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Molecules (Basel, Switzerland) May 2023Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the...
Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the factors responsible for the distribution of sulfonamides in the living organism. Although these drug compounds have been in use for more than half a century, knowledge about their behavior is still limited. Physiological activity is currently attributed to the sulfanyl radical. Our study is devoted to the spectral properties of aqueous solutions of sulfaguanidine, in which the formation of complexes with an H-bond and a protonated form takes place. The nature of the fluorescent state of sulfaguanidine was interpreted using computational chemistry, the electronic absorption method and the luminescence method. The structure of sulfaguanidine includes several active fragments: aniline, sulfonic and guanidine. To reveal the role of fragments in the physiological activity of the studied antibiotic, we calculated and compared the effective charges of the fragments of aniline and sulfaguanidine molecules. Chromophore groups were identified in molecules, which determine the intermolecular interaction between a molecule and a proton-donor solvent. The study also revealed the impact of sulfone and guanidine groups, as well as complexation, on the effective charge of the antibiotic fragment responsible for physiological activity and luminescent ability.
Topics: Sulfaguanidine; Luminescence; Anti-Bacterial Agents; Sulfonamides; Sulfanilamide; Aniline Compounds; Guanidines
PubMed: 37241901
DOI: 10.3390/molecules28104159 -
Antibiotics (Basel, Switzerland) Feb 2021Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide -, pyridine-2-one -, and 2-imino-2-chromene-3-carboxamide , derivatives, were...
Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors.
Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide -, pyridine-2-one -, and 2-imino-2-chromene-3-carboxamide , derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, , , , , , and , revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives , , and demonstrating inhibition of DNA gyrase, with IC values of 18.17-23.87 µM, and of DHFR, with IC values of 4.33-5.54 µM; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, , , and , were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4 and CD8 T lymphocytes. Finally, molecular docking and some AMED studies were performed.
PubMed: 33562582
DOI: 10.3390/antibiotics10020162 -
Journal of Enzyme Inhibition and... Dec 2023Design and synthesis of three novel series of aryl enaminones (- and -) and pyrazole () linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid...
Effect of hydrophobic extension of aryl enaminones and pyrazole-linked compounds combined with sulphonamide, sulfaguanidine, or carboxylic acid functionalities on carbonic anhydrase inhibitory potency and selectivity.
Design and synthesis of three novel series of aryl enaminones (- and -) and pyrazole () linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid functionalities were reported as carbonic anhydrase inhibitors (CAIs) using the "tail approach" strategy in their design to achieve the most variable amino acids in the middle/outer rims of the hCAs active site. The synthesised compounds were assessed for their inhibitory activity against the following human (h) isoforms, hCA I, II, IX, and XII using stopped-flow CO hydrase assay. Enaminone sulphonamide derivatives (-) potently inhibited the target tumour-associated isoforms hCA IX and hCA XII (KIs 26.2-63.7 nM) and hence compounds and were further screened for their cytotoxic activity against MCF-7 and MDA-MB-231 cancer cell lines under normoxic and hypoxic conditions. Derivative showed comparable potency against both MCF-7 and MDA-MB-231 cancer cell lines under both normoxic ((IC = 4.918 and 12.27 µM, respectively) and hypoxic (IC = 1.689 and 5.898 µM, respectively) conditions compared to the reference drug doxorubicin under normoxic (IC = 3.386 and 4.269 µM, respectively) and hypoxic conditions (IC = 1.368 and 2.62 µM, respectively). Cell cycle analysis and Annexin V-FITC and propidium iodide double staining methods were performed to reinforce the assumption that may act as a cytotoxic agent through the induction of apoptosis in MCF-7 cancer cells.
Topics: Humans; Carbonic Anhydrases; Carbonic Anhydrase IX; Sulfaguanidine; Structure-Activity Relationship; Carboxylic Acids; Sulfonamides; Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Pyrazoles; Molecular Structure
PubMed: 37078174
DOI: 10.1080/14756366.2023.2201403 -
Polymers Jan 2022Polymers and their composites have recently attracted attention in both pharmaceutical and biomedical applications. Polyethylene glycol (PEG) is a versatile polymer...
Design, Synthesis and Evaluation of Novel Antimicrobial Polymers Based on the Inclusion of Polyethylene Glycol/TiO Nanocomposites in Cyclodextrin as Drug Carriers for Sulfaguanidine.
Polymers and their composites have recently attracted attention in both pharmaceutical and biomedical applications. Polyethylene glycol (PEG) is a versatile polymer extensively used in medicine. Herein, three novel PEG-based polymers that are pseudopolyrotaxane (PEG/α-CD) (), titania-nanocomposite (PEG/TiONPs) (), and pseudopolyrotaxane-titania-nanocomposite (PEG/α-CD/TiONPs) (), were synthesized and characterized. The chemical structure, surface morphology, and optical properties of the newly materials were examined by FT-IR, H-NMR, SEM, and UV-Vis., respectively. The prepared polymers were used as drug carriers of sulfaguanidine as PEG/α-CD/Drug (), PEG/TiONPs/Drug (), and PEG/α-CD/TiONPs/Drug (). The influence of these drug-carrying formulations on the physical and chemical characteristics of sulfaguanidine including pharmacokinetic response, solubility, and tissue penetration was explored. Evaluation of the antibacterial and antibiofilm effect of sulfaguanidine was tested before and after loading onto the prepared polymers against some Gram-negative and positive bacteria (, , and (MRSA)), as well. The results of this work turned out to be very promising as they confirmed that loading sulfaguanidine to the newly designed polymers not only showed superior antibacterial and antibiofilm efficacy compared to the pure drug, but also modified the properties of the sulfaguanidine drug itself.
PubMed: 35054634
DOI: 10.3390/polym14020227 -
Antimicrobial Agents and Chemotherapy Apr 2018The high acquisition rate of drug resistance by necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for...
The high acquisition rate of drug resistance by necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high-throughput screening of compounds against thiol-deficient strains and subsequent validation with thiol-deficient strains revealed that and mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); and mutants had increased susceptibility to bacitracin (Ba); and , , and mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the levels of thiols and oxidative stress in This study reports the activities of Aza, Su, Fu, and Ba against and provides a rationale for further investigations.
Topics: Antitubercular Agents; Azaguanine; Mutation; Mycobacterium tuberculosis; Oxidative Stress; Sulfaguanidine; Sulfhydryl Compounds
PubMed: 29437626
DOI: 10.1128/AAC.02236-17 -
Crystal Growth & Design Apr 2023Pharmaceutical cocrystals, a type of multicomponent crystalline material incorporating two or more molecular and/or ionic compounds connected by noncovalent interactions...
Pharmaceutical cocrystals, a type of multicomponent crystalline material incorporating two or more molecular and/or ionic compounds connected by noncovalent interactions (such as hydrogen bonds, π-π interactions, and halogen bonds), are attracting increasing attention in crystal engineering. Sulfaguanidine (SGD), one of the most frequently used sulfonamide compounds, was chosen as a model compound in this work to further investigate the hydrogen bond interactions in cocrystals, since it possesses various hydrogen bond donor and acceptor sites. Five cocrystals of SGD, synthesized successfully by slurry and slow evaporation methods, were fully characterized by thermal analysis, X-ray techniques, and Fourier transform infrared spectroscopy. To gain insight into the nature of hydrogen-bonding interactions, theoretical calculations including the analysis of Hirshfeld surface, MEPS (molecular electrostatic potential surface), and QTAIM (quantum theory of atoms in molecules) were conducted. The results are a part of a systematic study of cocrystals of sulfonamides that aims to establish synthon hierarchies in cocrystals containing molecules with multiple hydrogen-bonding functional groups.
PubMed: 37038403
DOI: 10.1021/acs.cgd.2c01337 -
Crystal Growth & Design Feb 2024A thorough re-examination of sulfaguanidine's (SGD) solid-state behavior was conducted, 65 years after the initial report on SGD polymorphism. This investigation focuses...
A thorough re-examination of sulfaguanidine's (SGD) solid-state behavior was conducted, 65 years after the initial report on SGD polymorphism. This investigation focuses on the polymorphic nature of the compound, the formation of hydrates and solvates, and the pivotal role of experimental and computational methods in screening, assessing stability, and understanding transformation processes. The findings confirm the presence of five anhydrates (-), two monohydrate polymorphs ( and ), and nine solvates (with , , , , , , , , and ). Notably, nine novel structures-two anhydrates and seven solvates-are reported, solved from powder X-ray diffraction data. Calorimetric measurements have revealed that is the thermodynamically stable polymorph at room and low temperatures. In contrast, emerges as the stable polymorph at higher temperatures, yet it exhibits remarkable kinetic stability at RT and demonstrates greater stability in terms of hydration. The anhydrate forms exhibit distinctive packing arrangements, while the two hydrates share a close structural resemblance. Among the seven structurally characterized solvates, only the tetrahydrofuran and dimethyl sulfoxide solvates are isostructural. Controlled desolvation experiments enabled the formation of , , and, notably, for the first time. The anhydrate and monohydrate crystal structure prediction studies reveal that the computed lowest-energy structures correspond to experimentally observed forms and propose models for the elusive structure. Overall, the exploration of SGD's solid-state landscape confirms a rich array of highly stable H-bonding motifs and packing arrangements, positioning this study as an ideal model for complex solid-state systems and shedding light on its intricate solid-state nature.
PubMed: 38344672
DOI: 10.1021/acs.cgd.3c01384 -
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 -
RSC Advances Jul 2019A novel sulfaguanidine (SG)-modified polyamide thin-film composite (TFC) nanofiltration (NF) membrane was constructed by the strategy referred to as co-solvent assisted...
A novel sulfaguanidine (SG)-modified polyamide thin-film composite (TFC) nanofiltration (NF) membrane was constructed by the strategy referred to as co-solvent assisted interfacial polymerization (CASIP), which involves the respective interfacial polymerization (IP) of piperazine (PIP) and SG with trimesoyl chloride (TMC) on porous polysulfone (PSf) supports. CASIP enables the formation of a defect-free thin dense active layer and favors higher water permeance up to 79.0 L m h with rejection above 98.3% for NaSO. The resulting PA membrane also demonstrates a high flux recovery ratio of nearly 98.9% to bovine serum albumin protein after being cleaned. More importantly, the current membrane shows excellent anti-adhesive and antimicrobial performances against Gram-negative , Gram-positive LDS.33 and JFS. This promises great potential application of the PA membrane for practical water/wastewater treatment. The prospect of using the co-solvent mediated SG-modified layer as a next-generation anti-fouling/antimicrobial membrane is very encouraging.
PubMed: 35515551
DOI: 10.1039/c9ra03340h