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1.
Molecules ; 26(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065538

RESUMO

New Co(II), Ni(II), and Cu(II) complexes were synthesized with the Schiff base ligand obtained by the condensation of sulfathiazole with salicylaldehyde. Their characterization was performed by elemental analysis, molar conductance, spectroscopic techniques (IR, diffuse reflectance and UV-Vis-NIR), magnetic moments, thermal analysis, and calorimetry (thermogravimetry/derivative thermogravimetry/differential scanning calorimetry), while their morphological and crystal systems were explained on the basis of powder X-ray diffraction results. The IR data indicated that the Schiff base ligand is tridentate coordinated to the metallic ion with two N atoms from azomethine group and thiazole ring and one O atom from phenolic group. The composition of the complexes was found to be of the [ML2]∙nH2O (M = Co, n = 1.5 (1); M = Ni, n = 1 (2); M = Cu, n = 4.5 (3)) type, having an octahedral geometry for the Co(II) and Ni(II) complexes and a tetragonally distorted octahedral geometry for the Cu(II) complex. The presence of lattice water molecules was confirmed by thermal analysis. XRD analysis evidenced the polycrystalline nature of the powders, with a monoclinic structure. The unit cell volume of the complexes was found to increase in the order of (2) < (1) < (3). SEM evidenced hard agglomerates with micrometric-range sizes for all the investigated samples (ligand and complexes). EDS analysis showed that the N:S and N:M atomic ratios were close to the theoretical ones (1.5 and 6.0, respectively). The geometric and electronic structures of the Schiff base ligand 4-((2-hydroxybenzylidene) amino)-N-(thiazol-2-yl) benzenesulfonamide (HL) was computationally investigated by the density functional theory (DFT) method. The predictive molecular properties of the chemical reactivity of the HL and Cu(II) complex were determined by a DFT calculation. The Schiff base and its metal complexes were tested against some bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis). The results indicated that the antibacterial activity of all metal complexes is better than that of the Schiff base.


Assuntos
Cobalto/química , Cobre/química , Níquel/química , Bases de Schiff/química , Sulfatiazóis/química , Antibacterianos/química , Análise Espectral/métodos
2.
Arch Pharm (Weinheim) ; 353(9): e2000102, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529657

RESUMO

In the present study, a series of eleven novel 1,3-diaryltriazene-substituted sulfathiazole moieties (ST1-11) was synthesized by the reaction of diazonium salt of sulfathiazole with substituted aromatic amines and their chemical structures were characterized by Fourier transform infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, and high-resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for α-glycosidase (α-GLY), human carbonic anhydrase (hCA), and acetylcholinesterase (AChE), with KI values in the range of 426.84 ± 58.42-708.61 ± 122.67 nM for α-GLY, 450.37 ± 50.35-1,094.34 ± 111.37 nM for hCA I, 504.37 ± 57.22-1,205.36 ± 195.47 nM for hCA II, and 68.28 ± 10.26-193.74 ± 19.75 nM for AChE. Among the synthesized novel compounds, several lead compounds were investigated against the tested metabolic enzymes. More specifically, ST11 (4-[3-(perfluorophenyl)triaz-1-en-1-yl]-N-(thiazol-2-yl)benzenesulfonamide) showed a highly efficient inhibition profile against hCA I, hCA II, and AChE, with KI values of 450.37 ± 50.35, 504.37 ± 57.22, and 68.28 ± 10.26 nM, respectively. Due to its significant biological inhibitory potency, this derivative may be considered as an interesting lead compound against these enzymes.


Assuntos
Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Colinesterase/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Sulfatiazóis/farmacologia , Células CACO-2 , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Simulação por Computador , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Sulfatiazóis/síntese química , Sulfatiazóis/química , Triazenos/síntese química , Triazenos/química , Triazenos/farmacologia
3.
Anal Chem ; 88(20): 10111-10117, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27642771

RESUMO

We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC.


Assuntos
Varredura Diferencial de Calorimetria/métodos , Glutaratos/química , Difração de Pó/métodos , Sulfatiazóis/química , Difração de Raios X/métodos , Transição de Fase , Estereoisomerismo , Sulfatiazol , Temperatura
4.
Mol Pharm ; 13(10): 3590-3594, 2016 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-27580175

RESUMO

A new multicomponent solid consisting of an antibacterial (norfloxacin) and an antimicrobial (sulfathiazole) was made and characterized with single crystal X-ray diffraction, PXRD, FTIR, and DSC. The title salt shows enhanced solubility in different pH buffers and improved diffusion as well as release and inhibition of bacterial and fungal species relative to the parent drugs. The enhanced in vitro biological properties of the drug-drug salt hydrate may be attributed to the higher extent of its supersaturation with respect to the individual components, which leads to higher diffusion rates.


Assuntos
Antibacterianos/química , Norfloxacino/química , Sulfatiazóis/química , Varredura Diferencial de Calorimetria , Cristalização , Cristalografia por Raios X , Solubilidade , Sulfatiazol
5.
Bioorg Med Chem Lett ; 26(7): 1685-9, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26923694

RESUMO

Water-soluble prodrug strategy is a practical alternative for improving the drug bioavailability of sparingly-soluble drugs with reduced drug efficacy. Many water-soluble prodrugs of sparingly-soluble drugs, such as the phosphate ester of a drug, have been reported. Recently, we described a novel water-soluble prodrug based on O-N intramolecular acyl migration. However, these prodrug approaches require a hydroxy group in the structure of their drugs, and other prodrug approaches are often restricted by the structure of the parent drugs. To develop prodrugs with no restriction in the structure, we focused on a decomposition reaction of arginine methyl ester. This reaction proceeds at room temperature under neutral conditions, and we applied this reaction to the prodrug strategy for drugs with an amino group. We designed and synthesized novel prodrugs of representative sparingly soluble drugs phenytoin and sulfathiazole. Phenytoin and sulfathiazole were obtained as stable salt that were converted to parent drugs under physiological conditions. Phenytoin prodrug 3 showed a short half-life (t1/2) of 13min, whereas sulfathiazole prodrug 7 had a moderate t1/2 of 40min. Prodrugs 3 and 7 appear to be suitable for use as an injectable formulation and orally administered drug, respectively.


Assuntos
Anti-Infecciosos/química , Anticonvulsivantes/química , Guanidina/química , Fenitoína/química , Pró-Fármacos/química , Sulfatiazóis/química , Anti-Infecciosos/síntese química , Anticonvulsivantes/síntese química , Arginina/análogos & derivados , Arginina/síntese química , Arginina/química , Estabilidade de Medicamentos , Fenitoína/síntese química , Pró-Fármacos/síntese química , Solubilidade , Sulfatiazol , Sulfatiazóis/síntese química , Água/química
6.
Bioorg Med Chem ; 24(5): 1121-31, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26833242

RESUMO

Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their ß-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the ß-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands.


Assuntos
Antibacterianos/farmacologia , Azóis/farmacologia , Bactérias/efeitos dos fármacos , Complexos de Coordenação/farmacologia , beta-Lactamas/farmacologia , Antibacterianos/química , Azóis/química , Infecções Bacterianas/tratamento farmacológico , Complexos de Coordenação/química , Humanos , Ligantes , Testes de Sensibilidade Microbiana , Modelos Moleculares , Bases de Schiff/química , Bases de Schiff/farmacologia , Sulfametoxazol/análogos & derivados , Sulfametoxazol/farmacologia , Sulfatiazol , Sulfatiazóis/química , Sulfatiazóis/farmacologia , beta-Lactamas/química
7.
J Environ Manage ; 166: 466-77, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26560639

RESUMO

Sulfonamides (SAs) are one class of the most widely used antibiotics around the world and have been frequently detected in municipal wastewater and surface water in recent years. Their transformation in waste water treatment plants (WWTP) and in water treatment plants (WTP), as well as, their fate and transport in the aquatic environment are of concern. The reaction of six sulfonamides (sulfamethoxazole, sulfapyridine, sulfamethazine, sulfamerazine, sulfathiazole and sulfadiazine) with free chlorine was investigated at a laboratory scale in order to identify the main chlorination by-products. A previously validated method, liquid chromatography/mass spectrometry, was used to analyse SAs and their chlorination by-products. At room temperature, pH 6-7, reaction times of up to 2 h and an initial concentration of 2 mg/L of free chlorine, the majority of SAs suffered degradation of around 65%, with the exception of sulfamethoxazole and sulfathiazole (20%). The main reaction of SAs with free chlorine occurred in the first minute.


Assuntos
Antibacterianos/química , Cloro/química , Cromatografia Líquida/métodos , Sulfonamidas/química , Espectrometria de Massas em Tandem/métodos , Poluentes Químicos da Água/química , Cromatografia Líquida de Alta Pressão/métodos , Halogenação , Concentração de Íons de Hidrogênio , Oxirredução , Sulfametazina/química , Sulfatiazol , Sulfatiazóis/química , Temperatura , Águas Residuárias/química , Purificação da Água/métodos
8.
Water Sci Technol ; 71(3): 412-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25714641

RESUMO

This study used Na2S2O8, NaBrO8 and H2O2to degrade sulfadiazine (SDZ), sulfamethizole (SFZ), sulfamethoxazole (SMX) and sulfathiazole (STZ) under ultraviolet (UV) irradiation. The initial concentration of sulfonamide and oxidant in all experiments was 20 mg/L and 5 mM, respectively. The degradation rate for sulfonamides satisfies pseudo-first-order kinetics in all UV/oxidant systems. The highest degradation rate for SDZ, SFZ, SMX and STZ was in the UV/Na2S2O8, UV/NaBrO3, UV/Na2S2O8 and UV/H2O2 system, respectively. In the UV/Na2S2O8 system, the photodegradation rate of SDZ, SFZ, SMX and STZ was 0.0245 min⁻¹, 0.0096 min⁻¹, 0.0283 min⁻¹ and 0.0141 min⁻¹, respectively; moreover, for the total organic carbon removal rate for SDZ, SFZ, SMX and STZ it was 0.0057 min⁻¹, 0.0081 min⁻¹, 0.0130 min⁻¹ and 0.0106 min⁻¹, respectively. Experimental results indicate that the ability of oxidants to degrade sulfonamide varied with pollutant type. Moreover, UV/Na2S2O8 had the highest mineralization rate for all tested sulfonamides.


Assuntos
Antibacterianos/química , Peróxido de Hidrogênio/química , Fotólise , Poluentes Químicos da Água/química , Cinética , Estrutura Molecular , Oxidantes , Sulfadiazina/química , Sulfametizol/química , Sulfametoxazol/química , Sulfatiazol , Sulfatiazóis/química , Raios Ultravioleta
9.
Artigo em Inglês | MEDLINE | ID: mdl-24521411

RESUMO

This article presents experimental results on 47 µmol L(-1) sulfathiazole (STZ) degradation by Fenton and photo-Fenton reactions using multivariate analysis. The optimal experimental conditions for reactions were obtained by Response Surface Methodology (RSM). In the case of the Fenton reactions there were 192 µmol L(-1) ferrous ions (Fe(II)) and 1856 µmol L(-1) hydrogen peroxide (H2O2), as compared with 157 µmol L(-1) (Fe(II)) and 1219 µmol L(-1) (H2O2) for photo-Fenton reactions. Under these conditions, around 90% of STZ degradation were achieved after 8 minutes treatment by Fenton and photo-Fenton reactions, respectively. Moreover, a marked difference was observed in the total organic carbon (TOC) removal after 60-min treatment, achieving 30% and 75% for the Fenton and photo-Fenton reactions, respectively. Acetic, maleic, succinic and oxamic acids could be identified as main Fenton oxidation intermediates. A similar pattern was found in the case of photo-Fenton reaction, including the presence of oxalic acid and ammonia at short periods of irradiation with UV-A. The calculated values of Average Oxidation State (AOS) corroborate the formation of oxidized products from the initial steps of the reaction.


Assuntos
Peróxido de Hidrogênio/química , Ferro/química , Sulfatiazóis/química , Amônia/análise , Carbono/análise , Cinética , Modelos Químicos , Análise Multivariada , Ácido Oxálico/análise , Oxirredução , Fotoquímica/métodos , Sulfatiazol
10.
Yao Xue Xue Bao ; 49(5): 632-8, 2014 May.
Artigo em Zh | MEDLINE | ID: mdl-25151733

RESUMO

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.


Assuntos
Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Sulfatiazóis/farmacologia , Humanos , Relação Estrutura-Atividade , Sulfatiazol , Sulfatiazóis/química
11.
Environ Pollut ; 350: 124039, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38670426

RESUMO

Although various activated sodium hypochlorite (NaClO) systems were proven to be promising strategies for recalcitrant organics treatment, the direct interaction between NaClO and pollutants without explicit activation is quite limited. In this work, a revolutionary approach to degrade sulfathiazole (STZ) in aqueous and soil slurry by single NaClO without any activator was proposed. The results demonstrated that 100% and 94.11% of STZ could be degraded by 0.025 mM and 5 mM NaClO in water and soil slurry, respectively. The elimination of STZ was shown to involve superoxide anion (O2•-), chlorine oxygen radical (ClO•), and hydroxyl radical (•OH), according to quenching experiments and the analysis of electron paramagnetic resonance. The addition of Cl-, HCO3-, SO42-, and humic acid (HA) marginally impeded the decomposition of STZ, while NO3-, Fe3+, and Mn2+ facilitated the process. The NaClO process exhibited significant removal effectiveness at a neutral initial pH. Moreover, the NaClO facilitated application in various soil samples and water matrices, and the procedure was also successful in effectively eliminating a range of sulfonamides. The suggested NaClO degradation mechanism of STZ was based on the observed intermediates, and the majority of the products exhibited lower ecotoxicity than STZ. Besides, the experiment results by using X-ray diffraction (XRD) and a fourier transform infrared spectrometer (FTIR) indicated the negligible effects on the composition and structure of soil by the treatment of NaClO. Simultaneously, the experimental results also illustrated that the bioavailability of heavy metals and the physiochemical characteristics of the soil before and after the remediation did not change to a significant extent. Following the remediation of NaClO, the phytotoxicity tests showed reduced toxicity to wheat and cucumber seeds. As a result, treating soil and water contaminated with STZ by using NaClO was a reasonably practical and eco-friendly method.


Assuntos
Poluentes do Solo , Solo , Sulfatiazol , Solo/química , Poluentes do Solo/química , Sulfatiazol/química , Poluentes Químicos da Água/química , Sulfatiazóis/química , Ácido Hipocloroso/química , Hipoclorito de Sódio/química , Substâncias Húmicas
12.
Bioorg Med Chem Lett ; 23(8): 2313-8, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23499238

RESUMO

Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14-16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2 µM and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Sulfatiazóis/química , Sulfatiazóis/farmacologia , Animais , Modelos Animais de Doenças , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Humanos , Insulina/metabolismo , Resistência à Insulina , Camundongos , Modelos Moleculares , Conformação Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Proteínas Recombinantes/química , Relação Estrutura-Atividade , Sulfatiazóis/síntese química
13.
Drug Dev Ind Pharm ; 39(10): 1562-72, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23030270

RESUMO

The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.


Assuntos
Anti-Infecciosos/química , Excipientes/química , Modelos Químicos , Dodecilsulfato de Sódio/química , Sulfatiazóis/química , Tensoativos/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Emulsões , Cinética , Micelas , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfatiazol , Comprimidos
14.
AAPS PharmSciTech ; 14(2): 620-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23494469

RESUMO

Colloidal solid dispersion is an innovative breakthrough in the pharmaceutical industry that overcomes the solubility-related issue of poorly soluble drugs by using an amorphous approach and also the stability-related issue by means of a complex formation phenomenon using different carrier materials. In the present study, a newly developed adsorption method is introduced to incorporate a high-energy sulfathiazole-polyvinylpyrrolidone (Plasdone® K-29/32) solid dispersion on porous silicon dioxide (Syloid® 244FP). Different ternary systems of sulfathiazole-Plasdone® K-29/32-Syloid® 244FP were prepared (1:1:2, 1:1:3, and 1:2:2) and categorized depending on the mechanism by which Syloid® 244FP was incorporated. Modulated differential scanning calorimetry (MDSC), X-ray diffraction, Fourier transform infrared spectroscopy, and in vitro dissolution studies were conducted to characterize the ternary systems. The X-ray diffraction and MDSC data showed a lack of crystallinity in all internal and external ternary systems, suggesting a loss of the crystallinity of sulfathiazole compared to the physical mixtures. USP apparatus II was used to measure the in vitro dissolution rate of the prepared systems at 75 rpm in different media. The dissolution rate of the optimum ratio (1:2:2) containing an internal ternary solid dispersion system was found to be three times higher than that of the external and physical systems. Thus, the porous silicon dioxide incorporated into the conventional binary solid dispersion acted as a carrier to disperse the complex and increase the dissolution rate.


Assuntos
Portadores de Fármacos , Povidona/química , Dióxido de Silício/química , Sulfatiazóis/química , Adsorção , Varredura Diferencial de Calorimetria , Química Farmacêutica , Coloides , Cristalografia por Raios X , Estabilidade de Medicamentos , Cinética , Porosidade , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfatiazol , Tecnologia Farmacêutica/métodos
15.
Environ Sci Technol ; 46(4): 2102-11, 2012 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-22260423

RESUMO

The mechanism of covalent bond formation of the model sulfonamide sulfathiazole (STZ) and the stronger nucleophile para-ethoxyaniline was studied in reactions with model humic acid constituents (quinones and other carbonyl compounds) in the absence and presence of laccase. As revealed by high resolution mass spectrometry, the initial bonding of STZ occurred by 1,2- and 1,4-nucleophilic additions of the aromatic amino group to quinones resulting in imine and anilinoquinone formation, respectively. Experiments using the radical scavenger tert-butyl-alcohol provided the same products and similar formation rates as those without scavenger indicating that probably not radical coupling reactions were responsible for the initial covalent bond formation. No addition with nonquinone carbonyl compounds occurred within 76 days except for a slow 1,4-addition to the ß-unsaturated carbonyl 1-penten-3-one. The stability of covalent bonds against desorption and pressurized liquid extraction (PLE) was assessed. The recovery rates showed no systematic differences in STZ extractability between the two product types. This suggests that the strength of bonding is not controlled by the initial type of bond, but by the extent of subsequent incorporation of the reaction product into the formed polymer. This incorporation was monitored for (15)N aniline by (1)H-(15)N HMBC NMR spectroscopy. The initial 1,2- and 1,4-addition bonds were replaced by stronger heterocyclic forms with increasing incubation time. These processes could also hold true for soils, and a slow nonextractable residue formation with time could be related to a slow increase of the amount of covalently bound sulfonamide and the strength of bonding.


Assuntos
Anti-Infecciosos/química , Substâncias Húmicas , Sulfatiazóis/química , Compostos de Anilina/química , Cinética , Lacase/química , Oxirredução , Fenetidina/química , Fenóis/química , Quinonas/química , Sulfatiazol
16.
Water Sci Technol ; 66(7): 1519-26, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22864439

RESUMO

The feasibility of anaerobic ammonium oxidation (anammox) process to treat wastewaters containing antibiotics and heavy metals (such as the liquid fraction of the anaerobically digested swine manure) was studied in this work. The specific anammox activity (SAA) was evaluated by means of manometric batch tests. The effects of oxytetracycline, sulfathiazole, copper and zinc were studied. The experimental data of the short-term assays were fitted with an inhibition model to identify the half maximal inhibitory concentration (IC(50)). After 24 h exposures, IC(50)-values equal to 1.9, 3.9, 650 and 1,100 mg L(-1) were identified for copper, zinc, sulfathiazole and tetracycline respectively. The effect of prolonged exposure (14 days) to oxytetracycline and sulfathiazole was studied by means of repeated batch-assays. Anabolism and catabolism reactions were active during the inhibition tests indicating that anammox bacteria could grow even in the extreme conditions tested. Considering the average concentrations expected in swine wastewaters, the inhibitors studied do not seem to represent a problem for the application of the anammox process. However, in order to verify the effect of these compounds on the growth of anammox bacteria, continuous culture experiments could be conducted.


Assuntos
Antibacterianos/química , Metais Pesados/química , Compostos de Amônio Quaternário/química , Animais , Cobre/química , Oxirredução , Sulfatiazol , Sulfatiazóis/química , Suínos , Tetraciclina/química , Eliminação de Resíduos Líquidos , Zinco/química
17.
AAPS PharmSciTech ; 13(2): 647-60, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22549223

RESUMO

Solid-state characterisation of a drug following pharmaceutical processing and upon storage is fundamental to successful dosage form development. The aim of the study was to investigate the effects of using different solvents, feed concentrations and spray drier configuration on the solid-state nature of the highly polymorphic model drug, sulfathiazole (ST) and its sodium salt (STNa). The drugs were spray-dried from ethanol, acetone and mixtures of these organic solvents with water. Additionally, STNa was spray-dried from pure water. The physicochemical properties including the physical stability of the spray-dried powders were compared to the unprocessed materials. Spray drying of ST from either acetonic or ethanolic solutions with the spray drier operating in a closed cycle mode yielded crystalline powders. In contrast, the powders obtained from ethanolic solutions with the spray drier operating in an open cycle mode were amorphous. Amorphous ST crystallised to pure form I at ≤35 % relative humidity (RH) or to polymorphic mixtures at higher RH values. The usual crystal habit of form I is needle-like, but spherical particles of this polymorph were generated by spray drying. STNa solutions resulted in an amorphous material upon processing, regardless of the solvent and the spray drier configuration employed. Moisture induced crystallisation of amorphous STNa to a sesquihydrate, whilst crystallisation upon heating gave rise to a new anhydrous polymorph. This study indicated that control of processing and storage parameters can be exploited to produce drugs with a specific/desired solid-state nature.


Assuntos
Anti-Infecciosos/química , Sulfatiazóis/química , Tecnologia Farmacêutica/métodos , Acetona/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cristalização , Cristalografia por Raios X , Armazenamento de Medicamentos , Etanol/química , Umidade , Microscopia Eletrônica de Varredura , Difração de Pó , Pós , Solubilidade , Solventes/química , Sulfatiazol , Água/química
18.
Mol Pharm ; 8(2): 532-42, 2011 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-21323367

RESUMO

Formulations containing amorphous active pharmaceutical ingredients (APIs) present great potential to overcome problems of limited bioavailability of poorly soluble APIs. In this paper, we directly compare for the first time spray drying and milling as methods to produce amorphous dispersions for two binary systems (poorly soluble API)/excipient: sulfathiazole (STZ)/polyvinylpyrrolidone (PVP) and sulfadimidine (SDM)/PVP. The coprocessed mixtures were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and intrinsic dissolution tests. PXRD and DSC confirmed that homogeneous glassy solutions (mixture with a single glass transition) of STZ/PVP were obtained for 0.05 ≤ X(PVP) (PVP weight fraction) < 1 by spray drying and for 0.6 ≤ X(PVP) < 1 by milling (at 400 rpm), and homogeneous glassy solutions of SDM/PVP were obtained for 0 < X(PVP) < 1 by spray drying and for 0.7 ≤ X(PVP) < 1 by milling. For these amorphous composites, the value of T(g) for a particular API/PVP ratio did not depend on the processing technique used. Variation of T(g) versus concentration of PVP was monotonic for all the systems and matched values predicted by the Gordon-Taylor equation indicating that there are no strong interactions between the drugs and PVP. The fact that amorphous SDM can be obtained on spray drying but not amorphous STZ could not be anticipated from the thermodynamic driving force of crystallization, but may be due to the lower molecular mobility of amorphous SDM compared to amorphous STZ. The solubility of the crystalline APIs in PVP was determined and the activities of the two APIs were fitted to the Flory-Huggins model. Comparable values of the Flory-Huggins interaction parameter (χ) were determined for the two systems (χ = -1.8 for SDM, χ = -1.5 for STZ) indicating that the two APIs have similar miscibility with PVP. Zones of stability and instability of the amorphous dispersions as a function of composition and temperature were obtained from the Flory-Huggins theory and the Gordon-Taylor equation and were found to be comparable for the two APIs. Intrinsic dissolution studies in aqueous media revealed that dissolution rates increased in the following order: physical mix of unprocessed materials < physical mix of processed material < coprocessed materials. This last result showed that production of amorphous dispersions by co-milling can significantly enhance the dissolution of poorly soluble drugs to a similar magnitude as co-spray dried systems.


Assuntos
Dessecação , Composição de Medicamentos , Polímeros/química , Povidona/química , Sulfametazina/química , Sulfatiazóis/química , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Excipientes/química , Excipientes/metabolismo , Polímeros/metabolismo , Povidona/metabolismo , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfametazina/metabolismo , Sulfatiazol , Sulfatiazóis/metabolismo , Termodinâmica , Difração de Raios X
19.
Food Chem ; 332: 127376, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615382

RESUMO

In this work, a molecularly imprinted sensor employing copper sulfide (CuS) as a novel signal probe was successfully developed for ultrasensitive and selective determination of sulfathiazole (STZ). The reduction signals of Cu2+ produced in the process of electron transfer of CuS containing large amounts of Cu2+ are easy to be captured, which provide high electrochemical signals. Moreover, gold nanoparticles@covalent organic framework with excellent conductivity was introduced on the electrode surface for signal amplification and facilitating electron transfer processes of CuS. Under optimized testing conditions, the proposed sensor offered a linear DPV response to STZ over a very wide concentration range (1.0 × 10-4 to 1.0 × 10-11 mol L-1), with a limit of detection of 4.3 × 10-12 mol L-1. Fodder and mutton samples spiked with STZ were analyzed using this sensor, and the satisfactory recoveries ranging from 83.0% to 107.2% were obtained. In addition, the proposed sensor was used to determine the concentration of STZ in chicken liver and pork liver, with quantification results being near identical to those determined by high-performance liquid chromatography.


Assuntos
Cobre/química , Eletroquímica/instrumentação , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Impressão Molecular , Sulfatiazóis/análise , Eletrodos , Sulfatiazóis/química
20.
Water Res ; 131: 205-207, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29289921

RESUMO

Recent efforts have employed antimicrobial susceptibility assays to describe the residual antimicrobial activity of antibiotics and their transformation products in a variety of environmental processes. Some authors have evaluated the results of these assays using the minimum inhibitory concentration (MIC); however, this approach has fundamental weaknesses. To highlight best practices, this comment describes the advantages of using dose-response curves to calculate the half maximal inhibitory concentration (IC50) and the potential impacts of growth media on the antimicrobial activity of sulfonamide antibiotics.


Assuntos
Anti-Infecciosos/química , Fotólise , Sulfatiazóis/química , Luz Solar , Cinética , Poluentes Químicos da Água/análise
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