-
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 -
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 -
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 -
Food Chemistry Jun 2023A lanthanide terbium/europium metal-organic framework (TbEu-MOF) was prepared by one-step solvothermal method at room temperature. A series of characterizations...
A lanthanide terbium/europium metal-organic framework (TbEu-MOF) was prepared by one-step solvothermal method at room temperature. A series of characterizations including scanning electron microscopy, powder X-ray diffraction spectra, Fourier transform infrared spectra and X-ray photoelectron spectroscopy were carried out to clarify the physical characteristics of the synthesized material. The data clarified that the prepared TbEu-MOF possessed rod-like morphology with a width of 1-2 μm, and had good crystal structure, good stability, response speed and excitation-independent emission feature. The bunchy TbEu-MOF was then used to construct fluorescent sensors for rapid identification of malachite green and sulfamerazine. It was revealed that the detection mechanism was inner filter effect. The effects of different parameters such as excitation wavelength and incubation times were investigated on the fluorescence analysis performance. The data clarified that the optimal excitation wavelength and incubation time was 240 nm and 3 min, respectively. The detection platform exhibited the high sensitivity and selectivity toward malachite green in the linear range of 2-180 μM and determined limit of detection was 1.12 μM. Besides, the proposed sensor allowed sensitive detection of sulfamerazine in the linear range of 2-140 μM with a low detection limit of 0.1 μM. Meaningfully, a smartphone application was designed to assist the proposed sensor to realize visual, intelligent and rapid detection of malachite green and sulfamerazine. Furthermore, the practical application of the proposed sensor has been also verified by high performance liquid chromatography, showing good accuracy, sensitivity and satisfactory recoveries. The results suggested that the TbEu-MOF-based ratiometric fluorescent sensor had the potential to become a promising technique for rapid detection of malachite green or sulfamerazine with smartphone application. Therefore, the prepared TbEu-MOF is one kind of efficient and cost-effective potential materials for developing fluorescent sensor for rapid, sensitive and selective detection of sulfamerazine and malachite.
Topics: Lanthanoid Series Elements; Sulfamerazine; Fluorescent Dyes
PubMed: 36623454
DOI: 10.1016/j.foodchem.2023.135390 -
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 -
The Science of the Total Environment Oct 2020In this study, nano-silica (Nano-SiO), oxidized (O-CNTs) and graphitized multi-walled carbon nanotubes (G-CNTs) were applied as model adsorbents to study the adsorption,...
In this study, nano-silica (Nano-SiO), oxidized (O-CNTs) and graphitized multi-walled carbon nanotubes (G-CNTs) were applied as model adsorbents to study the adsorption, desorption and coadsorption behaviors of sulfamerazine (SMR), Pb(II) and benzoic acid (BA). The results showed that charge assisted H-bond (CAHB) formation played an important role in adsorption of SMR and BA on O-riched nanomaterials. The adsorption capacities of Pb(II) on CNTs were 21.46- 26.77 times higher than that on Nano-SiO, which was mainly attributed to surface complexation and cation-π interaction. The fraction of Pb adsorbed in the inside channel of CNTs should not be ignored. In coexisting systems, the absolute sorption inhibition of the SMR (ΔQ) was compared with the amount of competitor adsorbed. Competitive sorption was observed as indicated by adding Pb(II) decreased adsorption of SMR on Nano-SiO (ΔQ > 0), but hardly affected SMR adsorption on CNTs (ΔQ ≈ 0) which was attributed to cation-π interaction. In addition, CAHB formed between SMR and Nano-SiO (ΔpK ≈ 4.34) was weaker than that formed between SMR and O-CNTs (ΔpK ≈ 3.15), which also consequently resulted in stronger competition of Pb(II) to SMR on Nano-SiO than that on O-CNTs. Moreover, coexisting BA increased adsorption of SMR on Nano-SiO and G-CNTs (ΔQ < 0), but did not result in an apparent competition on SMR adsorption by O-CNTs (ΔQ ≈ 0). These results emphasize that the environmental behaviors of a certain pollutant should be assessed carefully by considering the presence of other pollutants.
PubMed: 32526408
DOI: 10.1016/j.scitotenv.2020.139685 -
Analytica Chimica Acta Aug 2022A novel strategy utilizing the quartz crystal microbalance (QCM) was developed for the in situ discrimination of polymorphic nucleation (form-I and form-II) and phase...
A novel strategy utilizing the quartz crystal microbalance (QCM) was developed for the in situ discrimination of polymorphic nucleation (form-I and form-II) and phase transformation of sulfamerazine (SMZ) in cooling crystallization. According to Ostwald's rule of stages, metastable form-I of SMZ is first nucleated and then shifted to stable form-II by solution-mediated phase transformation. Through surface modification with the self-assembled monolayer technique of a functional group, QCM distinctively detects the formation of the two polymorphs. The results indicated that -NH (among the several functional groups tested) selectively accommodated stable form-II on the QCM sensor's surface and completely prevented the adsorption of metastable form-I on the surface. Therefore, the-NH-terminated QCM detected the formation of form-I only using the solution viscosity variation on the surface. However, it monitored the nucleation and growth of form-II via the solid mass change on the surface during the phase transformation of form-I to form-II. This strategy suggests a new and precise solution for in situ discrimination of SMZ polymorphs and their phase transformation.
Topics: Crystallization; Quartz; Quartz Crystal Microbalance Techniques; Sulfamerazine
PubMed: 35934408
DOI: 10.1016/j.aca.2022.340137