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1.
Molecules ; 29(13)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38998932

RESUMO

Microbial contamination has profoundly impacted human health, and the effective eradication of widespread microbial issues is essential for addressing serious hygiene concerns. Taking polystyrene (PS) membrane as an example, we herein developed report a robust strategy for the in situ preparation of chlorine-regenerable antimicrobial polymer molecular sieve membranes through combining post-crosslinking and nucleophilic substitution reaction. The cross-linking PS membranes underwent a reaction with 5,5-dimethylhydantoin (DMH), leading to the formation of polymeric N-halamine precursors (PS-DMH). These hydantoinyl groups within PS-DMH were then efficiently converted into biocidal N-halamine structures (PS-DMH-Cl) via a simple chlorination process. ATR-FTIR and XPS spectra were recorded to confirm the chemical composition of the as-prepared PS-DMH-Cl membranes. SEM analyses revealed that the chlorinated PS-DMH-Cl membranes displayed a rough surface with a multitude of humps. The effect of chlorination temperature and time on the oxidative chlorine content in the PS-DMH-Cl membranes was systematically studied. The antimicrobial assays demonstrated that the PS-DMH-Cl membranes could achieve a 6-log inactivation of E. coli and S. aureus within just 4 min of contact time. Additionally, the resulting PS-DMH-Cl membranes exhibited excellent stability and regenerability of the oxidative chlorine content.


Assuntos
Cloro , Escherichia coli , Membranas Artificiais , Staphylococcus aureus , Cloro/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Halogenação , Polímeros/química , Poliestirenos/química , Hidantoínas/química , Hidantoínas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Aminas
2.
Org Biomol Chem ; 22(28): 5843-5849, 2024 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-38957899

RESUMO

Phosphatidic acid and phosphatidylserine are anionic phospholipids with emerging signalling roles in cells. Determination of how phosphatidic acid and phosphatidylserine change location and quantity in cells over time requires selective fluorescent sensors that can distinguish these two anionic phospholipids. However, the design of such synthetic sensors that can selectively bind and respond to a single phospholipid within the complex membrane milieu remains challenging. In this work, we present a simple and robust strategy to control the selectivity of synthetic sensors for phosphatidic acid and phosphatidylserine. By changing the coordination metal of a dipicolylamine (DPA) ligand from Zn(II) to Ni(II) on the same synthetic sensor with a peptide backbone, we achieve a complete switch in selectivity from phosphatidic acid to phosphatidylserine in model lipid membranes. Furthermore, this strategy was largely unaffected by the choice and the position of the fluorophores. We envision that this strategy will provide a platform for the rational design of targeted synthetic phospholipid sensors to probe plasma and intracellular membranes.


Assuntos
Corantes Fluorescentes , Ácidos Fosfatídicos , Fosfatidilserinas , Ácidos Picolínicos , Zinco , Ácidos Fosfatídicos/química , Fosfatidilserinas/química , Ácidos Picolínicos/química , Corantes Fluorescentes/química , Zinco/química , Níquel/química , Cátions/química , Fosfolipídeos/química , Aminas/química , Estrutura Molecular
3.
Chem Commun (Camb) ; 60(59): 7638-7641, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38963238

RESUMO

The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.


Assuntos
DNA , Compostos Heterocíclicos , Isotiocianatos , Isotiocianatos/química , DNA/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/síntese química , Estrutura Molecular , Aminas/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/síntese química
4.
Dalton Trans ; 53(29): 12261-12280, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38980002

RESUMO

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn2(L1)2](ClO4)2·MeOH (1), [Zn2(L2)2](ClO4)2 (2), and four mononuclear [Zn(L3)(H2O)]·MeOH (3), [Zn(L4)] (4), [Zn(L5)] (5) and [Zn(L6)] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC50 values for complex 6 ranging from 2.4 to 4.5 µM), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC50 ≈ 16.3-19.5 µM) over MRC-5 ones (with IC50 >50 µM for 1, 2 and 4, and with IC50 >25 µM for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.


Assuntos
Aminas , Antineoplásicos , Apoptose , Proliferação de Células , Complexos de Coordenação , Zinco , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Zinco/química , Zinco/farmacologia , Proliferação de Células/efeitos dos fármacos , Aminas/química , Aminas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Espécies Reativas de Oxigênio/metabolismo , Estrutura Molecular , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Fenóis/síntese química , Relação Estrutura-Atividade
5.
Clin Exp Dent Res ; 10(4): e874, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39023214

RESUMO

OBJECTIVES: Reflecting the need for an effective support for the daily oral hygiene routine of patients experiencing (symptoms of) gum inflammation, a new mouthwash has been developed containing an amine + zinc lactate + fluoride system. The in vitro efficacy of this product was assessed using traditional laboratory methods, as well as novel experimentation. MATERIALS AND METHODS: This mouthwash has been evaluated in a series of laboratory tests including two short interval kill tests (SIKTs), a 12-h (longer term) biofilm regrowth assay, a plaque glycolysis assay, and an aerobic, repeated exposure biofilm model, as well as tests for soft tissue uptake and LPS neutralization. RESULTS: Several laboratory studies demonstrate that a mouthwash containing an amine + zinc lactate + fluoride system provides short-term and long-term antibacterial activity. While the immediate efficacy of this formula has been shown to be driven by the presence of the amine, zinc lactate provides a long-term antibacterial effect, as well as is able to inhibit bacterial metabolism. CONCLUSIONS: This research provides the basis for understanding the mode of action of this new mouthwash formulation and explains the previously observed clinical efficacy of this formula against plaque and gingivitis.


Assuntos
Antibacterianos , Biofilmes , Placa Dentária , Fluoretos , Antissépticos Bucais , Antissépticos Bucais/farmacologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Humanos , Fluoretos/farmacologia , Placa Dentária/microbiologia , Placa Dentária/tratamento farmacológico , Lactatos/farmacologia , Aminas/farmacologia , Aminas/química , Gengivite/tratamento farmacológico , Gengivite/microbiologia , Gengivite/prevenção & controle , Compostos de Zinco/farmacologia
6.
J Am Chem Soc ; 146(28): 19160-19167, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38958264

RESUMO

Boronic acids and esters are highly regarded for their safety, unique reactivity, and versatility in synthesizing a wide range of small molecules, bioconjugates, and materials. They are not exploited in biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon-boron bonds are rare. We wish to combine the advantages of boronic acids and esters for molecular assembly with biocatalysis, which offers the potential for unsurpassed selectivity and efficiency. Here, we introduce an engineered protoglobin nitrene transferase that catalyzes the new-to-nature amination of boronic acids using hydroxylamine. Initially targeting aryl boronic acids, we show that the engineered enzyme can produce a wide array of anilines with high yields and total turnover numbers (up to 99% yield and >4000 TTN), with water and boric acid as the only byproducts. We also demonstrate that the enzyme is effective with bench-stable boronic esters, which hydrolyze in situ to their corresponding boronic acids. Exploring the enzyme's capacity for enantioselective catalysis, we found that a racemic alkyl boronic ester affords an enantioenriched alkyl amine, a transformation not achieved with chemocatalysts. The formation of an exclusively unrearranged product during the amination of a boronic ester radical clock and the reaction's stereospecificity support a two-electron process akin to a 1,2-metallate shift mechanism. The developed transformation enables new biocatalytic routes for synthesizing chiral amines.


Assuntos
Aminas , Biocatálise , Ácidos Borônicos , Ácidos Borônicos/química , Ácidos Borônicos/metabolismo , Aminas/química , Aminas/metabolismo , Estereoisomerismo , Aminação , Estrutura Molecular
7.
Int J Biol Macromol ; 273(Pt 1): 132783, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38825285

RESUMO

In this study, a brand-new, easy, and environmentally friendly approach for chemically functionalizing 2,2,6,6-tetramethylpiperidinyloxyl radical (TEMPO)-oxidized cellulose nanofiber (TOCNF) to produce modified cellulose nanofiber (octadecylamine-citric acid-CNF) was proposed. Effects of octadecylamine (ODA)/TOCNF mass ratio on the chemical structure, morphology, surface hydrophobicity and oleophobicity were studied. According to Fourier transform infrared spectroscopy (FTIR) analysis, ODA was successfully grafted onto the TOCNF by simple citric acid (CA) esterification and amidation reactions. Scanning electron microscopy (SEM) showed that a new rough structure was formed on the ODA-CA-CNF surface. The water contact angle (WCA) and the castor oil contact angle (OCA) of the ODA-CA-CNF reached 139.6° and 130.6°, respectively. The high-grafting-amount ODA-CA-CNF was sprayed onto paper, and the OCA reached 118.4°, which indicated good oil-resistance performance. The low-grafting-amount ODA-CNF was applied in a pH-responsive indicator film, exhibiting a colour change in response to the pH level, which can be applied in smart food packaging. The ODA-CA-CNF with excellent water/oil-resistance properties and fluorine-free properties can replace petrochemical materials and can be used in the fields of fluorine-free oil-proof paper.


Assuntos
Celulose , Óxidos N-Cíclicos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Nanofibras/química , Celulose/química , Óxidos N-Cíclicos/química , Aminas/química , Ácido Cítrico/química , Água/química , Espectroscopia de Infravermelho com Transformada de Fourier , Flúor/química , Propriedades de Superfície
8.
Int J Biol Macromol ; 273(Pt 1): 133118, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38871106

RESUMO

Developing carbon quantum dots (CQDs) from bio-waste lignin for effectively detecting Cu2+ is of great significance for promoting the value-added utilization of lignin resources. However, the limited amount of surface-active groups and low quantum yield of lignin-based CQDs hinder their application in this regard. Herein, bio-waste lignin was converted into value-added amine functionalized CQDs using a facile two-step hydrothermal approach. The as-synthesized CQDs modified with amino groups exhibit bright green fluorescence, abundant surface functional groups, high water solubility and uniform particle size (3.9 nm). Systematic analysis demonstrates that the rich NH2 groups (~12.3 %) on the CQDs backbone improve their fluorescence properties (quantum yield increased from 3.4 % to 21.1 %) and specific detection ability for Cu2+. The developed NH2-CQDs serve as an efficient fluorescent probe, displaying high sensitivity and selectivity towards Cu2+ in aqueous system, with a detection limit of 2.42 µmol/L, which is lower than the maximum permitted amount of Cu2+ in drinking water (20 µmol/L). The detection mechanism of NH2-CQDs for Cu2+ is attributed to the synergy of static quenching and photo-induced electron transfer. This study provides a valuable reference for the synthesis of high-quality fluorescent CQDs from lignin resources and the effective detection of trace Cu2+ in aquatic environments.


Assuntos
Aminas , Carbono , Cobre , Lignina , Pontos Quânticos , Pontos Quânticos/química , Cobre/análise , Cobre/química , Lignina/química , Carbono/química , Aminas/química , Água/química , Poluentes Químicos da Água/análise , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Limite de Detecção
9.
Food Res Int ; 190: 114633, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945584

RESUMO

The Frankfurter sausages smoked with beech, oak, and alder, respectively, were used to clarify the underlying impact of the smoke chemical composition on the levels of heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs). The result indicated that different wood types significantly affected the profiles of target substances in food matrices. The beech-smoked samples had lower contents of total free HAs (5.98-6.80 ng/g dry-weight-DW), PAH4 (3.31-3.83 ng/g DW), and PAH8 (10.0-10.8 ng/g DW), whereas the alder pyrolysis usually led to higher hazardous residues (8.26-9.19 ng/g DW of total free HAs, 4.24-6.60 ng/g DW of PAH4 and 14.1-23.3 ng/g DW of PAH8). In addition, the differences in smoke chemical composition were attributed to the different proportions of 15 key identified substances. Among them, two aldehydes (5-methyl-furfural & furfural) and two phenols (phenol & 5-hydroxymaltol) may have synergistic or competitive inhibitory effects on the formation of HAs and PAHs in smoked meat products.


Assuntos
Aminas , Produtos da Carne , Hidrocarbonetos Policíclicos Aromáticos , Fumaça , Madeira , Hidrocarbonetos Policíclicos Aromáticos/análise , Produtos da Carne/análise , Fumaça/análise , Madeira/química , Aminas/análise , Compostos Heterocíclicos/análise , Contaminação de Alimentos/análise , Animais
10.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38928184

RESUMO

Simple and efficient sample pretreatment methods are important for analysis and detection of chemical warfare agents (CWAs) in environmental and biological samples. Despite many commercial materials or reagents that have been already applied in sample preparation, such as SPE columns, few materials with specificity have been utilized for purification or enrichment. In this study, ionic magnetic mesoporous nanomaterials such as poly(4-VB)@M-MSNs (magnetic mesoporous silicon nanoparticles modified by 4-vinyl benzene sulfonic acid) and Co2+@M-MSNs (magnetic mesoporous silicon nanoparticles modified by cobalt ions) with high absorptivity for ethanol amines (EAs, nitrogen mustard degradation products) and cyanide were successfully synthesized. The special nanomaterials were obtained by modification of magnetic mesoporous particles prepared based on co-precipitation using -SO3H and Co2+. The materials were fully characterized in terms of their composition and structure. The results indicated that poly(4-VB)@M-MSNs or Co2+@M-MSNs had an unambiguous core-shell structure with a BET of 341.7 m2·g-1 and a saturation magnetization intensity of 60.66 emu·g-1 which indicated the good thermal stability. Poly(4-VB)@M-MSNs showed selective adsorption for EAs while the Co2+@M-MSNs were for cyanide, respectively. The adsorption capacity quickly reached the adsorption equilibrium within the 90 s. The saturated adsorption amounts were MDEA = 35.83 mg·g-1, EDEA = 35.00 mg·g-1, TEA = 17.90 mg·g-1 and CN-= 31.48 mg·g-1, respectively. Meanwhile, the adsorption capacities could be maintained at 50-70% after three adsorption-desorption cycles. The adsorption isotherms were confirmed as the Langmuir equation and the Freundlich equation, respectively, and the adsorption mechanism was determined by DFT calculation. The adsorbents were applied for enrichment of targets in actual samples, which showed great potential for the verification of chemical weapons and the destruction of toxic chemicals.


Assuntos
Aminas , Cianetos , Etanol , Cianetos/química , Cianetos/isolamento & purificação , Adsorção , Aminas/química , Etanol/química , Porosidade , Cobalto/química , Nanopartículas de Magnetita/química , Nanoestruturas/química
11.
Nat Commun ; 15(1): 5181, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890290

RESUMO

Peptide aldehydes are crucial biomolecules essential to various biological systems, driving a continuous demand for efficient synthesis methods. Herein, we develop a metal-free, facile, and biocompatible strategy for direct electrochemical synthesis of unnatural peptide aldehydes. This electro-oxidative approach enabled a step- and atom-economical ring-opening via C‒N bond cleavage, allowing for homoproline-specific peptide diversification and expansion of substrate scope to include amides, esters, and cyclic amines of various sizes. The remarkable efficacy of the electro-synthetic protocol set the stage for the efficient modification and assembly of linear and macrocyclic peptides using a concise synthetic sequence with racemization-free conditions. Moreover, the combination of experiments and density functional theory (DFT) calculations indicates that different N-acyl groups play a decisive role in the reaction activity.


Assuntos
Aldeídos , Aminas , Técnicas Eletroquímicas , Peptídeos , Aldeídos/química , Aminas/química , Peptídeos/química , Peptídeos/síntese química , Técnicas Eletroquímicas/métodos , Oxirredução , Carbono/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/síntese química , Teoria da Densidade Funcional
12.
Adv Food Nutr Res ; 110: 1-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38906585

RESUMO

Heterocyclic aromatic amines (HAAs) constitute a group of highly toxic organic compounds strongly associated with the onset of various types of cancer. This paper aims to serve as a valuable resource for food scientists working towards a better understanding of these compounds including formation, minimizing strategies, analysis, and toxicity as well as addressing existing gaps in the literature. Despite extensive research conducted on these compounds since their discovery, several aspects remain inadequately understood, necessitating further investigation. These include their formation pathways, toxic mechanisms, effective mitigation strategies, and specific health effects on humans. Nonetheless, recent research has yielded promising results, contributing significantly to our understanding of HAAs by proposing new potential formation pathways and innovative strategies for their reduction.


Assuntos
Aminas , Compostos Heterocíclicos , Humanos , Carcinógenos/toxicidade , Neoplasias
13.
Biochem Biophys Res Commun ; 724: 150217, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38865809

RESUMO

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.


Assuntos
Flavonas , Hiperalgesia , Neuralgia , Ratos Sprague-Dawley , Animais , Ratos , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Flavonas/farmacologia , Flavonas/uso terapêutico , Hiperalgesia/tratamento farmacológico , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Gabapentina/farmacologia , Gabapentina/uso terapêutico , Nociceptividade/efeitos dos fármacos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Feminino , Ácido gama-Aminobutírico/metabolismo , Aminas/farmacologia , Aminas/uso terapêutico , Nervo Isquiático/lesões , Nervo Isquiático/efeitos dos fármacos , Vulvodinia/tratamento farmacológico , Constrição , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico
14.
Nat Commun ; 15(1): 4933, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858403

RESUMO

Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.


Assuntos
Aminas , Aminas/metabolismo , Aminas/química , Especificidade por Substrato , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/química , Biologia Computacional/métodos , Biocatálise , Biodiversidade , Modelos Moleculares
15.
Sci Rep ; 14(1): 13362, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862754

RESUMO

The Increase in infections caused by resistant strains of Pseudomonas aeruginosa poses a formidable challenge to global healthcare systems. P. aeruginosa is capable of causing severe human infections across diverse anatomical sites, presenting considerable therapeutic obstacles due to its heightened drug resistance. Niosomal drug delivery systems offer enhanced pharmaceutical potential for loaded contents due to their desirable properties, mainly providing a controlled-release profile. This study aimed to formulate an optimized niosomal drug delivery system incorporating stearylamine (SA) to augment the anti-bacterial and anti-biofilm activities of quercetin (QCT) against both standard and clinical strains of P. aeruginosa. QCT-loaded niosome (QCT-niosome) and QCT-loaded SA- niosome (QCT-SA- niosome) were synthesized by the thin-film hydration technique, and their physicochemical characteristics were evaluated by field emission scanning electron microscopy (FE-SEM), zeta potential measurement, entrapment efficacy (EE%), and in vitro release profile. The anti-P. aeruginosa activity of synthesized niosomes was assessed using minimum inhibitory and bactericidal concentrations (MICs/MBCs) and compared with free QCT. Additionally, the minimum biofilm inhibitory and eradication concentrations (MBICs/MBECs) were carried out to analyze the ability of QCT-niosome and QCT-SA-niosome against P. aeruginosa biofilms. Furthermore, the cytotoxicity assay was conducted on the L929 mouse fibroblasts cell line to evaluate the biocompatibility of the formulated niosomes. FE-SEM analysis revealed that both synthesized niosomal formulations exhibited spherical morphology with different sizes (57.4 nm for QCT-niosome and 178.9 nm for QCT-SA-niosome). The EE% for cationic and standard niosomal formulations was reported at 75.9% and 59.6%, respectively. Both formulations showed an in vitro sustained-release profile, and QCT-SA-niosome exhibited greater stability during a 4-month storage time compared to QCT-niosome. Microbial experiments indicated that both prepared formulations had higher anti-bacterial and anti-biofilm activities than free QCT. Also, the QCT-SA-niosome exhibited greater reductions in MIC, MBC, MBIC, and MBEC values compared to the QCT-niosome at equivalent concentrations. This study supports the potential of QCT-niosome and QCT-SA-niosome as effective agents against P. aeruginosa infections, manifesting significant anti-bacterial and anti-biofilm efficacy alongside biocompatibility with L929 cell lines. Furthermore, our results suggest that optimized QCT-niosome with cationic lipids could efficiently target P. aeruginosa cells with negligible cytotoxic effect.


Assuntos
Antibacterianos , Biofilmes , Sistemas de Liberação de Medicamentos , Lipossomos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Quercetina , Pseudomonas aeruginosa/efeitos dos fármacos , Lipossomos/química , Quercetina/farmacologia , Quercetina/química , Quercetina/administração & dosagem , Animais , Biofilmes/efeitos dos fármacos , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Cátions/química , Humanos , Lipídeos/química , Linhagem Celular , Aminas
16.
Org Biomol Chem ; 22(25): 5087-5092, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38835316

RESUMO

We have devised a supported-amine-catalyzed efficient synthesis of spiro-thiazolone-tetrahydrothiophenes via a sulfa-Michael/aldol cascade approach. The catalyst demonstrated sustained efficacy over 21 cycles. These derivatives were found to exhibit excellent binding abilities with purified human serum albumin as indicated by both in silico and in vitro-based experiments.


Assuntos
Aminas , Tiofenos , Humanos , Catálise , Tiofenos/química , Tiofenos/síntese química , Aminas/química , Aminas/síntese química , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Ligação Proteica , Compostos de Espiro/química , Compostos de Espiro/síntese química , Estrutura Molecular , Tiazóis/química , Tiazóis/síntese química , Simulação de Acoplamento Molecular
17.
J Chem Inf Model ; 64(12): 4661-4672, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38860710

RESUMO

DNA-encoded library technology grants access to nearly infinite opportunities to explore the chemical structure space for drug discovery. Successful navigation depends on the design and synthesis of libraries with appropriate physicochemical properties (PCPs) and structural diversity while aligning with practical considerations. To this end, we analyze combinatorial library design constraints including the number of chemistry cycles, bond construction strategies, and building block (BB) class selection in pursuit of ideal library designs. We compare two-cycle library designs (amino acid + carboxylic acid, primary amine + carboxylic acid) in the context of PCPs and chemical space coverage, given different BB selection strategies and constraints. We find that broad availability of amines and acids is essential for enabling the widest exploration of chemical space. Surprisingly, cost is not a driving factor, and virtually, the same chemical space can be explored with "budget" BBs.


Assuntos
DNA , Bibliotecas de Moléculas Pequenas , DNA/química , Bibliotecas de Moléculas Pequenas/química , Descoberta de Drogas/métodos , Técnicas de Química Combinatória , Desenho de Fármacos , Aminas/química , Ácidos Carboxílicos/química , Biblioteca Gênica
18.
J Hazard Mater ; 475: 134843, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38870859

RESUMO

ß-Carboline heterocyclic amines (ß-CHAs), known for their synergistic neurotoxic and carcinogenic effects, are predominantly produced by humans through cigarette smoke and food and are found particularly in meats cooked at high temperatures. Few studies have explored the differences in the mechanisms of accumulation of ß-CHAs in smoked meat and meat processed at high temperatures. In this research, the concentration of ß-CHAs in smoked meats prepared using a variety of wood materials was measured using LCMS/MS. Additionally, key volatile organic compound markers associated with ß-CHAs accumulation in smoke were identified through GCMS and multivariate statistical analysis and subsequently confirmed in a chemical simulation system. Three types of strainers, each with a distinct aperture size, were used to assess the efficacy of particle filtration in reducing ß-CHAs levels in smoked meat. The findings indicated that smoke exposure indeed increases the ß-CHAs content of meat. However, only the strainer capable of filtering PM2.5-sized particles reduced the amount of ß-CHAs present compared to the control group. In contrast, strainers with larger pore sizes facilitated excessive accumulation of ß-CHAs. The presence of aldehydes such as 1 H-pyrrole-2-carboxaldehyde, 5-methylfurfural, benzaldehyde, furfural, and nonanal exhibited a positive correlation with the accumulation of ß-CHAs. Conversely, phenolic compounds, including 2-methoxy-4-vinylphenol, 2-methoxy-5-methylphenol, p-cresol, phenol, 2-methoxy-4-(1-propenyl)-, (Z)-, phenol, 3-ethyl-, and phenol, 4-ethyl-2-methoxy-, showed a negative correlation. Thus, filters made from chelated carbonyl trap materials both chemically and physically disrupt the buildup of ß-CHAs in smoked meats. The use of this approach will not only improve the quality of these products but will also contribute to decreasing the amount of inhalation pollutants released into the environment.


Assuntos
Carbolinas , Fumaça , Carbolinas/química , Fumaça/análise , Aminas/química , Aminas/análise , Animais , Carne/análise , Produtos da Carne/análise , Culinária , Madeira/química , Material Particulado/análise , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Compostos Heterocíclicos/análise
19.
Chemosphere ; 361: 142524, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38844103

RESUMO

Covalent Organic Frameworks (COF) having conjugated backbone are an interesting class of metal-free, visible light active, heterogeneous photocatalysts. Interestingly, synthesis of COF using continuous flow process has emerged as an efficient, alternative method when compared to the traditional batch process. Here, we demonstrate the possibility to engineer the physical properties and hence the adsorption and catalytic activities of a ß-ketoenamine COF by varying monomer flow rate and microreactor design during the continuous flow synthesis. Crystallinity of the COF increases on varying the monomer flow rate from 100 (S-100) to 500 (S-500) and up to 1000 µLmin-1 (S-1000), in an S-shaped microreactor, resulting in an enhanced surface area: 525, 722 and 1119 m2g-1 respectively. The photophysical properties of the COF are also found to vary significantly with the change in flow synthesis conditions. S-1000 is characterized by the highest adsorption of MB, due to its high surface area and accessible pores. On the other hand, S-500 shows the highest photocurrent, a low recombination of photogenerated charges and the lowest charge transfer resistance. Thus, S-500 is found to be the best photocatalyst for the removal of a model pollutant (methylene blue, MB). Further, enhanced photocatalytic removal of MB using S-500 could be achieved by performing the photocatalysis in continuous flow.


Assuntos
Estruturas Metalorgânicas , Catálise , Estruturas Metalorgânicas/química , Adsorção , Luz , Processos Fotoquímicos , Poluentes Químicos da Água/química , Aminas/química , Cetonas
20.
Eur J Pharm Biopharm ; 201: 114349, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38848782

RESUMO

Nanocarriers have demonstrated promising potential in the delivery of various anticancer drugs and in improving the efficiency of the treatment. In this study, silver nanoparticles (AgNPs) were green-synthesized using the extracts of different parts of the pomegranate plant, including the peel, flower petals, and calyx. To obtain the most efficient extract used for the green synthesis of AgNPs, all three types of synthesized nanoparticles were characterized. Then, (3-Aminopropyl) triethoxysilane-functionalized mesoporous silica nanoparticles (MSNs-APTES) decorated with AgNPs were fabricated via a one-pot green-synthesis method. AgNPs were directly coated on the surface of MSNs-APTES by adding pomegranate extract enriched with a source of reducing agent leading to converting the silver ion to AgNPs. The MSN-APTES-AgNPs (MSNs-AgNPs) have been thoroughly characterized using nanoparticle characterization techniques. In addition, DNA cleavage and hemolysis activities of the synthesized nanoparticles were analyzed, confirming the biocompatibility of synthesized nanoparticles. The Doxorubicin (DOX, as a breast/cervical anti-cancer drug) loading (42.8%) and release profiles were investigated via UV-visible spectroscopy. The fibroblast, breast cancer, and cervical cancer cells' viability against DOX-loaded nanoparticles were also studied. The results of this high drug loading, uniform shape, and small functionalized nanoparticles demonstrated its great potential for breast and cervical cancer management.


Assuntos
Neoplasias da Mama , Doxorrubicina , Nanopartículas Metálicas , Dióxido de Silício , Prata , Neoplasias do Colo do Útero , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Dióxido de Silício/química , Prata/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Nanopartículas Metálicas/química , Porosidade , Portadores de Fármacos/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Punica granatum/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Aminas/química , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células MCF-7 , Células HeLa , Animais , Liberação Controlada de Fármacos
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