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Angewandte Chemie (International Ed. in... Oct 2019Sulfonimidamides are intriguing new motifs for medicinal and agrochemistry, and provide attractive bioisosteres for sulfonamides. However, there remain few operationally... (Review)
Review
Sulfonimidamides are intriguing new motifs for medicinal and agrochemistry, and provide attractive bioisosteres for sulfonamides. However, there remain few operationally simple methods for their preparation. Here, the synthesis of NH-sulfonimidamides is achieved directly from sulfenamides, themselves readily formed in one step from amines and disulfides. A highly chemoselective and one-pot NH and O transfer is developed, mediated by PhIO in iPrOH, using ammonium carbamate as the NH source, and in the presence of 1 equivalent of acetic acid. A wide range of functional groups are tolerated under the developed reaction conditions, which also enables the functionalization of the antidepressants desipramine and fluoxetine and the preparation of an aza analogue of the drug probenecid. The reaction is shown to proceed via different and concurrent mechanistic pathways, including the formation of novel S≡N sulfanenitrile species as intermediates. Several alkoxy-amino-λ -sulfanenitriles are prepared with different alcohols, and shown to be alkylating agents to a range of nucleophiles.
Topics: Alcohols; Amines; Molecular Structure; Nitriles; Sulfamerazine; Sulfonamides
PubMed: 31390133
DOI: 10.1002/anie.201906001 -
Archiv Der Pharmazie Jan 2021A novel series of sulfonamides, 4-(3-phenyltriaz-1-en-1-yl)-N-(4-methyl-2-pyrimidinyl)benzenesulfonamides (1-9), was designed and synthesized by the diazo reaction...
A novel series of sulfonamides, 4-(3-phenyltriaz-1-en-1-yl)-N-(4-methyl-2-pyrimidinyl)benzenesulfonamides (1-9), was designed and synthesized by the diazo reaction between sulfamerazine and substituted aromatic amines for the first time. Their chemical structures were characterized by H nuclear magnetic resonance (NMR), C NMR, and high-resolution mass spectra. The newly synthesized compounds were evaluated in terms of acetylcholineasterase (AChE) and human carbonic anhydrases (hCA) I and II isoenzymes inhibitory activities. According to the AChE inhibition results, the K values of the compounds 1-9 were in the range of 19.9 ± 1.5 to 96.5 ± 20.7 nM against AChE. Tacrine was used as the reference drug and its K value was 49.2 ± 2.7 nM against AChE. The K values of the compounds 1-9 were in the range of 10.2 ± 2.6 to 101.4 ± 27.8 nM against hCA I, whereas they were 18.3 ± 4.4 to 48.1 ± 4.5 nM against hCA II. Acetazolamide was used as a reference drug and its K values were 72.2 ± 5.4 and 52.2 ± 5.7 nM against hCA I and hCA II, respectively. The most active compounds, 1 (nonsubstituted) against AChE, 5 (4-ethoxy-substituted) against hCA I, and 8 (4-bromo-substituted) against hCA II, were chosen and docked at the binding sites of these enzymes to explain the inhibitory activities of the series. The newly synthesized compounds presented satisfactory pharmacokinetic properties via the estimation of ADME properties.
Topics: Acetylcholinesterase; Carbonic Anhydrase I; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Cholinesterase Inhibitors; Computer Simulation; Humans; Structure-Activity Relationship; Sulfamerazine; Triazenes
PubMed: 32984993
DOI: 10.1002/ardp.202000243 -
Environment International Jul 2018Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from... (Meta-Analysis)
Meta-Analysis Review
Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Genes, Bacterial; Geologic Sediments; Lakes
PubMed: 29653401
DOI: 10.1016/j.envint.2018.04.011 -
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 -
Bioresource Technology Sep 2018Pollution of water by single antibiotics has been investigated in depth. However, in reality, a wide range of different contaminants is often mixed in the aquatic...
Pollution of water by single antibiotics has been investigated in depth. However, in reality, a wide range of different contaminants is often mixed in the aquatic environment (contaminant cocktail). Here, single and competitive sorption dynamics of ionizable norfloxacin (NOR), sulfamerazine (SMR) and oxytetracycline (OTC) by both pristine and modified biochars were investigated. Sorption kinetics of the three antibiotics was faster in ternary-solute than single-solute system. Sorption efficiency was enhanced in the competitive system for NOR by the pristine biochar, and for OTC by both the pristine biochar and the modified biochar, while SMR sorption by the pristine biochar and the KOH-modified biochar was inhibited. Sorption was governed by electrostatic interactions, π-π EDA and H-bonds for antibiotics sorption by biochar. SMR and OTC sorption by biochar was influenced by cation bridging and surface complexation, respectively. This research finding will guide the development of treatment procedures for water polluted by multiple antibiotics.
Topics: Adsorption; Charcoal; Norfloxacin; Oxytetracycline; Sulfamerazine; Water Purification
PubMed: 29763802
DOI: 10.1016/j.biortech.2018.05.022 -
Journal of Environmental Management Jan 2019Understanding the dynamics of veterinary antibiotic and related antibiotic resistance genes (ARGs) during swine manure composting is crucial in assessing the...
Understanding the dynamics of veterinary antibiotic and related antibiotic resistance genes (ARGs) during swine manure composting is crucial in assessing the environmental risk of antibiotics, which could effectively reduce their impact in natural environments. This study investigated the dissipation of oxytetracycline (OTC), sulfamerazine (SM1) and ciprofloxacin (CIP) as well as the behaviour of their corresponding ARGs during swine manure composting. These antibiotics were added at two concentration levels and two different methods of addition (single/mixture). The results indicated that the removal efficiency of antibiotics by composting were ≥85%, except for the single-SM1 treatment. The tetracycline resistance genes (TRGs) encoding ribosomal protection proteins (RPP) and efflux pump (EFP) and fluoroquinolone resistance genes (FRGs) could be effectively removed after 42 days. On the contrary, the TRGs encoding enzymatic inactivation (EI) and sulfonamide resistance genes (SRGs) were enriched up to 31-fold (sul 2 in single-low-SM1). Statistical analyses indicated that the behaviour of these class antibiotics and ARGs were controlled by microbial activity and significantly influenced by environmental factors (mainly C/N, moisture and pH) throughout the composting process.
Topics: Animals; Anti-Bacterial Agents; Ciprofloxacin; Composting; Drug Resistance, Microbial; Manure; Oxytetracycline; Sulfamerazine; Swine
PubMed: 30278273
DOI: 10.1016/j.jenvman.2018.09.074 -
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 -
Frontiers in Microbiology 2018Halophytes are associated with the intertidal forest ecosystem of Saudi Arabia and seemingly have an immense potential for yielding useful and important natural...
Halophytes are associated with the intertidal forest ecosystem of Saudi Arabia and seemingly have an immense potential for yielding useful and important natural products. In this study we have aimed to isolate and characterize the endophytic and rhizospheric bacterial communities from the halophyte, , In addition these bacterial strains were identified and selected strains were further studied for bioactive secondary metabolites. At least 168 rhizspheric and endophytic bacteria were isolated and of these 22 were active antagonists against the oomycetous fungal plant pathogens, and . Active cultures were mainly identified with molecular techniques (16S r DNA) and this revealed 95.7-100% sequence similarities with relevant type strains. These microorgansims were grouped into four major classes: , β, and γ. Production of fungal cell wall lytic enzymes was detected mostly in members of and . PCR screening for type I polyketide synthases (PKS-I), type II polyketide synthases (PKS-II) and nonribosomal peptide synthetases (NRPS) revealed 13 of the 22 strains (59%) were positive for at least one of these important biosynthetic genes that are known to be involved in the synthesis of important antibiotics. Four bacterial strains of with potential antagonistic activity including two rhizobacteria, EA52 ( sp.), EA58 ( sp.) and endophytic bacteria . (EA65) and sp. (EA67) were selected for secondary metabolite analyses using LC-MS. As a result, the presence of different bioactive compounds in the culture extracts was detected some of which are already reported for their diverse biological activities including antibiotics such as Sulfamethoxypyridazine, Sulfamerazine, and Dimetridazole. In conclusion, this study provides an insight into antagonistic bacterial population especially the from , producing antifungal metabolites of medical significance and characterized taxonomically in future.
PubMed: 29445362
DOI: 10.3389/fmicb.2018.00065 -
Molecules (Basel, Switzerland) Mar 2022Antibacterial substances such as sulfonamides are widely used in veterinary medicine to treat many bacterial diseases. After their administration to animals, up to 90%...
Antibacterial substances such as sulfonamides are widely used in veterinary medicine to treat many bacterial diseases. After their administration to animals, up to 90% of the initial dose of the antibiotic is excreted in the feces and/or urine, which can be applied to farmland as natural or organic fertilizers. In this work, an analytical method was developed with the use of HPLC-FLD for the detection and quantification of five sulfonamides (sulfaguanidine, sulfadiazine, sulfamerazine, sulamethazine and sulfamethoxazol) in poultry and pig feces, slurry and digestates. The method was validated according to EU requirements (Commission Decision 2002/657/EC and VICH GL49). Linearity, decision limit, detection capability, detection and quantification limits, recovery, precision, and selectivity were determined, and adequate results were obtained. Using the HPLC-FLD method for all analyzed matrices, recoveries were satisfactory (77.00-121.16%), with repeatability and reproducibility in the range of 4.36-17.34% to 7.94-18.55%, respectively. Decision limit (CCα) and detection capability (CCβ) were 33.87-67.63 and 53.36-92.00 µg/kg, respectively, and limit of detection (LOD) and limit of quantification (LOQ) were 13.53-23.30 and 26.02-40.38 µg/kg, respectively, depending on the analyte. The forty-four samples of natural and organic fertilizers were analyzed, and four samples showed sulfamethoxazole in the amount from range 158 to 11,070 µg/kg. The application of antibiotics including sulfonamides for farming animals is widespread and may lead to the development of antibiotic resistance and other environmental effects.
Topics: Animals; Chromatography, High Pressure Liquid; Fertilizers; Poland; Reproducibility of Results; Sulfonamides; Swine
PubMed: 35335395
DOI: 10.3390/molecules27062031