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The Journal of Organic Chemistry Mar 2017The catalytic, enantioselective, cyclization of phenols with electrophilic sulfenophthalimides onto isolated or conjugated alkenes affords 2,3-disubstituted benzopyrans...
The catalytic, enantioselective, cyclization of phenols with electrophilic sulfenophthalimides onto isolated or conjugated alkenes affords 2,3-disubstituted benzopyrans and benzoxepins. The reaction is catalyzed by a BINAM-based phosphoramide Lewis base catalyst which assists in the highly enantioselective formation of a thiiranium ion intermediate. The influence of nucleophile electron density, alkene substitution pattern, tether length and Lewis base functional groups on the rate, enantio- and site-selectivity for the cyclization is investigated. The reaction is not affected by the presence of substituents on the phenol ring. In contrast, substitutions around the alkene strongly affect the reaction outcome. Sequential lengthening of the tether results in decreased reactivity, which necessitated increased temperatures for reaction to occur. Sterically bulky aryl groups on the sulfenyl moiety prevented erosion of enantiomeric composition at these elevated temperatures. Alcohols and carboxylic acids preferentially captured thiiranium ions in competition with phenolic hydroxyl groups. An improved method for the selective C(2) allylation of phenols is also described.
Topics: Alkenes; Catalysis; Cyclization; Magnetic Resonance Spectroscopy; Phenols; Stereoisomerism; Sulfamerazine
PubMed: 28257203
DOI: 10.1021/acs.joc.7b00295 -
Oxidative Medicine and Cellular... 2017The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer's disease (AD). The two conditions...
The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer's disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 mol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.
Topics: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase Inhibitors; Diabetes Mellitus, Type 2; Female; GPI-Linked Proteins; Humans; Male; Metformin; Prodrugs; Sulfamerazine
PubMed: 28770024
DOI: 10.1155/2017/7303096 -
Saudi Journal of Biological Sciences May 2021Symbiotic bacteria play vital roles in the survival and health of marine sponges. Sponges harbor rich, diverse and species-specific microbial communities. Symbiotic...
Symbiotic bacteria play vital roles in the survival and health of marine sponges. Sponges harbor rich, diverse and species-specific microbial communities. Symbiotic marine bacteria have increasingly been reported as promising source of bioactive compounds. A culturomics-based study was undertaken to study the diversity of bacteria from marine sponges and their antimicrobial potential. We have collected three sponge samples i.e. , (soft coral) and from north region (Obhur) of Red Sea, Jeddah Saudi Arabia. Total of 144 bacterial strains were isolated from three marine sponges using culture dependent method. Screening of isolated strains showed only 37 (26%) isolates as antagonists against oomycetes pathogens ( and ). Among 37 antagonistic bacteria, only 19 bacterial strains exhibited antibacterial activity against human pathogens (Methicillin-resistant (MRSA) ATCC 43300 ATCC 27853, ATCC 8739, ATCC 29212). Four major classes of bacteria i.e , and were recorded from three marine sponges where was dominant class. One potential bacterial strain sp. EA423 was selected for identification of bioactive metabolites using GC and LC-MS analyses. Bioactive compounds Sulfamerazine, Metronidazole-OH and Ibuprofen are detected from culture extract of strain sp. EA423. Overall, this study gives insight into composition and diversity of antagonistic bacterial community of marine sponges and coral from Red Sea and presence of active metabolites from potential strain. Our results showed that these diverse and potential bacterial communities further need to be studied to exploit their biotechnological significance.
PubMed: 34025160
DOI: 10.1016/j.sjbs.2021.03.042 -
ACS Omega Dec 2023The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a...
Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure-Activity Relationship, Kinetics Mechanism, and In Silico Studies.
The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a dynamic field of study and advancement within medicinal chemistry. This research demonstrates the conjugation of diclofenac and mefenamic acid with sulfa drugs and their screening for urease inhibition. These conjugates' structural confirmation was performed using elemental analysis and spectroscopic methods, including IR, H NMR, and C NMR. Diclofenac conjugated with sulfanilamide (4), sulfacetamide (10), and mefenamic acid conjugated with sulfanilamide (12), and sulfamethoxazole (17) was found potent and demonstrated urease inhibition competitively, with IC (μM) values 3.59 ± 0.07, 5.49 ± 0.34, 7.92 ± 0.27, and 8.35 ± 0.26, respectively. Diclofenac conjugated with sulfathiazole (6), sulfamerazine (8), and sulfaguanidine (11), while mefenamic acid conjugated with sulfisoxazole (13), sulfathiazole (14), and sulfadiazine (15) exhibited a mixed mode of urease inhibition. The IC (μM) values were 16.19 ± 0.21, 9.50 ± 0.28, 4.35 ± 0.23, 15.86 ± 0.25, 14.80 ± 0.27, and 7.92 ± 0.27, respectively. Furthermore, molecular docking studies were employed to predict the binding pose of competitive inhibitors at the urease active site. These conjugates generated stable complexes with the urease protein observed through molecular dynamics (MD) simulations, where no conformational changes occurred throughout the simulations. These results highlight the potential for approved therapeutic molecule conjugates to give rise to new categories of pharmacological agents for urease inhibition. The structural similarity of sulfonamides with urea allows them to compete with urea for binding to the active site of the urease enzyme. Sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) can interact hydrophobically with the active site of the urease enzyme, which may disturb its structure and catalytic activity. Therefore, these conjugates may be helpful in the development of novel pharmacological agents for the treatment of a variety of illnesses in which the urease enzyme is involved.
PubMed: 38075833
DOI: 10.1021/acsomega.3c07275 -
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 -
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 -
Frontiers in Microbiology 2018The microbial communities in freshwater have raised concerns about the ecosystem and human health. Many ecological environmental problems have been found in urban river...
The microbial communities in freshwater have raised concerns about the ecosystem and human health. Many ecological environmental problems have been found in urban river because of the unreasonable use and long-term wastewater discharge. In this study, we explored the bacterial community composition, abundance of 14 antibiotics and 21 antibiotic resistance genes (ARGs), and water environment features in seven water samples and seven sediment samples from Ba River in Xi'an, China. Results showed and were the dominant phyla in all samples, and sediment samples had a higher bacterial diversity and richness than it in water. Bacterial communities of site 5 and 6 were clustered in discrepant patterns compared to those at remaining sites from other samples. It might be influenced by nutrients, heavy metals and antibiotics. Antibiotics concentrations ranged from 1.26 to 1.61 × 10 ng L in water samples and 1.55 to 4.05 × 10 μg kg in sediment samples. Sulfamerazine (SM1) and erythromycin (ERY) were the chief antibiotics in water samples, while the level of oxytetracycline (OTC) and cefazolin (CFZ) were higher in sediment samples. Canonical correspondence analysis showed that trimethoprim (TMP) was significantly related to in W6, and that SM1 and OTC had positive correlation with in W5. The and had higher pollution abundance ranging from 10 to 10 copies/16S rRNA gene copies in all samples. Significant correlations were observed between ARGs and matching antibiotics, suggesting that antibiotics can pose the selective pressure on ARGs in this river. In summary, these finding might provide some new data to the limited information available on the bacterial community characteristics, abundance of antibiotics and ARGs in urban river of China.
PubMed: 30619235
DOI: 10.3389/fmicb.2018.03191 -
Journal of Microencapsulation 2014Polysulfenamides (PSN), with a SN linkage (RSNR2) along the polymer backbone, are a new class of biodegradable and biocompatible polymers. These polymers were unknown...
Polysulfenamides (PSN), with a SN linkage (RSNR2) along the polymer backbone, are a new class of biodegradable and biocompatible polymers. These polymers were unknown prior to 2012 when their synthesis and medicinally relevant properties were reported. The aim of this study was to develop microparticles as a controlled drug delivery system using polysulfenamide as the matrix material. The microparticles were prepared by a water-in-oil-in-water double-emulsion solvent-evaporation method. For producing drug-loaded particles, FITC-dextran was used as a model hydrophilic compound. At the optimal formulation conditions, the external morphology of the PSN microparticles was examined by scanning electron microscopy to show the formation of smooth-surfaced spherical particles with low polydispersity. The microparticles had a net negative surface charge (-23 mV) as analyzed by the zetasizer. The drug encapsulation efficiency of the particles and the drug loading were found to be dependent on the drug molecular weight, amount of FITC-dextran used in fabricating FITC-dextran-loaded microparticles, concentration of PSN and surfactant, and volume of the internal and external water phases. FITC-dextran was found to be distributed throughout the PSN microparticles and was released in an initial burst followed by more continuous release over time. Confocal laser scanning microscopy was used to qualitatively observe the cellular uptake of PSN microparticles and indicated localization of the particles in both the cytoplasm and the nucleus.
Topics: Capsules; Delayed-Action Preparations; Emulsions; HEK293 Cells; Humans; Polymers; Sulfamerazine
PubMed: 23862723
DOI: 10.3109/02652048.2013.814728 -
Journal of the American Chemical Society Oct 2022Sulfoximines are increasingly incorporated in agrochemicals and pharmaceuticals, with the two enantiomers of chiral sulfoximines often having profoundly different...
Sulfoximines are increasingly incorporated in agrochemicals and pharmaceuticals, with the two enantiomers of chiral sulfoximines often having profoundly different binding interactions with biomolecules. Therefore, their application to drug discovery and development requires the challenging preparation of single enantiomers rather than racemic mixtures. Here, we report a general and fundamentally new asymmetric synthesis of sulfoximines. The first -alkylation of sulfenamides, which are readily accessible sulfur compounds with one carbon and one nitrogen substituent, represents the key step. A broad scope for -alkylation was achieved by rhodium-catalyzed coupling with diazo compounds under mild conditions. When a chiral rhodium catalyst was utilized with loadings as low as 0.1 mol %, the -alkylation products were obtained in high yields and with enantiomeric ratios up to 98:2 at the newly generated chiral sulfur center. The -alkylation products were efficiently converted to a variety of sulfoximines with complete retention of stereochemistry. The utility of this approach was further demonstrated by the asymmetric synthesis of a complex sulfoximine agrochemical.
Topics: Agrochemicals; Alkylation; Carbon; Catalysis; Molecular Structure; Nitrogen; Pharmaceutical Preparations; Rhodium; Stereoisomerism; Sulfamerazine; Sulfur
PubMed: 36154032
DOI: 10.1021/jacs.2c09158