-
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 -
British Medical Journal Dec 1975
Review
Topics: Colon; Drug Combinations; Drug Therapy; Endocarditis, Bacterial; Gas Gangrene; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Neutropenia; Nitrofurantoin; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine; Penicillin Resistance; Preanesthetic Medication; Preventive Medicine; Respiratory Tract Infections; Rheumatic Fever; Sulfadiazine; Sulfamerazine; Sulfathiazoles; Surgical Wound Infection; Urinary Tract Infections
PubMed: 1106812
DOI: 10.1136/bmj.4.5996.561 -
The Cochrane Database of Systematic... May 2016Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce the risk of permanent visual loss, recurrent retinochoroiditis, and the severity and duration of acute symptoms. There is uncertainty about the effectiveness of antibiotic treatment.
OBJECTIVES
To compare the effects of antibiotic treatment versus placebo or no treatment for toxoplasma retinochoroiditis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2016, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2016), EMBASE (January 1980 to February 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 February 2016. We searched the reference lists of identified articles and contacted pharmaceutical companies for unpublished trials.
SELECTION CRITERIA
We included randomised controlled trials that compared any antibiotic treatment against placebo or no treatment. We excluded trials that included immunocompromised participants. We considered any antibiotic treatment known to be active against Toxoplasma gondii. Antibiotic treatment could be given in any dose orally, by intramuscular injection, by intravenous infusion, or by intravitreal injection.
DATA COLLECTION AND ANALYSIS
The primary outcomes for this review were visual acuity at least three months after treatment and risk of recurrent retinochoroiditis. Secondary outcomes were improvement in symptoms and signs of intraocular inflammation, size of lesion, and adverse events. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Four trials that randomised a total of 268 participants met the inclusion criteria. In all four studies antibiotic was administered orally.One study conducted in Brazil in both adults and children compared trimethoprim-sulfamexacocol over 20 months to no treatment and was judged to be at high risk of performance, detection, and attrition bias. The other three studies compared antibiotic treatment to placebo. We judged these three studies to be at a mixture of low or unclear risk of bias due to poor reporting. One study conducted in the US in adults studied pyrimethamine-trisulfapyrimidine for eight weeks; one study conducted in the UK in children and adults evaluated pyrimethamine for four weeks; and one study conducted in Brazil in adults investigated trimethoprim-sulfamethoxazole for 12 months. In the last study, all participants had active retinochoroiditis and were treated with antibiotics for 45 days prior to randomisation to trimethoprim-sulfamethoxazole versus placebo.Only the study in Brazil of trimethoprim-sulfamethoxazole over 12 months, in participants with healed lesions, reported the effect of treatment on visual acuity. People treated with antibiotics may have a similar change in visual acuity compared with people treated with placebo at one year (mean difference -1.00 letters, 95% confidence interval (CI) -7.93 to 5.93 letters; 93 participants; low-quality evidence).Treatment with antibiotics probably reduces the risk of recurrent retinochoroiditis compared with placebo (risk ratio (RR) 0.26, 95% CI 0.11 to 0.63; 227 participants; 3 studies; I(2) = 0%; moderate-quality evidence); similar results were seen for acute and chronic retinochoroiditis.The UK study of pyrimethamine for four weeks reported an improvement in intraocular inflammation in treated compared with control participants (RR 1.76, 95% CI 0.98 to 3.19; 29 participants; low-quality evidence). The study in Brazil of trimethoprim-sulfamethoxazole for 12 months stated that the severity of inflammation was higher in the comparator group when compared to the antibiotic-treated group but did not provide further details. In the US study of pyrimethamine-trisulfapyrimidine for eight weeks intraocular inflammation had almost completely resolved by eight weeks in all participants, however in this study all participants received steroid treatment.Two studies (UK and US studies) reported an increased risk of adverse events in treated participants. These were a fall in haemoglobin, leucocyte, and platelet count, nausea, loss of appetite, rash, and arthralgia.
AUTHORS' CONCLUSIONS
Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. Further trials of people with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effects of antibiotic treatment on visual outcomes.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Child; Chorioretinitis; Drug Combinations; Humans; Pyrimethamine; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Sulfadiazine; Sulfamerazine; Sulfamethazine; Toxoplasmosis, Ocular; Trimethoprim, Sulfamethoxazole Drug Combination; Visual Acuity; Watchful Waiting
PubMed: 27198629
DOI: 10.1002/14651858.CD002218.pub2 -
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 -
Pharmaceuticals (Basel, Switzerland) Nov 2022This study constructs a machine learning method to simultaneously analyze the thermodynamic behavior of many polymer-drug systems. The solubility temperature of...
This study constructs a machine learning method to simultaneously analyze the thermodynamic behavior of many polymer-drug systems. The solubility temperature of Acetaminophen, Celecoxib, Chloramphenicol, D-Mannitol, Felodipine, Ibuprofen, Ibuprofen Sodium, Indomethacin, Itraconazole, Naproxen, Nifedipine, Paracetamol, Sulfadiazine, Sulfadimidine, Sulfamerazine, and Sulfathiazole in 1,3-bis[2-pyrrolidone-1-yl] butane, Polyvinyl Acetate, Polyvinylpyrrolidone (PVP), PVP K12, PVP K15, PVP K17, PVP K25, PVP/VA, PVP/VA 335, PVP/VA 535, PVP/VA 635, PVP/VA 735, Soluplus analyzes from a modeling perspective. The least-squares support vector regression (LS-SVR) designs to approximate the solubility temperature of drugs in polymers from polymer and drug types and drug loading in polymers. The structure of this machine learning model is well-tuned by conducting trial and error on the kernel type (i.e., Gaussian, polynomial, and linear) and methods used for adjusting the LS-SVR coefficients (i.e., leave-one-out and 10-fold cross-validation scenarios). Results of the sensitivity analysis showed that the Gaussian kernel and 10-fold cross-validation is the best candidate for developing an LS-SVR for the given task. The built model yielded results consistent with 278 experimental samples reported in the literature. Indeed, the mean absolute relative deviation percent of 8.35 and 7.25 is achieved in the training and testing stages, respectively. The performance on the largest available dataset confirms its applicability. Such a reliable tool is essential for monitoring polymer-drug systems' stability and deliverability, especially for poorly soluble drugs in polymers, which can be further validated by adopting it to an actual implementation in the future.
PubMed: 36422535
DOI: 10.3390/ph15111405 -
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 -
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 -
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 -
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 -
Heliyon Apr 2019Cobalt (Co(II)) and copper (Cu(II)) complexes of sulfamerazine-salicylaldehyde (SS) ligand intercalated Mg/Al-layered double hydroxide [Co-SS-LDH/Cu-SS-LDH] were...
Cobalt (Co(II)) and copper (Cu(II)) complexes of sulfamerazine-salicylaldehyde (SS) ligand intercalated Mg/Al-layered double hydroxide [Co-SS-LDH/Cu-SS-LDH] were prepared for the antimicrobial application. Sulfamerazine and salicylaldehyde were mixed together and dissolved in methanol for the synthesis of SS ligand and modified further by the complexation with Co(II) and Cu(II) metal ions [Co-SS/Cu-SS]. The delaminating/restacking method was used to intercalate the Mg/Al-NO-LDH with the metal complexed ligands (Co-SS/Cu-SS). The obtained materials were analyzed using different characterization techniques to prove their successful synthesis and preparation. The antibacterial activity of the synthesized Co-SS-LDH/Cu-SS-LDH were checked by the inhibition zone method. The prepared hybrid materials showed good antimicrobial activity against both gram negative () and gram positive () bacteria.
PubMed: 31049432
DOI: 10.1016/j.heliyon.2019.e01521