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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 -
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 -
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 -
Angewandte Chemie (International Ed. in... Nov 2020The last decade has witnessed a burgeoning of new methods for the enantioselective vicinal difunctionalization of alkenes initiated by electrophilic sulfenyl group... (Review)
Review
The last decade has witnessed a burgeoning of new methods for the enantioselective vicinal difunctionalization of alkenes initiated by electrophilic sulfenyl group transfer. The addition of sulfenium ions to alkenes results in the generation of chiral, non-racemic thiiranium ions. These highly reactive intermediates are susceptible to attack by a myriad of nucleophiles in a stereospecific ring-opening event to afford anti 1,2-sulfenofunctionalized products. The practical application of sulfenium ion transfer has been enabled by advances in the field of Lewis base catalysis. This Review will chronicle the initial discovery and characterization of thiiranium ion intermediates followed by the determination of their configurational stability and the challenges of developing enantioselective variants. Once the framework for the reactivity and stability of thiiranium ions has been established, a critical analysis of pioneering studies will be presented. Finally, a comprehensive discussion of modern synthetic applications will be categorized around the type of nucleophile employed for sulfenofunctionalization.
Topics: Alkenes; Catalysis; Stereoisomerism; Sulfamerazine
PubMed: 32452077
DOI: 10.1002/anie.202005920 -
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 Enzyme Inhibition and... Dec 2020Carbonic anhydrases (CAs) are metalloenzymes responsible for the reversible hydration of carbon dioxide to bicarbonate, a fundamental reaction involved in various...
Carbonic anhydrases (CAs) are metalloenzymes responsible for the reversible hydration of carbon dioxide to bicarbonate, a fundamental reaction involved in various physiological and pathological processes. In the last decades, CAs have been considered as important drug targets for different pathologies such as glaucoma, epilepsy and cancer. The design of potent and selective inhibitors has been an outstanding goal leading to the discovery of new drugs. Among the different strategies developed to date, the design of carbohydrate-based CA inhibitors (CAIs) has emerged as a versatile tool in order to selectively target CAs. The insertion of a glycosyl moiety as a hydrophilic tail in sulfonamide, sulfenamide, sulfamate or coumarin scaffolds allowed the discovery of many different series of sugar-based CAIs, with relevant inhibitory results. This review will focus on carbohydrate-based CAIs developed so far, classifying them in glycosidic and glycoconjugated inhibitors based on the conjugation chemistry adopted.
Topics: Binding Sites; Carbohydrates; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Coumarins; Drug Evaluation, Preclinical; Humans; Hydrophobic and Hydrophilic Interactions; Protein Binding; Structure-Activity Relationship; Sulfamerazine; Sulfonamides; Sulfonic Acids; Triazoles
PubMed: 33078634
DOI: 10.1080/14756366.2020.1825409 -
Journal of Environmental Management Nov 2021In this work the presence of different pharmaceuticals at Doñana National Park (Spain) and their main entry sources (input source or entry points) have been stated over...
In this work the presence of different pharmaceuticals at Doñana National Park (Spain) and their main entry sources (input source or entry points) have been stated over the 2011-2016 years period. Twenty-three selected pharmaceuticals (corresponding to eight therapeutic families) were evaluated in crayfish and water samples from Doñana National Park (Spain) (six sampling points selected in order to cover different possible pollution sources into and surrounding the Park). The multiresidue determination was carried out using enzymatic-microwave assisted extraction prior to high performance liquid chromatography mass spectrometry detection. Sulphonamides (sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole); trimethoprim, an antibiotic that is frequently co-administered with sulfamethoxazole; amphenicols (chloramphenicol, florfenicol and thiamphenicol); fluoroquinolones (ciprofloxacin, enrofloxacin, flumequine, danofloxacin, gatifloxacin, norfloxacin, marbofloxacin and grepafloxacin); penicillins (amoxicillin); tetracyclines (chlortetracycline and oxytetracycline); non-steroidal anti-inflammatory drugs (salicylic acid and ibuprofen); beta-blocker drugs (atenolol); and antiepileptics (carbamazepine) were analysed. Ciprofloxacin, ibuprofen, salicylic acid, flumequine, and carbamazepine were detected and/or quantified at some of the selected sampling points. A clear ecotoxicological risk to the ecosystem was demonstrated from the occurrence of ciprofloxacin in samples obtained after the punctual and massive presence of people inside the Park. Furthermore, flumequine and carbamazepine have been detected in Procambarus clarkii specimens in concentrations around 30 ng g and 14 ng g, respectively, and their occurrence in the specimens could indicate the persistence of the discharge sources. The main source of pharmaceuticals into the Park might be the livestock farming activities, and the influence of urban wastewaters from surrounding villages does not seem to be very important.
Topics: Animals; Astacoidea; Biota; Ecosystem; Environmental Monitoring; Humans; Parks, Recreational; Pharmaceutical Preparations; Spain; Water Pollutants, Chemical
PubMed: 34298344
DOI: 10.1016/j.jenvman.2021.113314 -
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 -
Pharmaceutics May 2022Several literature publications have described the potential application of active pharmaceutical ingredient (API)-polymer phase diagrams to identify appropriate...
Several literature publications have described the potential application of active pharmaceutical ingredient (API)-polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API-polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME. The essence of the HCS is to provide an API risk categorization framework for the development of ASDs via the HME process. The proposed classification system is based on the recognition that the manufacture of crystal-free ASD using the HME process fundamentally depends on the ability of the melt temperature to reach the API's thermodynamic solubility temperature or above. Furthermore, we explored the API-polymer phase diagram as a simple tool for process design space selection pertaining to API or polymer thermal degradation regions and glass transition temperature-related dissolution kinetics limitations. Application of the HCS was demonstrated via HME experiments with two high melting temperature APIs, sulfamerazine and telmisartan, with the polymers Copovidone and Soluplus. Analysis of the resulting ASDs in terms of the residual crystallinity and degradation showed excellent agreement with the preassigned HCS class. Within AbbVie, the HCS concept has been successfully applied to more than 60 different APIs over the last 8 years as a robust validated risk assessment and quality-by-design (QD) tool for the development of HME ASDs.
PubMed: 35631630
DOI: 10.3390/pharmaceutics14051044 -
Molecules (Basel, Switzerland) Jun 2021Rapid chromatographic procedure for quantification of five sulfonamides in medicated feeds are proposed. Satisfactory separation of sulfonamides from medicated feeds was...
Rapid chromatographic procedure for quantification of five sulfonamides in medicated feeds are proposed. Satisfactory separation of sulfonamides from medicated feeds was achieved using a Zorbax Eclipse XDB C18 column (4.6 × 150 mm, 5 µm particle size) with a micellar mobile phase consisting of 0.05 M sodium dodecyl sulphate, 0.02 M phosphate buffer, and 6% propan--ol (pH 3). UV quantitation was set at 260 nm. The proposed procedure allows the determination of sulfaguanidine, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole in medicated feeds for pigs and poultry. Application of the proposed method to the analysis of five pharmaceuticals gave recoveries between 72.7% to 94.7% and coefficients of variations for repeatability and reproducibility between 2.9% to 9.8% respectively, in the range of 200 to 2000 mg/kg sulfonamides in feeds. Limit of detection and limit of quantification were 32.7-56.3 and 54.8-98.4 mg/kg, respectively, depending on the analyte. The proposed procedure for the quantification of sulfonamides is simple, rapid, sensitive, free from interferences and suitable for the routine control of feeds. In the world literature, we did not find the described method of quantitative determination of sulfonamides in medicated feeds with the use of micellar liquid chromatography.
Topics: Animal Feed; Animals; Micelles; Sulfonamides; Swine
PubMed: 34206391
DOI: 10.3390/molecules26133791