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Journal of Pharmaceutical and... Sep 2023This study aimed to develop a molecularly imprinted polymer (MIP) sensor using electropolymerization of thiophene acetic acid monomer around template molecules,...
ZnO and Au nanoparticles supported highly sensitive and selective electrochemical sensor based on molecularly imprinted polymer for sulfaguanidine and sulfamerazine detection.
This study aimed to develop a molecularly imprinted polymer (MIP) sensor using electropolymerization of thiophene acetic acid monomer around template molecules, sulfaguanidine (SGN) and sulfamerazine (SMR), for selective and sensitive detection of both antibiotics. Au nanoparticles were then deposited on the modified electrode surface, and SGN and SMR were extracted from the resulting layer. Surface characterization, changes in the oxidation peak current of both analytes, and investigation of the electrochemical properties of the MIP sensor were examined using scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry. The developed MIP sensor with Au nanoparticles showed a detection limit of 0.030 µmol L and 0.046 µmol L for SGN and SMR, respectively, with excellent selectivity in the presence of interferents. The sensor was successfully used for SGN and SMR analysis in human fluids, including blood serum and urine, with excellent stability and reproducibility.
Topics: Humans; Molecularly Imprinted Polymers; Sulfamerazine; Sulfaguanidine; Gold; Zinc Oxide; Metal Nanoparticles; Reproducibility of Results; Molecular Imprinting; Electrochemical Techniques; Electrodes; Limit of Detection
PubMed: 37336038
DOI: 10.1016/j.jpba.2023.115518 -
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 -
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 -
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 -
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 -
Environmental Pollution (Barking, Essex... Nov 2023Sulfadiazine and its derivatives (sulfonamides, SAs) could induce distinct biotoxic, metabolic and physiological abnormalities, potentially due to their subtle...
Sulfadiazine and its derivatives (sulfonamides, SAs) could induce distinct biotoxic, metabolic and physiological abnormalities, potentially due to their subtle structural differences. This study conducted an in-depth investigation on the interactions between SA homologues, i.e. sulfadiazine (SD), sulfamerazine (SD1), and sulfamethazine (SD2), and the key metabolic enzyme (glycosyltransferase, GT) in rice (Oryza sativa L.). Untargeted screening of SA metabolites revealed that GT-catalyzed glycosylation was the primary transformation pathway of SAs in rice. Molecular docking identified that the binding sites of SAs on GT (D0TZD6) were responsible for transferring sugar moiety to synthesize polysaccharides and detoxify SAs. Specifically, amino acids in the GT-binding cavity (e.g., GLY487 and CYS486) formed stable hydrogen bonds with SAs (e.g., the sulfonamide group of SD). Molecular dynamics simulations revealed that SAs induced conformational changes in GT ligand binding domain, which was supported by the significantly decreased GT activity and gene expression level. As evidenced by proteomics and metabolomics, SAs inhibited the transfer and synthesis of sugar but stimulated sugar decomposition in rice leaves, leading to the accumulation of mono- and disaccharides in rice leaves. While the differences in the increased sugar content by SD (24.3%, compared with control), SD1 (11.1%), and SD2 (6.24%) can be attributed to their number of methyl groups (0, 1, 2, respectively), which determined the steric hindrance and hydrogen bonds formation with GT. This study suggested that the disturbances on crop sugar metabolism by homologues contaminants are determined by the interaction between the contaminants and the target enzyme, and are greatly dependent on the steric hindrance effects contributed by their side chains. The results are of importance to identify priority pollutants and ensure crop quality in contaminated fields.
Topics: Oryza; Glycosyltransferases; Molecular Docking Simulation; Sulfanilamide; Sulfadiazine; Sulfonamides; Metabolic Diseases; Sugars
PubMed: 37669699
DOI: 10.1016/j.envpol.2023.122486 -
The Science of the Total Environment Aug 2023Sulfamerazine (SM) is a commonly used antibiotic and have been widely used to control various bacterial infectious diseases. The structural composition of colored...
Sulfamerazine (SM) is a commonly used antibiotic and have been widely used to control various bacterial infectious diseases. The structural composition of colored dissolved organic matter (CDOM) is known to be a major factor that influences the indirect photodegradation of SM, yet the influence mechanism remains unknown. In order to understand this mechanism, CDOM from different sources was fractionated using ultrafiltration and XAD resin, and characterized using UV-vis absorption and fluorescence spectroscopy. The indirect photodegradation of SM in these CDOM fractions was then investigated. Humic acid (JKHA) and Suwannee River natural organic matter (SRNOM) were used in this study. The results showed that CDOM could be divided into four components (three humic-like components and one protein-like component), and terrestrial humic-like components C1 and C2 were found to be the main components that promote SM indirect photodegradation due to their high aromaticity. The indirect photodegradation of SM was much faster in low molecular weight (MW) solutions, whose structures were dominated by greater aromaticity and terrestrial fluorophores in JKHA and higher terrestrial fluorophores in SRNOM. The HIA and HIB fractions of SRNOM contained large aromaticity and high fluorescence intensities of C1 and C2, resulting in a greater indirect photodegradation rate of SM. The HOA and HIB fractions of JKHA had abundant terrestrial humic-like components and contributed more to SM indirect photodegradation.
Topics: Sulfamerazine; Dissolved Organic Matter; Organic Chemicals; Photolysis; Anti-Bacterial Agents; Rivers; Spectrometry, Fluorescence; China
PubMed: 37201832
DOI: 10.1016/j.scitotenv.2023.164231 -
The Journal of Organic Chemistry Jul 2023A novel and efficient -arylation of sulfenamides with diaryliodonium salts for the synthesis of sulfilimines is developed. The reaction proceeds smoothly under...
A novel and efficient -arylation of sulfenamides with diaryliodonium salts for the synthesis of sulfilimines is developed. The reaction proceeds smoothly under transition-metal-free and air conditions, giving rapid access to sulfilimines in good to excellent yields via selective S-C bond formation. This protocol is scalable and exhibits a broad substrate scope, good functional group tolerance, and excellent chemoselectivity.
Topics: Metals; Sulfamerazine; Transition Elements
PubMed: 37327035
DOI: 10.1021/acs.joc.3c00961 -
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 -
The Science of the Total Environment Nov 2023As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and...
As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and non-biodegradable MPs in the aquatic environment, the adsorption behaviors of polyamide (PA) and polylactic acid (PLA) towards two sulfonamide antibiotics (SAs) were investigated. Both chemical and photo-aging were used to handle the virgin MPs. Compared with PA, PLA was aged more drastically, showing the obvious grooves, notches and folds. However, due to the higher temperature during chemical aging, the tiny KPLA (PLA aged by KSO) particles were agglomerated and the specific surface area was reduced to nearly 95 %. For PA, the oxidation of chemical aging was stronger than photo-aging. After aging, the hydrophilicity and polarity of MPs increased. In the adsorption experiments, the adsorption capacity of PA towards SAs was 1.7 times higher than that of PLA. Aging process enabled the adsorption capacity of PLA increased 1.22-3.18 times. Overall, the adsorption capacity of sulfamethoxazole (SMX) by both MPs was superior to sulfamerazine (SMR). These results would help to understand the carrier effects and potential ecological risks of MPs towards co-existing contaminants.
PubMed: 37607636
DOI: 10.1016/j.scitotenv.2023.166452