/química , Polímeros/química , Espectrometría de Fluorescencia/métodos , Grafito/química , Impresión Molecular/métodos , Adsorción , Límite de Detección , Espectroscopía Infrarroja por Transformada de Fourier , Nanocompuestos/química , Nanocompuestos/ultraestructura
12.
J Agric Food Chem ; 72(15): 8618-8631, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38569082

RESUMEN

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.


Asunto(s)
Isoflavonas , Profármacos , Animales , Ratas , Administración Oral , Aminoácidos/química , Disponibilidad Biológica , Carbamatos/química , Profármacos/química , Solubilidad , Agua
13.
Food Chem ; 450: 139260, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38626714

RESUMEN

High fluorescence intensity microspheres such as aggregation-induced emission fluorescence microspheres (AIEFM) have improved the sensitivity of lateral flow immunoassay (LFIA). The preparation of immune probes in LFIA usually adopts the chemical coupling strategy with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide for antibody coupling, which has the problems of low coupling efficiency, tedious coupling process, and poor repeatability. A biocompatible metal-phenolic network (MPN), which contains large amounts of phenols and galloyl groups, could easily, quickly, and stably couple with antibodies. Herein, we proposed a strategy based on MPN modification on ultrabright AIEFM surface as a novel label for the rapid detection of carbendazim. The limit of detection of AIEFM@MPN-LFIA was 0.019 ng/mL, which was 4.9 times lower than that of AIEFM-LFIA. In spiked samples, the average recoveries of AIEFM@MPN-LFIA ranged from 80% to 118% (coefficient of variation <13.45%). Therefore, AIEFM@MPN was a promising signal label that could improve the detection performance of LFIA.


Asunto(s)
Bencimidazoles , Carbamatos , Microesferas , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Bencimidazoles/química , Bencimidazoles/análisis , Carbamatos/análisis , Carbamatos/química , Fenoles/análisis , Fenoles/química , Límite de Detección , Contaminación de Alimentos/análisis , Fluorescencia , Metales/química , Colorantes Fluorescentes/química , Materiales Biocompatibles/química
14.
Chemistry ; 30(31): e202400883, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38556469

RESUMEN

We report on the syntheses of NeuAc and NeuGc-containing glycosides via the use of double carbonyl-protected N-acetyl sialyl donors. The 7-O,9-O-carbonyl protection of an N-acyl-5-N,4-O-carbonyl-protected sialyl donor markedly increased the α-selectivity during glycosylation, particularly when glycosylating the C-8 hydroxyl group of sialic acids. The N-acyl carbamates were selectively opened with ethanethiol under basic conditions to provide N-acyl amines. It is noteworthy that N-glycolyl carbamate was more reactive to nucleophiles by comparison with the N-acetyl carbamate due to the electron-withdrawing oxygen in the N-acyl group and however, allowed selective opening of the carbamates without the loss of N-glycolyl groups. To demonstrate the utility of the approach, we began by synthesizing α(2,3) and α(2,6) sialyl galactosides. Glycosylation of the hydroxy groups of galactosides at the C-6 position with the NeuAc and NeuGc donors provided the corresponding sialyl galactoses in good yields with excellent α-selectivity. However, glycosylation of the 2,3-diol galactosyl acceptor selectively provided Siaα(2,2)Gal. Next, we prepared a series of α(2,8) disialosides composed of NeuAc and NeuGc. Glycosylation of NeuGc and NeuAc acceptors at the C-8 hydroxyl group with NeuGc and NeuAc sialyl donors provided the corresponding α(2,8) disialosides, and no significant differences were detected in the reactivities of these acceptors.


Asunto(s)
Ácidos Siálicos , Glicosilación , Ácidos Siálicos/química , Ácidos Siálicos/síntesis química , Carbamatos/química , Carbamatos/síntesis química , Glicósidos/química , Glicósidos/síntesis química , Galactósidos/química , Galactósidos/síntesis química , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/síntesis química
15.
Macromol Rapid Commun ; 45(8): e2300699, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38224144

RESUMEN

Polymer dielectrics with high dielectric constant are urgently demanded for potential electrical and pulsed power applications. The design of polymers with side chains containing dipolar groups is considered an effective method for preparing materials with a high dielectric constant and low loss. This study synthesizes and comprehensively compare the dielectric properties of novel polyimides with side chains containing urea (BU-PI), carbamate (BC-PI), and sulfonyl (BS-PI) functional groups. The novel polyimides exhibit relatively high dielectric constant and low dielectric loss values due to the enhanced orientational polarization and suppressed dipole-dipole interactions of dipolar groups. In particular, BU-PI containing urea pendant groups presents the highest dielectric constant of 6.14 and reasonably low dielectric loss value of 0.0097. The strong γ transitions with low activation energies derived from dielectric spectroscopy measurements have been further evaluated to demonstrate the enhanced free rotational motion of urea pendant dipoles. In energy storage applications, BU-PI achieves a discharged energy density of 6.92 J cm-3 and a charge-discharge efficiency above 83% at 500 MV m-1. This study demonstrates that urea group, as dipolar pendant group, can provide polymers with better dielectric properties than the most commonly used sulfonyl groups.


Asunto(s)
Polímeros , Urea , Polímeros/química , Urea/química , Imidas/química , Estructura Molecular , Carbamatos/química , Espectroscopía Dieléctrica
16.
Inorg Chem ; 63(2): 1225-1235, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38163760

RESUMEN

A multifunctional single-atom nanozyme, denoted as 3D Ni,N-codoped porous carbon (Ni-NPC), was devised that exhibits remarkable adsorption capabilities and a repertoire of enzyme mimetic functions (oxidase- and peroxidase-like). These attributes stem from the distinctive mesoporous thin-shell structure and well-dispersed Ni sites. The efficient adsorption capacity of Ni-NPC was assessed with respect to three carbamate pesticides (CMPs): metolcarb, carbaryl, and isoprocarb. Moreover, a colorimetric detection method for CMP was established based on its robust peroxidase-like catalytic activity and sequential catalytic interactions with acetylcholinesterase. Furthermore, a portable colorimetric sensor based on a hydrogel sphere integrated with a smartphone platform was devised. This sensor enables rapid, on-site, and quantitative assessment of CMP, boasting an extraordinarily low detection limit of 1.5 ng mL-1. Notably, this sensor was successfully applied to the analysis of CMP levels in lake water and vegetable samples (pakchoi and rape), propelling the progress of real-time detection technologies in food and environment monitoring.


Asunto(s)
Plaguicidas , Teléfono Inteligente , Acetilcolinesterasa , Plaguicidas/análisis , Carbamatos/química , Peroxidasa , Peroxidasas , Colorimetría
17.
Bioorg Chem ; 143: 106977, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38064805

RESUMEN

It is reported that panaxadiol has neuroprotective effects. Previous studies have found that compound with carbamate structure introduced at the 3-OH position of 20 (R) -panaxadiol showed the most effective neuroprotective activity with an EC50 of 13.17 µM. Therefore, we designed and synthesized a series of ginseng diol carbamate derivatives with ginseng diol as the lead compound, and tested their anti-AD activity. It was found that the protective effect of compound Q4 on adrenal pheochromocytoma was 80.6 ±â€¯10.85 % (15 µM), and the EC50 was 4.32 µM. According to the ELISA results, Q4 reduced the expression of Aß25-35 by decreasing ß-secretase production. Molecular docking studies revealed that the binding affinity of Q4 to ß-secretase was -49.67 kcal/mol, indicating a strong binding affinity of Q4 to ß-secretase. Western blotting showed that compound Q4 decreased IL-1ß levels, which may contribute to its anti-inflammatory effect. Furthermore, compound Q4 exhibits anti-AD activities by reducing abnormal phosphorylation of tau protein and activation of the mitogen activated protein kinase pathway. The learning and memory deficits in mice treated with Q4in vivo were significantly alleviated. Therefore, Q4 may be a promising multifunctional drug for the treatment of AD, providing a new way for anti-AD drugs.


Asunto(s)
Enfermedad de Alzheimer , Ginsenósidos , Fármacos Neuroprotectores , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Simulación del Acoplamiento Molecular , Carbamatos/química , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico
18.
Bioconjug Chem ; 34(10): 1835-1850, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37788373

RESUMEN

Antibody-drug conjugates consist of potent small-molecule payloads linked to a targeting antibody. Payloads must possess a viable functional group by which a linker for conjugation can be attached. Linker-attachment options remain limited for the connection to payloads via hydroxyl groups. A releasing group based on 2-aminopyridine was developed to enable stable attachment of para-aminobenzyl carbamate (PABC) linkers to the C21-hydroxyl group of budesonide, a glucocorticoid receptor agonist. Payload release involves a cascade of two self-immolative events that are initiated by the protease-mediated cleavage of the dipeptide-PABC bond. Budesonide release rates were determined for a series of payload-linker intermediates in buffered solution at pH 7.4 and 5.4, leading to the identification of 2-aminopyridine as the preferred releasing group. Addition of a poly(ethylene glycol) group improved linker hydrophilicity, thereby providing CD19-budesonide ADCs with suitable properties. ADC23 demonstrated targeted delivery of budesonide to CD19-expressing cells and inhibited B-cell activation in mice.


Asunto(s)
Inmunoconjugados , Ratones , Animales , Inmunoconjugados/química , Carbamatos/química , Budesonida
19.
Anal Sci ; 39(7): 1129-1142, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37000321

RESUMEN

In the present work, a potential solid-phase extraction (SPE) material based on graphene anchored with platinum nanoparticles (Pt-Graphene) was prepared and characterized by scanning electron micrographs and transmission electron micrograph. The carbamates residues in fish were enriched by SPE filled with Pt-Graphene and detected by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The proposed extraction protocol exhibited satisfactory recoveries (76.5-115.6%), low limit of quantitation values in µg kg-1 level, and good precision for the studied ten carbamates. These results demonstrated the feasibility of the proposed protocol. The developed Pt-Graphene nanoparticles showed excellent performance for extracting analytes at trace levels, indicating that it could be used as a potential SPE sorbent in food residue analysis.


Asunto(s)
Grafito , Nanopartículas del Metal , Plaguicidas , Animales , Cromatografía Liquida/métodos , Grafito/química , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Nanopartículas del Metal/análisis , Platino (Metal) , Plaguicidas/análisis , Extracción en Fase Sólida/métodos , Carbamatos/análisis , Carbamatos/química
20.
Sci Rep ; 13(1): 1673, 2023 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-36717660

RESUMEN

New cellulose carbamates and cellulose acetate carbamates were prepared by classical addition reaction of isocyanates with alcohols. A Telomerization technique was used to make the grafted molecules strongly anchored and more hydrophobic. These molecules were grafted into cellulose and CA chains, respectively. The structures of the synthesized derivatives were confirmed using Nuclear Magnetic Resonance Spectroscopy, Fourier Transform Infrared and Thermogravimetric Analysis, and their solubility phenomenon was also established, and the carbamate derivatives showed better solubility compared to cellulose. Their ability to biodegrade was investigated, and it was concluded that Cell-P1 and CA-P1 derivatives are more biodegradable than the other samples. These results suggest that the resulting compounds can be used effectively in many useful industrial fields, for instance, eco-friendly food packaging, domains that use materials that are environmentally friendly and sustainable and the development of green chemistry.


Asunto(s)
Carbamatos , Celulosa , Biodegradación Ambiental , Solubilidad , Celulosa/química , Carbamatos/química , Polímeros , Espectroscopía Infrarroja por Transformada de Fourier
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