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Environment International May 2024DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular...
DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular metabolic responses towards pollutants. However, the mechanism underlying site-specific aberrant DNA methylation and metabolic disorders under pollutant stresses remained elusive. Herein, the multilevel omics interferences of sulfonamides (i.e., sulfadiazine and sulfamerazine), a group of antibiotics pervasive in farmland soils, towards rice in 14 days of 1 mg/L hydroponic exposure were systematically evaluated. Metabolome and transcriptome analyses showed that 57.1-71.4 % of mono- and disaccharides were accumulated, and the differentially expressed genes were involved in the promotion of sugar hydrolysis, as well as the detoxification of sulfonamides. Most differentially methylated regions (DMRs) were hypomethylated ones (accounting for 87-95 %), and 92 % of which were located in the CHH context (H = A, C, or T base). KEGG enrichment analysis revealed that CHH-DMRs in the promoter regions were enriched in sugar metabolism. To reveal the significant hypomethylation of CHH, multi-spectroscopic and thermodynamic approaches, combined with molecular simulation were conducted to investigate the molecular interaction between sulfonamides and DNA in different sequence contexts, and the result demonstrated that sulfonamides would insert into the minor grooves of DNA, and exhibited a stronger affinity with the CHH contexts of DNA compared to CG or CHG contexts. Computational modeling of DNA 3D structures further confirmed that the binding led to a pitch increase of 0.1 Å and a 3.8° decrease in the twist angle of DNA in the CHH context. This specific interaction and the downregulation of methyltransferase CMT2 (logFC = -4.04) inhibited the DNA methylation. These results indicated that DNA methylation-based assessment was useful for metabolic toxicity prediction and health risk assessment.
Topics: DNA Methylation; Oryza; Sulfonamides; Carbohydrate Metabolism; Soil Pollutants
PubMed: 38735075
DOI: 10.1016/j.envint.2024.108737 -
Biomolecules Apr 2024This scientific study employs the Taylor dispersion technique for diffusion measurements to investigate the interaction between sulfamerazine (NaSMR) and macromolecular...
This scientific study employs the Taylor dispersion technique for diffusion measurements to investigate the interaction between sulfamerazine (NaSMR) and macromolecular cyclodextrins (-CD and HP--CD). The results reveal that the presence of -CD influences the diffusion of the solution component, NaSMR, indicating a counterflow of this drug due to solute interaction. However, diffusion data indicate no inclusion of NaSMR within the sterically hindered HP--CD cavity. Additionally, toxicity tests were conducted, including pollen germination () and growth curve assays in BY-2 cells. The pollen germination tests demonstrate a reduction in sulfamerazine toxicity, suggesting potential applications for this antimicrobial agent with diminished adverse effects. This comprehensive investigation contributes to a deeper understanding of sulfamerazine-cyclodextrin interactions and their implications for pharmaceutical and biological systems.
Topics: Sulfamerazine; Diffusion; Cyclodextrins; Toxicity Tests; beta-Cyclodextrins; 2-Hydroxypropyl-beta-cyclodextrin
PubMed: 38672478
DOI: 10.3390/biom14040462 -
Journal of Veterinary Research Mar 2024The article presents a rapid and simple analytical procedure for determination of four sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine and sulfamethoxazole),...
INTRODUCTION
The article presents a rapid and simple analytical procedure for determination of four sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine and sulfamethoxazole), trimethoprim, tylosin and amoxicillin in animal medicated feed.
MATERIAL AND METHODS
Eighteen medicated feed samples were analysed for active substances. The analytical protocol used a mixture of acetonitrile and 0.05 M phosphoric buffer, pH 4.5 for the extraction of seven antibacterial substances. After extraction, the samples were diluted in Milli-Q water and analysed by liquid chromatography with mass spectrometry. The developed procedure was subjected to validation in terms of linearity, selectivity, limits of quantification and determination, repeatability, reproducibility and uncertainty.
RESULTS
The validation of the method was carried out in accordance with the criteria set out in Commission Implementing Regulation (EU) 2021/808 and ICH guidelines. This method provided average recoveries of 90.8 to 104.5% with coefficients of variation for repeatability and reproducibility in the ranges of 3.2-6.9% and 5.2-8.3%, respectively for all analysed antibacterial substances. The limit of detection and limit of quantification for all seven analytes ranged from 5.4 mg/kg to 48.3 mg/kg and from 10.4 mg/kg to 119.3 mg/kg, respectively. The uncertainty of the method depending on the compound varied from 14.0% to 24.0%. The validated method was successfully applied to the 18 medicated feeds.
CONCLUSION
The developed method can be successfully used to routinely control the content and homogeneity of seven antibacterial substances in medicated feed.
PubMed: 38525232
DOI: 10.2478/jvetres-2024-0011 -
Inorganic Chemistry Jan 2024Nanoceria is a promising nanomaterial for the catalytic hydrolysis of a wide variety of substances. In this study, it was experimentally demonstrated for the first time...
Nanoceria is a promising nanomaterial for the catalytic hydrolysis of a wide variety of substances. In this study, it was experimentally demonstrated for the first time that CeO nanostructures show extraordinary reactivity toward sulfonamide drugs (sulfadimethoxine, sulfamerazine, and sulfapyridine) in aqueous solution without any illumination, activation, or pH adjustment. Hydrolytic cleavage of various bonds, including S-N, C-N, and C-S, was proposed as the main reaction mechanism and was indicated by the formation of various reaction products, namely, sulfanilic acid, sulfanilamide, and aniline, which were identified by HPLC-DAD, LC-MS/MS, and NMR spectroscopy. The kinetics and efficiency of the ceria-catalyzed hydrolytic cleavage were dependent on the structure of the sulfonamide molecule and physicochemical properties of Nanoceria prepared by three different precipitation methods. However, in general, all three ceria samples were able to cleave SA drugs tested, proving the robust and unique surface reactivity toward these compounds inherent to cerium dioxide. The demonstrated reactivity of CeO to molecules containing sulfonamide or even sulfonyl (and similar) functional groups may be significant for both heterogeneous catalysis and environmentally important degradation reactions.
PubMed: 38234266
DOI: 10.1021/acs.inorgchem.3c04367 -
ACS Omega Dec 2023The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a...
Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure-Activity Relationship, Kinetics Mechanism, and In Silico Studies.
The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a dynamic field of study and advancement within medicinal chemistry. This research demonstrates the conjugation of diclofenac and mefenamic acid with sulfa drugs and their screening for urease inhibition. These conjugates' structural confirmation was performed using elemental analysis and spectroscopic methods, including IR, H NMR, and C NMR. Diclofenac conjugated with sulfanilamide (4), sulfacetamide (10), and mefenamic acid conjugated with sulfanilamide (12), and sulfamethoxazole (17) was found potent and demonstrated urease inhibition competitively, with IC (μM) values 3.59 ± 0.07, 5.49 ± 0.34, 7.92 ± 0.27, and 8.35 ± 0.26, respectively. Diclofenac conjugated with sulfathiazole (6), sulfamerazine (8), and sulfaguanidine (11), while mefenamic acid conjugated with sulfisoxazole (13), sulfathiazole (14), and sulfadiazine (15) exhibited a mixed mode of urease inhibition. The IC (μM) values were 16.19 ± 0.21, 9.50 ± 0.28, 4.35 ± 0.23, 15.86 ± 0.25, 14.80 ± 0.27, and 7.92 ± 0.27, respectively. Furthermore, molecular docking studies were employed to predict the binding pose of competitive inhibitors at the urease active site. These conjugates generated stable complexes with the urease protein observed through molecular dynamics (MD) simulations, where no conformational changes occurred throughout the simulations. These results highlight the potential for approved therapeutic molecule conjugates to give rise to new categories of pharmacological agents for urease inhibition. The structural similarity of sulfonamides with urea allows them to compete with urea for binding to the active site of the urease enzyme. Sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) can interact hydrophobically with the active site of the urease enzyme, which may disturb its structure and catalytic activity. Therefore, these conjugates may be helpful in the development of novel pharmacological agents for the treatment of a variety of illnesses in which the urease enzyme is involved.
PubMed: 38075833
DOI: 10.1021/acsomega.3c07275 -
Environmental Science and Pollution... Nov 2023Sulfonamides circulating in the environment lead to disturbances in food chains and local ecosystems, but most importantly contribute to development of resistance genes,...
Sulfonamides circulating in the environment lead to disturbances in food chains and local ecosystems, but most importantly contribute to development of resistance genes, which generate problems with multidrug-resistant bacterial infections treatment. In urban areas, sources of sulfonamide distribution in soils have received comparatively less attention in contrast to rural regions, where animal-derived manure, used as a natural fertilizer, is considered the main source. The aim of this study was to determine eight sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine, sulfamethizole, sulfamethoxazole, sulfapyridine, sulfathiazole, and sulfisoxazole) in environmental soil samples collected from urbanized regions in Silesian Voivodeship with increased animal activity. These soils were grouped according to the organic carbon content. It was necessary to develop versatile and efficient extraction and determination method to analyze selected sulfonamides in various soil types. The developed LC-MS/MS method for sulfonamides analyzing was validated. The obtained recoveries exceeded 45% for soil with medium organic carbon content and 88% for sample with a very low organic carbon content (arenaceous quartz). The obtained results show the high impact of organic matter on analytes adsorption in soil, which influences recovery. All eight sulfa drugs were determined in environmental samples in the concentration range 1.5-10.5 ng g. The transformation products of the analytes were also identified, and 29 transformation products were detected in 24 out of 27 extracts from soil samples.
Topics: Animals; Sulfonamides; Soil; Chromatography, Liquid; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Poland; Ecosystem; Sulfanilamide; Carbon; Anti-Bacterial Agents
PubMed: 37843710
DOI: 10.1007/s11356-023-30146-y -
Molecules (Basel, Switzerland) Aug 2023The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The...
The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative was formed when compound was treated with sulfamerazine. Also, compound was reacted with NH-NH in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and/or diethyl oxalate to produce quinazoline derivatives , , and , respectively. The results of the pharmacological study indicated that the synthesized - and derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC values of the target compounds -, and against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 µM, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 µM, respectively. The IC values of the target compounds -, and against sPLA2 were 2.84, 2.73, 1.016, and 4.45 µM, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 µM, respectively. The IC values of the target compounds -, and against cPLA2 were 1.44, 2.08, 0.5, and 2.39 µM, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 µM, respectively. Also, incubation of lung cells with LPS plus derivatives -, and caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-α, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds - and and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds - and with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 µM, indicating that it has low effectiveness.
Topics: Humans; Molecular Docking Simulation; COVID-19; Ivermectin; SARS-CoV-2; Sulfamerazine; Structure-Activity Relationship; Phospholipases A2, Cytosolic
PubMed: 37630304
DOI: 10.3390/molecules28166052 -
Molecules (Basel, Switzerland) Jul 2023The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a...
New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies.
The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide-sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.
Topics: Molecular Docking Simulation; Flurbiprofen; Ibuprofen; Enzyme Inhibitors; Sulfacetamide; Kinetics; Urease; Sulfamerazine; Canavalia; Structure-Activity Relationship; Sulfanilamide; Sulfonamides; Molecular Structure
PubMed: 37513261
DOI: 10.3390/molecules28145389 -
Molecules (Basel, Switzerland) Apr 2023A novel, molecularly imprinted, upconversion fluorescence probe (UCNP@MIFP) for sulfonamide sensing was fabricated by Pickering emulsion polymerization using UCNP@SiO...
A Novel Sulfonamide, Molecularly Imprinted, Upconversion Fluorescence Probe Prepared by Pickering Emulsion Polymerization and Its Adsorption and Optical Sensing Performance.
A novel, molecularly imprinted, upconversion fluorescence probe (UCNP@MIFP) for sulfonamide sensing was fabricated by Pickering emulsion polymerization using UCNP@SiO particles as the stabilizer and sulfamethazine/sulfamerazine as the co-templates. The synthesis conditions of the UCNP@MIFP were optimized, and the synthesized probe was characterized by scanning electron microscopy, Fourier transform infrared spectrometer, thermogravimetric analyzer, and fluorescence spectrometer. The UCNP@MIFPs showed a good adsorption capacity and a fast kinetic feature for the template. The selectivity experiment revealed that the UCNP@MIFP has a broad-spectrum molecular recognition capability. Good linear relationships were obtained over the concentration range of 1-10 ng/mL for sulfamerazine, sulfamethazine, sulfathiazole, and sulfafurazole, with low limits of detection in the range of 1.37-2.35 ng/mL. The prepared UCNP@MIFP has the potential to detect four sulfonamide residues in food and environmental water.
PubMed: 37110624
DOI: 10.3390/molecules28083391 -
Molecules (Basel, Switzerland) Feb 2023Developing a simple and efficient method for removing organic micropollutants from aqueous systems is crucial. The present study describes the preparation and...
Developing a simple and efficient method for removing organic micropollutants from aqueous systems is crucial. The present study describes the preparation and application, for the first time, of novel MXene-decorated bismuth ferrite nanocomposites (BiFeO/MXene) for the removal of six sulfonamides including sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMZ), sulfamethazine (SMTZ), sulfamethoxazole (SMXZ) and sulfisoxazole (SXZ). The properties of BiFeO/MXene are enhanced by the presence of BiFeO nanoparticles, which provide a large surface area to facilitate the removal of sulfonamides. More importantly, BiFeO/MXene composites demonstrated remarkable sulfonamide adsorption capabilities compared to pristine MXene, which is due to the synergistic effect between BiFeO and MXene. The kinetics and isotherm models of sulfonamide adsorption on BiFeO/MXene are consistent with a pseudo-second-order kinetics and Langmuir model. BiFeO/MXene had appreciable reusability after five adsorption-desorption cycles. Furthermore, BiFeO/MXene is stable and retains its original properties upon desorption. The present work provides an effective method for eliminating sulfonamides from water by exploiting the excellent texture properties of BiFeO/MXene.
Topics: Sulfonamides; Bismuth; Sulfanilamide; Water; Nanocomposites; Adsorption; Water Pollutants, Chemical; Kinetics
PubMed: 36838529
DOI: 10.3390/molecules28041541