RESUMEN

In this study, covalent organic frameworks (COFs) were grown in situ on magnetic nitrogen-doped graphene foam (MNGF), and the resulting composite of COFs-modified MNGF (MNC) was wrapped by molecularly imprinted polymers (MNC@MIPs) for specifically capturing SAs. A magnetic solid phase extraction (MSPE) method for SAs was established using MNC@MIPs with good magnetic responsiveness. The adsorption performance of MNC@MIPs was superior to that of non-molecularly imprinted polymers (MNC@NIPs), with shorter adsorption/desorption time and higher imprinting factors. A high-efficiency SAs analytical method was developed by fusing HPLC and MNC@MIPs-based MSPE. This approach provides excellent precision, a low detection limit, and wide linearity. By analyzing fish samples, the feasibility of the approach was confirmed, with SAs recoveries and relative standard deviations in spiked samples in the ranges of 77.2-112.7 % and 2.0-7.2 %, respectively. This study demonstrated the potential use of MNC@MIPs-based MSPE for efficient extraction and quantitation of trace hazards in food.

Asunto(s)

Peces , Contaminación de Alimentos , Estructuras Metalorgánicas , Polímeros Impresos Molecularmente , Extracción en Fase Sólida , Sulfonamidas , Extracción en Fase Sólida/métodos , Extracción en Fase Sólida/instrumentación , Animales , Polímeros Impresos Molecularmente/química , Adsorción , Contaminación de Alimentos/análisis , Estructuras Metalorgánicas/química , Sulfonamidas/aislamiento & purificación , Sulfonamidas/química , Sulfonamidas/análisis , Impresión Molecular , Polímeros/química

RESUMEN

BACKGROUND: Environmental reservoirs of antibiotic resistance pose a threat to human and animal health. Aquatic biofilms impacted by wastewater effluent (WW) are known environmental reservoirs for antibiotic resistance; however, the relative importance of biotic factors and abiotic factors from WW on the abundance of antibiotic resistance genes (ARGs) within aquatic biofilms remains unclear. Additionally, experimental evidence is limited within complex aquatic microbial communities as to whether genes bearing low sequence similarity to validated reference ARGs are functional as ARGs. RESULTS: To disentangle the effects of abiotic and biotic factors on ARG abundances, natural biofilms were previously grown in flume systems with different proportions of stream water and either ultrafiltered or non-ultrafiltered WW. In this study, we conducted deep shotgun metagenomic sequencing of 75 biofilm, stream, and WW samples from these flume systems and compared the taxonomic and functional microbiome and resistome composition. Statistical analysis revealed an alignment of the resistome and microbiome composition and a significant association with experimental treatment. Several ARG classes exhibited an increase in normalized metagenomic abundances in biofilms grown with increasing percentages of non-ultrafiltered WW. In contrast, sulfonamide and extended-spectrum beta-lactamase ARGs showed greater abundances in biofilms grown in ultrafiltered WW compared to non-ultrafiltered WW. Overall, our results pointed toward the dominance of biotic factors over abiotic factors in determining ARG abundances in WW-impacted stream biofilms and suggested gene family-specific mechanisms for ARGs that exhibited divergent abundance patterns. To investigate one of these specific ARG families experimentally, we biochemically characterized a new beta-lactamase from the Planctomycetota (Phycisphaeraceae). This beta-lactamase displayed activity in the cleavage of cephalosporin analog despite sharing a low sequence identity with known ARGs. CONCLUSIONS: This discovery of a functional planctomycete beta-lactamase ARG is noteworthy, not only because it was the first beta-lactamase to be biochemically characterized from this phylum, but also because it was not detected by standard homology-based ARG tools. In summary, this study conducted a metagenomic analysis of the relative importance of biotic and abiotic factors in the context of WW discharge and their impact on both known and new ARGs in aquatic biofilms. Video Abstract.

Asunto(s)

Biopelículas , Metagenómica , Ríos , Aguas Residuales , beta-Lactamasas , Biopelículas/efectos de los fármacos , Aguas Residuales/microbiología , beta-Lactamasas/genética , Ríos/microbiología , Microbiota/efectos de los fármacos , Bacterias/genética , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Antibacterianos/farmacología , Planctomycetales/genética , Planctomycetales/efectos de los fármacos , Metagenoma , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo

RESUMEN

BACKGROUND: Sulfonamide (SA) residues in food of animal origin possess a potential threat to human health and environment. However, due to the polar and ionic characteristics and trace level of SAs and the complexity of food matrices, direct measurement of SAs in these samples is still very difficult. Development of efficient sample pretreatment method for sensitive and selective extraction of trace SAs is of great significance and urgently desired. Therefore, rational design and synthesizing advanced and selective extractants is quite important. RESULTS: In this work, a novel phenazine-based microporous organic network (MON) named TEPM-DP is reasonably synthesized and employed as a packing material for selective solid phase extraction (SPE) and sensitive determination of four typical SAs in milk samples. Phenazine-based monomer with aromatic and heteroaromatic ring and numerous N atoms is chosen to construct TEPM-DP adsorbent to provide π-π, hydrogen bonding, hydrophobic, and electrostatic extraction sites for SAs. The proposed method owns wide linear ranges, low limits of detection, high enrichment factors, and good precisions and recoveries for SAs in complex milk samples. The recoveries of SAs on TEPM-DP are much higher than those of commercial C18 and activated carbon. The extraction mechanisms are also elucidated via FT-IR, XPS, and comparative experiments. SIGNIFICANCE: This work reports the first example of design and synthesizing phenazine-based MON in SPE via a simple and rapid solvothermal method. The results reveal the great prospects of TEPM-DP for enriching polar and ionic SAs in complex samples and uncover the potency of phenazine-based MON in sample pretreatment, which will promote the development of MON.

Asunto(s)

Leche , Fenazinas , Extracción en Fase Sólida , Sulfonamidas , Fenazinas/química , Leche/química , Animales , Sulfonamidas/análisis , Sulfonamidas/aislamiento & purificación , Extracción en Fase Sólida/métodos , Porosidad , Límite de Detección , Adsorción , Contaminación de Alimentos/análisis

RESUMEN

Synthetic sulfonamide anticancer drugs, including E7820, indisulam, tasisulam, and chloroquinoxaline sulfonamide, exhibit diverse mechanisms of action and therapeutic potential, functioning as molecular glue degraders. E7820 targets RBM39, affecting RNA splicing and angiogenesis by suppressing integrin α2. Phase I studies have demonstrated some stability in advanced solid malignancies; however, further efficacy studies are required. Indisulam causes G1 cell cycle arrest and delays the G1/S transition by modulating splicing through RBM39 degradation via DCAF15. Despite its limited initial efficacy, it shows promise in combination therapies, particularly for hematopoietic malignancies and gliomas. Tasisulam inhibits VEGF signaling, suppresses angiogenesis, and induces apoptosis. Although early trials indicated broad activity, safety concerns have halted its development. Chloroquinoxaline sulfonamide, initially investigated for cell cycle arrest and topoisomerase II inhibition, was discontinued owing to its limited efficacy and toxicity, despite promising initial results. Recent studies revealed the structural interaction of E7820 with DCAF15 and RBM39, although phase II trials on myeloid malignancies have shown limited efficacy. Indisulam is effective against glioblastoma and neuroblastoma, with potential synergy in combination therapies and metabolic disruption. Recent research on tasisulam reveals its potential in cancer therapy by targeting RBM39 degradation through DCAF15-mediated pathways. Understanding these mechanisms could lead to new treatments that affect alternative splicing and improve cancer therapies Overall, although these drugs exhibit promising mechanisms of action, further research is required to optimize their clinical efficacy and safety.

RESUMEN

The need for targeted pest control strategies has led to the development of juvenile hormone (JH) mimics that selectively disrupt the life cycles of harmful insect species. Present study focuses on the synthesis, characterization and evaluation of sulfonyl-acetohydrazide derivatives (H1-H8) as novel JH mimics on two different insect species, with an emphasis on their insect-specific action. The yellow fever mosquito, Aedes aegypti and cabbage leaf borer, Spodoptera litura, were selected for this investigation. Our results indicate that while these compounds exhibit negligible effects on the development of Aedes aegypti, they demonstrate a potent and specific action against Spodoptera litura. The sulfonyl-acetohydrazide derivatives induced significant developmental abnormalities and increased mortality rates in Spodoptera litura larvae, leading to a marked disruption in their life cycle. Additionally, Density Functional Theory methods were employed to elucidate the electronic structure and corelate the reactivity of the synthesized compounds with the insect growth regulating activity (IGR). The DNA-binding study of synthesized JH analogs has been carried out using UV-vis spectroscopy for toxicity assessment against biomolecule DNA. All the synthesized JH analogs (H1-H8) show IGR action and exhibit better reactivity and reduced toxicity as compared to the commercial in use IGR, pyriproxyfen.

RESUMEN

The thermal-responsive magnetic molecularly imprinted polymer (TrMMIP) sorbent was synthesized by surface imprinting method, and then used for magnetic solid-phase extraction (MSPE) and subsequent integrated into the ion source for elution and ionization. The shrinking-strength states change of the thermal-responsive polymer chain on TrMMIP alters the wettability of the sorbent when the working temperature crosses the lower critical solution temperature (LCST) of the polymer, and thus affects its behavior of in the extraction and clean-up process. The targeted analytes could be effectively extracted due to the high selectivity of MIPs and well dispersibility of polymer chain under the open state. Additionally, a hydrophilic polymer chain wrapped on the sorbent surface further protected target substances from co-elution during cleanup. Analytical methods for sulfonamide antibiotics (SAs) detection in complex food samples (milk, honey, fish) were developed, demonstrating potential for rapid and sensitive SAs analysis in diverse food and biological samples.

Asunto(s)

Antibacterianos , Contaminación de Alimentos , Miel , Interacciones Hidrofóbicas e Hidrofílicas , Leche , Polímeros Impresos Molecularmente , Extracción en Fase Sólida , Sulfonamidas , Contaminación de Alimentos/análisis , Antibacterianos/análisis , Antibacterianos/química , Polímeros Impresos Molecularmente/química , Leche/química , Extracción en Fase Sólida/instrumentación , Extracción en Fase Sólida/métodos , Animales , Miel/análisis , Sulfonamidas/química , Sulfonamidas/análisis , Impresión Molecular , Peces , Polímeros/química , Adsorción , Espectrometría de Masas

RESUMEN

Achieving consensus about the rhizosphere effect on soil antibiotic resistomes is challenging due to the variability in antibiotic concentrations, sources, and the elusory underlying mechanisms. Here, we characterized the antibiotic resistomes in both the rhizosphere and bulk soils of soybean plants grown in environments with varying levels of antibiotic contamination, using sulfamethoxazole (SMX) as a model compound. We also investigated the factors influencing resistome profiles. Soybean cultivation altered the structure of antibiotic-resistant genes (ARGs) and increased their absolute abundance. However, the rhizosphere effect on the relative abundance of ARGs was dependent on SMX concentrations. At low SMX levels, the rhizosphere effect was characterized by the inhibition of antibiotic-resistant bacteria (ARBs) and the promotion of sensitive bacteria. In contrast, at high SMX levels, the rhizosphere promoted the growth of ARBs and facilitated horizontal gene transfer of ARGs. This novel mechanism provides new insights into accurately assessing the rhizosphere effect on soil antibiotic resistomes.

Asunto(s)

Antibacterianos , Bacterias , Glycine max , Rizosfera , Microbiología del Suelo , Sulfametoxazol , Sulfametoxazol/farmacología , Sulfametoxazol/metabolismo , Glycine max/crecimiento & desarrollo , Glycine max/metabolismo , Glycine max/química , Glycine max/microbiología , Antibacterianos/farmacología , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Suelo/química , Farmacorresistencia Bacteriana/genética , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Raíces de Plantas/química , Raíces de Plantas/crecimiento & desarrollo , Contaminantes del Suelo/metabolismo

RESUMEN

In the search of new cymantrenyl- and ferrocenyl-sulfonamides as potencial inhibitors of human carbonic anhydrases (hCAs), four compounds based on N-ethyl or N-methyl benzenesulfonamide units have been obtained. These cymantrenyl (1a-b) and ferrocenyl (2a-b) derivatives were prepared by the reaction between aminobenzene sulfonamides ([NH2-(CH2)n-(C6H4)-SO2-NH2)], where n = 1, 2) with cymantrenyl sulfonyl chloride (P1) or ferrocenyl sulfonyl chloride (P2), respectively. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. In the solid state, the molecular structures of compounds 1a, 1b, and 2b were determined by single-crystal X-ray diffraction. Biological evaluation as carbonic anhydrases inhibitors were carried out and showed derivatives 1b y 2b present a higher inhibition than the drug control for the Human Carbonic Anhydrase (hCA) II and IX isoforms (KI = 7.3 nM and 5.8 nM, respectively) and behave as selective inhibition for hCA II isoform. Finally, the docking studies confirmed they share the same binding site and interactions as the known inhibitors acetazolamide (AAZ) and agree with biological studies.

Asunto(s)

Inhibidores de Anhidrasa Carbónica , Anhidrasas Carbónicas , Simulación del Acoplamiento Molecular , Sulfonamidas , Humanos , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Anhidrasas Carbónicas/metabolismo , Anhidrasas Carbónicas/química , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/metabolismo , Anhidrasa Carbónica II/química , Anhidrasa Carbónica IX/antagonistas & inhibidores , Anhidrasa Carbónica IX/metabolismo , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/química , Anhidrasa Carbónica I/antagonistas & inhibidores , Anhidrasa Carbónica I/metabolismo , Bencenosulfonamidas , Compuestos Organometálicos/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/farmacología , Cristalografía por Rayos X

RESUMEN

Sulfonamides are not only widely applied in clinics but also highly valued in animal husbandry. Recently, it has become common for sulfonamide residues to exceed the standard limits in food, which can affect human health. Current regulations limit these residues. Therefore, we constructed a new limit test method to rapidly determine the levels of sulfonamide residues. Six sulfonamides were detected using the latest method called TLC-SERS, namely, sulfamethasone (A), sulfamethazine (B), sulfadoxine (C), sulfamethoxydiazine (D), sulfamethoxazole (E), and sulfathiazole (F). The optimal conditions for SERS detection were investigated for these six drugs, and the separation effects of different TLC spreaders on them were compared. Then, we successfully established a separation system using dichloromethane-methanol-ammonia in a ratio of 5:1:0.25 (v/v/v), which provided good separation effects on the six drugs. The residues were preliminarily separated via TLC. A silver sol solution was added to the spot on the silica gel G plate at the corresponding specific shift values, and SERS detection was performed. The sample solution was placed on the spot under a 532 nm laser, and the SERS spectrum was collected and analyzed for the six sulfonamides. The results showed obvious variations in the SERS spectrum among the six sulfonamides, with the LODs being 12.5, 6.4, 6.3, 7.1, 18.8, and 6.2 ng/mL from A to F, respectively, and an RSD of <3.0%. Within 48 h, the SERS signal for each sulfonamide drug was kept stable, with an RSD of <3.0%. The detection results of 20 samples using the TLC-SERS method were consistent with those obtained by UPLC-MS/MS. The established TLC-SERS method is simple and fast, providing a useful reference for the rapid detection of residue limits in food.

Asunto(s)

Espectrometría Raman , Sulfonamidas , Sulfonamidas/análisis , Cromatografía en Capa Delgada/métodos , Espectrometría Raman/métodos , Contaminación de Alimentos/análisis , Análisis de los Alimentos/métodos , Residuos de Medicamentos/análisis , Límite de Detección , Animales

RESUMEN

Organofluorine compounds have consistently demonstrated practical applications in the life sciences due to the fascinating properties imparted by the fluorine substituents. In recent years, significant advancements have been made in the synthesis of N-fluoroalkyl carbonyl and sulfonyl compounds. This review offers a current overview of the various synthetic routes for N-fluoroalkyl amides/sulfonamides and their transformation to new unexplored N-fluoroalkyl carbonyl/sulfonyl derivatives, categorized into three parts based on the different fluoroalkyl groups.

RESUMEN

The widespread existence and persistence of antibiotics in the aquatic environment, and their extensive ecological risks, have attracted considerable attention. The objective of this study was to evaluate the occurrence and distribution of 25 antibiotics in environmental and biological samples from Poyang Lake Basin in China. SPE-HPLC-MS/MS was used to quantify the concentrations in different matrices. The total concentrations ranged from 144 to 933 ng/L in the water and 346 to 1154 ng/g in the sediment. In the spatial distribution analysis of this basin, the concentrations in the Ganjiang River were generally higher than those in Poyang Lake. The seasonal distribution in the wet and dry seasons showed comparatively higher concentrations during the dry season than the wet season. Additionally, antibiotics were found in various hydrophytes and animals, and the bioconcentration factor values followed the order: emergent plants > floating plants > submerged plants and benthic organisms > ducks > fish. Moreover, correlations among different matrices showed that antibiotics in viviparid snails were significantly positively correlated with those in ducks, and negatively correlated with those in carps, indicating the transmission relationship through the food chain. The results showed the trophic transfer of antibiotics in the food web and their potential environmental impacts on Poyang Lake Basin need constant attention.

RESUMEN

Protecting human health and ensuring food security require the swift and accurate detection of sulfonamides (SAs) residues in foods. Herein, we proposed an Eu-postfunctionalized bimetallic porphyrin metal-organic framework (PCN-221(Zr/Ce)@Eu-DPA-H4btec) synthesized solvothermally for fluorescence sensing. The PCN-221(Zr/Ce)@Eu-DPA-H4btec fluorescent sensor demonstrated excellent stability and high selectivity to SAs, and the detection limits of sulfamethazine (SM2), sulfamerazine (SMR), and sulfamethoxydiazine (SMD) were as low as 56 nmol/L, 45 nmol/L, and 56 nmol/L, respectively. The PCN-221(Zr/Ce)@Eu-DPA-H4btec fluorescent sensor was successfully applied for the detection of SM2, SMR, and SMD in real pork and milk samples, with satisfactory recoveries (81.2-118.3%) and high precisions (RSDs <8.2, n = 3). Combining the optical properties of the nanohybrids, PCN-221(Zr/Ce)@Eu-DPA-H4btec integrated fluorescent hydrogels were innovatively prepared for visual sensing of SM2, SMR, and SMD. This study provides an uncomplicated and sensitive method for SAs detection in food matrices.

Asunto(s)

Europio , Contaminación de Alimentos , Hidrogeles , Estructuras Metalorgánicas , Leche , Porfirinas , Espectrometría de Fluorescencia , Sulfonamidas , Estructuras Metalorgánicas/química , Contaminación de Alimentos/análisis , Europio/química , Leche/química , Animales , Sulfonamidas/química , Sulfonamidas/análisis , Porfirinas/química , Hidrogeles/química , Porcinos , Fluorescencia , Límite de Detección , Colorantes Fluorescentes/química

RESUMEN

Sulfonamides are one of the oldest groups of antibacterial agents with a broad-spectrum, used as first line treatment in bacterial infections. Their widespread use produced a selective pressure on bacteria, as observed by the high incidence of sulfonamides resistance mainly in Gram negative bacteria isolated from animals. In this research, the presence of sulfonamide resistance genes (sul1, sul2, sul3, and sul4) in phenotypically resistant Escherichia coli isolates has been studied. These genes were amplified in isolates recovered from five animal species, with different interactions to humans: cattle, swine, poultry as livestock, and dogs and cats as companion animals. Isolates were collected according to their phenotypic resistance, and the magnetic bead-based Luminex technology was applied to simultaneously detect sul target genes. The frequency of sul genes was highest in swine, among livestock isolates. The sul1 and sul2 were the most frequently sulfonamide resistance genes detected in all phenotypically resistant isolates. Notably, in companion animals, with a closest interaction with human, sul4 gene was detected. To our knowledge, this is the first report of the presence of sul4 gene in E. coli collected from animals, whereas previously the presence of this gene was reported in environmental, municipal wastewater and human clinical isolates. These results highlighted the importance of continuous antimicrobial resistant genes monitoring in animal species, with a special care to companion animals.

Asunto(s)

Antibacterianos , Farmacorresistencia Bacteriana , Escherichia coli , Mascotas , Aves de Corral , Sulfonamidas , Animales , Perros , Gatos , Sulfonamidas/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Porcinos , Bovinos , Antibacterianos/farmacología , Mascotas/microbiología , Farmacorresistencia Bacteriana/genética , Aves de Corral/microbiología , Pruebas de Sensibilidad Microbiana , Proteínas de Escherichia coli/genética , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Humanos , Ganado/microbiología

RESUMEN

BACKGROUND: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes. OBJECTIVE: The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity. METHOD: A maximum common substructure (MCS) and molecular docking were used to carry out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2. RESULTS: Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 µM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi. CONCLUSION: Compounds C7, C9, and C21 showed trypanocide activity; therefore, these results encourage the development of new trypanocidal agents based on their scaffold.

RESUMEN

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound healing. Resveratrol (RSV) is known for its antioxidant properties, but its limited bioavailability hinders its clinical use. This study investigated the potential of two RSV derivatives (1d and 1h) to address these limitations. The antioxidant abilities of 1d and 1h (5 µM) against DEX-induced oxidative stress (200 µM) were evaluated in human gingival fibroblasts (hGFs) and osteoblasts (hOBs). The effects of these compounds on cell viability, morphology, ROS levels, SOD activity, gene expression, and collagen production were evaluated. RSV derivatives, under DEX-induced oxidative stress condition, improved cell growth at 72 h (191.70 ± 10.92% for 1d+DEX and 184.80 ± 13.87% for 1h+DEX), morphology, and SOD activity (77.33 ± 3.35 OD for 1d+DEX; 76.87 ± 3.59 OD for 1h+DEX at 1 h), while reducing ROS levels (2417.33 ± 345.49 RFU for 1d+DEX and 1843.00 ± 98.53 RFU at 4 h), especially in hOBs. The co-treatment of RSV or derivatives with DEX restored the expression of genes that were downregulated by DEX, such as HO-1 (1.76 ± 0.05 for 1d+DEX and 1.79 ± 0.01 for 1h+DEX), CAT (0.97 ± 0.06 for 1d+DEX and 0.99 ± 0.03 for 1h+DEX), NRF2 (1.62 ± 0.04 for 1d+DEX and 1.91 ± 0.05 for 1h+DEX), SOD1 (1.63 ± 0.15 for 1d+DEX and 1.69 ± 0.04 for 1h+DEX). In addition, 1d and 1h preserved collagen production (111.79 ± 1.56 for 1d+DEX and 122.27 ± 1.56 for 1h+DEX). In conclusion, this study suggests that the RSV derivatives 1d and 1h hold promise as potential antioxidant agents to counteract DEX-induced oxidative stress. These findings contribute to the development of novel therapeutic strategies for managing oxidative stress-related oral conditions.

RESUMEN

This study describes the preparation of a cylindrical polymer foam column termed Chitosan/ß-Cyclodextrin/MIL-68(Al) (CS/ß-CD/MIL-68(Al)). An ice template-freeze drying technique was employed to prepare the CS/ß-CD/MIL-68(Al) foam column by embedding MIL-68(Al) in a polymer matrix comprising cross-linked chitosan (CS) and ß-cyclodextrin (ß-CD). The cylindrical CS/ß-CD/MIL-68(Al) foam was subsequently inserted into a syringe to develop a solid phase extraction (SPE) device. Without the requirement for an external force, the sample solution passed easily through the SPE column thanks to the porous structure of the CS/ß-CD/MIL-68(Al) foam column. Moreover, the CS/ß-CD/MIL-68(Al) foam column was thought to be a superior absorbent for SPE since it included the adsorptive benefits of CS, ß-CD, and MIL-68(Al). The SPE was utilized in conjunction with high-performance liquid chromatography to analyze six sulfonamides found in milk, urine, and water. With matrix effects ranging from 80.49 % to 104.9 % with RSD values of 0.4-14.0 %, the method showed high recoveries ranging from 80.6 to 107.4 % for water samples, 93.4-105.2 % for urine, and 87.4-100.9 % for milk. It also demonstrated good linearity in the range of 10-258 ng·mL-1 with the limits of detection ranging from 1.88 to 2.58 ng·mL-1. The cylindrical CS/ß-CD/MIL-68(Al) foam column prepared in this work offered several advantages, including its simple fabrication, excellent water stability, absence of pollutants, biodegradability, and reusability. It is particularly well-suited for SPE. Furthermore, the developed SPE method, employing CS/ß-CD/MIL-68(Al) foam column, is straightforward and precise, and its benefits, including affordability, ease of preparation, lack of specialized equipment, and solvent economy, underline its broad applicability for the pretreatment of aqueous samples.

Asunto(s)

Quitosano , Límite de Detección , Estructuras Metalorgánicas , Leche , Extracción en Fase Sólida , Sulfonamidas , beta-Ciclodextrinas , Extracción en Fase Sólida/métodos , Quitosano/química , beta-Ciclodextrinas/química , Leche/química , Estructuras Metalorgánicas/química , Sulfonamidas/orina , Sulfonamidas/aislamiento & purificación , Sulfonamidas/química , Animales , Cromatografía Líquida de Alta Presión/métodos , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Humanos , Reproducibilidad de los Resultados

RESUMEN

A sustainable and scalable protocol for synthesizing variously functionalized sulfonamides, from amines and sulfonyl chlorides, has been developed using environmentally responsible and reusable choline chloride (ChCl)-based deep eutectic solvents (DESs). In ChCl/glycerol (1:2 mol mol-1) and ChCl/urea (1:2 mol mol-1), these reactions yield up to 97% under aerobic conditions at ambient temperature within 2-12 h. The practicality of the method is exemplified by the sustainable synthesis of an FFA4 agonist and a key building block en route to anti-Alzheimer drug BMS-299897. A subtle interplay of electronic effects and the solubility characteristics of the starting materials in the aforementioned DESs seem to be responsible for driving the reaction successfully over the hydrolysis of sulfonyl chlorides. The procedure's eco-friendliness is validated  by quantitative metrics like the E-factor and the EcoScale, with products isolated by extraction or filtration after decantation.

RESUMEN

Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use. Here we present a new family of N-indolyl-3,4,5-trimethoxybenzenesulfonamide derivatives with modifications on the indole system at positions 1 and 3 and on the sulfonamide nitrogen. We synthesized and screened against HeLa cells 34 novel indolic benzenesulfonamides. The most potent derivatives (1.7-109 nM) were tested against a broad panel of cancer cell lines, which revealed that substituted benzenesulfonamides analogs had highest potency. Importantly, these compounds were only moderately toxic to non-tumorigenic cells, suggesting the presence of a therapeutic index. Consistent with known clinical anti-tubulin agents, these compounds arrested the cell cycle at G2/M phase. Mechanistically, they induced apoptosis via caspase 3/7 activation, which occurred during M arrest. The substituents on the sulfonamide nitrogen appeared to determine different mechanistic results and cell fates. These results suggest that the compounds act differently depending on the bridge substituents, thus making them very interesting as mechanistic probes as well as potential drugs for further development.

Asunto(s)

Antineoplásicos , Apoptosis , Bencenosulfonamidas , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Indoles , Sulfonamidas , Humanos , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Apoptosis/efectos de los fármacos , Estructura Molecular , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Relación Dosis-Respuesta a Droga , Nitrógeno/química , Línea Celular Tumoral , Células HeLa , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/química , Moduladores de Tubulina/síntesis química

RESUMEN

Introduction: New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species. Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides (3a-c) by reacting 5-bromothiophene-2-sulfonamide (1) with various alkyl bromides (2) using LiH. We also synthesized a series of compounds (4a-g) from compound (3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56-72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I. Results: The compound (3b) with favourable drug candidate status, MIC of 0.39 µg/mL, and MBC of 0.78 µg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions. Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option.

RESUMEN

A family of new compounds with sulfonamide and amide functional groups as potential Alzheimer's disease drugs were prepared by multistep synthesis. Thermal stability measurements recorded the initial decomposition in the range of 200-220°C, close above the melting point. The final compounds were tested for their ability to inhibit acetylcholinesterase and butyrylcholinesterase, and the in vitro dissolution behavior of selected compounds was studied through both lipophilic and hydrophilic matrix tablets. All nine tested derivatives were even more active in inhibiting acetylcholinesterase than the clinically used rivastigmine. Regression analysis of the obtained dissolution profiles was performed, and the effects of the pH and the release mechanism were determined. Some substances showed remarkable biological activity and became a subject of interest for further extensive study.