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Bioorganic & Medicinal Chemistry Jan 2018A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB and CB receptors. The...
A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB and CB receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB receptors (K values of 44.6 nM for CB receptors and >40 μM for CB receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB receptors with K values of 75.5 and 73.2 nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB receptor in the [S]-GTPγS binding assays, and none showed adequate predictive blood-brain barrier permeation, exhibiting low estimated LD. However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist.
Topics: Dose-Response Relationship, Drug; Humans; Ligands; Molecular Docking Simulation; Molecular Structure; Pyridazines; Receptor, Cannabinoid, CB1; Structure-Activity Relationship; Sulfamerazine; Sulfonamides
PubMed: 29229226
DOI: 10.1016/j.bmc.2017.11.051 -
Scientific Reports Apr 2019Type 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the...
Type 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the present study was to evaluate the effects of metformin, and its sulfenamide and sulfonamide derivatives (compounds 1-8) on the selected markers of endothelial function and blood coagulation. The integrity of endothelial cells(ECs) was examined using the real-time cell electric impedance system. Tissue Factor(TF) production, the release of von Willebrand Factor (vWF) and tissue plasminogen activator(t-PA) from ECs were determined using immunoenzymatic assays, while the process of platelet thrombus formation using the Total Thrombus-Formation Analysis System. Sulfenamide with n-butyl alkyl chain(3) does not interfere with ECs integrity, and viability (nCI = 1.03 ± 0.03 vs. 1.06 ± 0.11 for control), but possesses anticoagulation properties manifested by prolonged platelet-dependent thrombus formation (Occlusion Time 370.3 ± 77.0 s vs. 286.7 ± 65.5 s for control) in semi-physiological conditions. Both p- and o-nitro-benzenesulfonamides (compounds7,8) exhibit anti-coagulant properties demonstrated by decreased vWF release and prolonged parameters of platelet thrombus formation and total blood thrombogenicity. In conclusion, chemical modification of metformin scaffold into sulfenamides or sulfonamides might be regarded as a good starting point for the design and synthesis of novel biguanide-based compounds with anticoagulant properties and valuable features regarding endothelial function.
Topics: Diabetes Mellitus, Type 2; Human Umbilical Vein Endothelial Cells; Humans; Metformin; Myocytes, Smooth Muscle; Sulfamerazine; Sulfonamides; Thromboplastin; von Willebrand Factor
PubMed: 31024058
DOI: 10.1038/s41598-019-43083-z -
Ecotoxicology and Environmental Safety Sep 2022Sulfonamide antibiotics (SAs) are widely used in medicine, animal husbandry and aquaculture, and excessive intake of SAs may pose potential toxicity to organisms. The...
Sulfonamide antibiotics (SAs) are widely used in medicine, animal husbandry and aquaculture, and excessive intake of SAs may pose potential toxicity to organisms. The toxicological mechanisms of two classical SAs, sulfamerazine (SMR) and sulfamethoxazole (SMT), were investigated by molecular docking, DFT and multi-spectroscopic techniques using HSA and BSA as model proteins. The quenching of HSA/BSA endogenous fluorescence by SMR was higher than that by SMT due to the stronger binding effect of the pyrimidine ring on HSA/BSA compared to the oxazole ring, and that result was consistent with that predicted by DFT calculations. Thermodynamic parameters show that the binding of SAs to HSA/BSA is an exothermic process that proceeds spontaneously (ΔG < 0). Marker competition experiments illustrate that the binding site of SMR/SMT on serum albumin is located in subdomain IIIA. The combination of SAs and HSA/BSA is mainly realized by hydrogen bond and hydrophobic interaction, and the concept is also supported by molecular modeling. The reduced α-helix content of HSA/BSA induced by SMR/SMT indicates a greater stretching of the protein α-helix structure of the SMR/SMT-HSA/BSA. The results could provide useful toxicological information on the hazards of SAs in response to growing concern that SAs may pose a toxic threat to organisms.
Topics: Animals; Anti-Bacterial Agents; Binding Sites; Circular Dichroism; Density Functional Theory; Molecular Docking Simulation; Protein Binding; Serum Albumin, Bovine; Spectrometry, Fluorescence; Sulfanilamide; Sulfonamides; Thermodynamics
PubMed: 35987082
DOI: 10.1016/j.ecoenv.2022.113979 -
Spectrochimica Acta. Part A, Molecular... Jan 2024Sulfa drugs are frequently used to treat infections, particularly in antibiotic resistant people. There are several techniques available to determine sulfa drugs,...
Sulfa drugs are frequently used to treat infections, particularly in antibiotic resistant people. There are several techniques available to determine sulfa drugs, however, they are laborious operation, reagent consumption, expensive, and need specialized types of equipment. Here, a new, very simple and inexpensive paper-based analytical device described for the determination of five sulfa drugs: sulfacetamide, sulfadiazine, sulfamerazine, sulfamethoxazole, and sulfathiazole in pharmaceutical preparations. The method is a one-step reaction, based on the colorimetric reaction between acid-hydrolyzed sulfa drugs and 4-dimethylaminobenzaldehyde. Using a smartphone, the RGB value of color intensity was used as an analytical signal. The paper-based device displayed linear ranges of 0.10-5.00 µg mL, linear correlations ranging from 0.9903 to 0.9972, limits of detection 0.0030 to 0.0082 µg mL, and RSD of ≤0.258 under optimal conditions. The suggested approach was applied for determining five sulfa drugs in pharmaceutical formulations. This approach is appropriate for pharmaceutical applications since it is inexpensive, simple to utilize, sensitive, and selective.
PubMed: 37683435
DOI: 10.1016/j.saa.2023.123336 -
International Journal of Environmental... Oct 2022In the present study, PbO electrodes, doped with different doses of Er (0%, 0.5%, 1%, 2%, and 4%), were fabricated and characterized. Surface morphology characterization...
In the present study, PbO electrodes, doped with different doses of Er (0%, 0.5%, 1%, 2%, and 4%), were fabricated and characterized. Surface morphology characterization by SEM-EDS and XRD showed that Er was successfully doped into the PbO catalyst layer and the particle size of Er-PbO was reduced significantly. Electrochemical oxidation of sulfamerazine (SMR) in the Er-PbO anode system obeyed te pseudo first-order kinetic model with the order of 2% Er-PbO > 4% Er-PbO > 1% Er-PbO > 0.5% Er-PbO > 0% PbO. For 2% Er-PbO, was 1.39 h, which was only 0.93 h for 0% PbO. Effects of different operational parameters on SMR degradation in 2% Er-PbO anode system were investigated, including the initial pH of the electrolyte and current density. Under the situation of an initial pH of 3, a current density of 30 mA·cm, a concentration of SMR 30 mg L, and 0.2 M NaSO used as supporting electrolyte, SMR was totally removed in 3 h, and COD mineralization efficiency was achieved 71.3% after 6 h electrolysis. Furthermore, the degradation pathway of SMR was proposed as combining the active sites identification by density functional calculation (DFT) and intermediates detection by LC-MS. Results showed that Er-PbO has great potential for antibiotic wastewater treatment in practical applications.
Topics: Sulfonamides; Sulfamerazine; Water Pollutants, Chemical; Oxides; Electrodes; Sulfanilamide; Oxidation-Reduction; Anti-Bacterial Agents; Titanium
PubMed: 36294088
DOI: 10.3390/ijerph192013503 -
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 -
Materials Science & Engineering. C,... Oct 2018This paper describes the application of poly (ethylene glycol dimethacrylate-N-methacryloyl-L-tryptophane methyl ester) [p(EGDMA-MATrp)] microspheres as an affinity...
This paper describes the application of poly (ethylene glycol dimethacrylate-N-methacryloyl-L-tryptophane methyl ester) [p(EGDMA-MATrp)] microspheres as an affinity sorbent for the SPE (solid phase extraction) cleanup of sulfamerazine (SMR) from food samples of animal origin before high performance liquid chromatography (HPLC) analysis. The microspheres were prepared by suspension polymerization of ethylene glycol dimethacrylate (EGDMA) and N-methacryloyl-L-tryptophane methyl ester (MATrp) as a crosslinker and a monomer, respectively. Various parameters affecting the SPE cleanup efficiency of the p(EGDMA-MATrp) microspheres (contact time, pH, initial SMR concentration, ionic strength etc.) were optimized. Under the optimized conditions, maximum adsorption capacity was found to be 8.55 ± 0.44 mg/g sorbent at pH 5.0. 90% of the adsorbed SMR was desorbed by using ACN:MeOH (5:5) mixture as a desorption agent. Applicability of the microspheres for the SPE cleanup of SMR residues in the food samples such as egg and milk with HPLC was also determined. It was demonstrated that the prepared p(EGDMA-MATrp) microspheres could be repeatedly applied for SPE cleanup of sulfamerazine before chromatographic analysis. Also, the recoveries of SMR in milk and egg samples were reasonably satisfactory and in the range of 71 to 90%.
Topics: Adsorption; Animals; Chromatography, Affinity; Chromatography, High Pressure Liquid; Eggs; Hydrogen-Ion Concentration; Kinetics; Methacrylates; Microspheres; Milk; Osmolar Concentration; Polyethylene Glycols; Solid Phase Extraction; Sulfamerazine; Temperature; Tryptophan
PubMed: 30033286
DOI: 10.1016/j.msec.2018.04.058 -
Journal of Chemical Information and... Nov 2019Molecular fingerprints are an efficient and widely used method for similarity-driven virtual screening. Most fingerprint methods can be distinguished by the class of...
Molecular fingerprints are an efficient and widely used method for similarity-driven virtual screening. Most fingerprint methods can be distinguished by the class of structural features considered. The Connected Subgraph Fingerprint (CSFP) overcomes this limitation and regards all structural features of a compound. This results in a more complete feature space and high adaptive potential to certain application scenarios. The novel descriptor surpasses widely used fingerprint methods in some cases and opens the way for topological search in combinatorial fragment spaces.
Topics: Algorithms; Anti-Bacterial Agents; Computer Graphics; Drug Design; Models, Chemical; Molecular Structure; Pharmaceutical Preparations; Sulfamerazine; Sulfonamides
PubMed: 31652055
DOI: 10.1021/acs.jcim.9b00571 -
Chemosphere Jun 2023The removal of antibiotics in wastewater has attracted increasing attention. Herein, a superior photosensitized photocatalytic system was developed with acetophenone...
The removal of antibiotics in wastewater has attracted increasing attention. Herein, a superior photosensitized photocatalytic system was developed with acetophenone (ACP) as the guest photosensitizer, bismuth vanadate (BiVO) as the host catalyst and poly dimethyl diallyl ammonium chloride (PDDA) as the bridging complex, and used for the removal of sulfamerazine (SMR), sulfadiazine (SDZ) and sulfamethazine (SMZ) in water under simulated visible light (λ > 420 nm). The obtained ACP-PDDA-BiVO nanoplates attained a removal efficiency of 88.9%-98.2% for SMR, SDZ and SMZ after 60 min reaction and achieved kinetic rate constant approximately 10, 4.7 and 13 times of BiVO, PDDA-BiVO and ACP-BiVO, respectively, for SMZ degradation. In the guest-host photocatalytic system, ACP photosensitizer was found to have a great superiority in enhancing the light absorption, promoting the surface charge separation-transfer and efficient generation of holes (h) and superoxide radical (·O), greatly contributing to the photoactivity. The SMZ degradation pathways were proposed based on the identified degradation intermediates, involving three main pathways of rearrangement, desulfonation and oxidation. The toxicity of intermediates was evaluated and the results demonstrated that the overall toxicity was reduced compared with parent SMZ. This catalyst maintained 92% photocatalytic oxidation performance after five cyclic experiments and displayed a co-photodegradation ability to others antibiotics (e.g., roxithromycin, ciprofloxacin et al.) in effluent water. Therefore, this work provides a facile photosensitized strategy for developing guest-host photocatalysts, which enabling the simultaneous antibiotics removal and effectively reduce the ecological risks in wastewater.
Topics: Anti-Bacterial Agents; Photolysis; Photosensitizing Agents; Wastewater; Light; Bismuth; Vanadates; Sulfamethazine; Sulfadiazine; Sulfamerazine; Water; Catalysis
PubMed: 36905996
DOI: 10.1016/j.chemosphere.2023.138362 -
The Science of the Total Environment Feb 2021The in-situ advanced anaerobic digestion (AAD) enhanced with zero-valent iron powder (ZVI) under mesophilic condition was investigated to remove 5 antibiotics...
The in-situ advanced anaerobic digestion (AAD) enhanced with zero-valent iron powder (ZVI) under mesophilic condition was investigated to remove 5 antibiotics (sulfamerazine (SMR), sulfamethoxazole (SMZ), ofloxacin (OFL), tetracycline (TC), and roxithromycin (ROX)) and 11 antibiotic resistance genes (ARGs) (AAC (6')-IB-CR, qnrS, ermF, ermT, ermX, sul1, sul2, sul3, tetA, tetB, and tetG) in sewage sludge. The effects of different ZVI dosages, antibiotic concentrations, and solid retention time (SRTs) on the removal were explored. Also, the correlation coefficient of antibiotics and ARGs, microbial community structure, biogas production and methane yield were analyzed. All conducted treatments operated stably, and the modified Gompertz model described the cumulative methane yield well. The antibiotics, with the exception of OFL, were effectively removed in the sewage sludge at a dosage of 1000 mg/L ZVI, SRT 20 d, and an antibiotic concentration of 20 μg/L during AAD. The removal rates of SMZ, SMR, TC, and ROX reached 97.39%, 74.54%, 78.61%, and 56.58%, respectively. AAC (6')-IB-CR and tetB could be effectively reduced during the in-situ AAD. Through the redundancy analysis, AAC (6')-IB-CR, ermT, ermX, sul2, tetB, and tetG had strong positive correlations with the antibiotics in the reactor. The principle component analysis revealed that the community structure was similar when the SRT was 10 d and 20 d at the same amount of ZVI and antibiotic concentrations in the sludge. Under the operating parameters of 1000 mg/L ZVI dosage, SRT 20 d, and an antibiotic concentration of 20 μg/L, Erysipelotrichia, Verrucomicrobia, Clostridia, Caldiserica, and Alphaproteobacteria of the class were dominated microorganisms in the anaerobic digestion.
Topics: Anaerobiosis; Anti-Bacterial Agents; Drug Resistance, Microbial; Iron; Sewage
PubMed: 32911148
DOI: 10.1016/j.scitotenv.2020.142077