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The widespread occurrence of sulfathiazole (STZ) in the environment has raised concerns regarding the potential risks to ecosystem and human health. Thus, there is a need to develop facile and efficient methods for monitoring STZ. In this study, a novel fluorescent probe, based on N, B, F co-doped carbon dots (N, B, F-CDs), was developed for the highly sensitive and selective determination of STZ. The fluorescent N, B, F-CDs were prepared via a one-step hydrothermal method using malonate and 1-allyl-3-vinylimidazolium tetrafluoroborate ionic liquid as precursors. The obtained N, B, F-CDs exhibited excellent fluorescence response toward STZ due to the inner filter effect (IFE), which caused the fluorescence to be quenched. The fluorescent probe allowed the STZ concentration to be accurately determined with a low detection limit of 5.5 ng mL−1 in two wide linear ranges of 0.008–10 μg mL−1 and 10–45 μg mL−1. The practicability of the fluorescent probe was further validated in river water, soil, milk, and egg samples, and the satisfactory spiked recoveries of STZ ranged from 96.1 to 101.6%. The proposed fluorescent probe based on N, B, F-CDs can be easily prepared and possess high selectivity and sensitivity, thereby displaying its tremendous potential for the identification and determination of STZ in the environment.

ISIK, MESUT/0000-0002-4677-8104; Gulcin, ilhami/0000-0001-5993-1668, WOS: 000539602200001, PubMed: 32529657, 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,H-1-NMR (nuclear magnetic resonance),C-13-NMR, and high-resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for alpha-glycosidase (alpha-GLY), human carbonic anhydrase (hCA), and acetylcholinesterase (AChE), withK(I)values in the range of 426.84 +/- 58.42-708.61 +/- 122.67 nM for alpha-GLY, 450.37 +/- 50.35-1,094.34 +/- 111.37 nM forhCA I, 504.37 +/- 57.22-1,205.36 +/- 195.47 nM forhCA 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 againsthCA I,hCA II, and AChE, withK(I)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., Research Fund of Anadolu UniversityAnadolu University [1610S681], Research Fund of Anadolu University, Grant/Award Number: 1610S681

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.

Dual-cloud point extraction (dCPE) was successfully developed for simultaneous extraction of trace sulfonamides (SAs) including sulfamerazine (SMZ), sulfadoxin (SDX), sulfathiazole (STZ) in urine and water samples. Several parameters affecting the extraction were optimized, such as sample pH, concentration of Triton X-114, extraction temperature and time, centrifugation rate and time, back-extraction solution pH, back-extraction temperature and time, back-extraction centrifugation rate and time. High performance liquid chromatography (HPLC) was applied for the SAs analysis. Under the optimum extraction and detection conditions, successful separation of the SAs was achieved within 9 min, and excellent analytical performances were attained. Good linear relationships (R2 ≥ 0.9990) between peak area and concentration for SMZ and STZ were optimized from 0.02 to 10 μg/mL, for SDX from 0.01 to 10 μg/mL. Detection limits of 3.0–6.2 ng/mL were achieved. Satisfactory recoveries ranging from 85 to 108% were determined with urine, lake and tap water spiked at 0.2, 0.5 and 1 μg/mL, respectively, with relative standard deviations (RSDs, n = 6) of 1.5–7.7%. This method was demonstrated to be convenient, rapid, cost-effective and environmentally benign, and could be used as an alternative tool to existing methods for analysing trace residues of SAs in urine and water samples.

Sulfonamides (SAs) are ubiquitous antibiotics that are increasingly detected in the aquatic environment, and may cause potential harm to the environment and humans. Indirect photodegradation has been considered to be a promising natural degradation process for antibiotics in the environment. Chromophoric dissolved organic matter (CDOM) is an important participant in the indirect photodegradation of antibiotics. Indirect photodegradation of sulfathiazole (ST) and sulfamerazine (SM) were studied in the presence of CDOM and marine factors (salinity, pH, nitrate (NO3-) and bicarbonate (HCO3-)) to simulate photodegradation of these compounds in the coastal seawater environment. The main findings are as follows. First, the indirect photodegradation rates of ST and SM in the presence of CDOM were significantly increased and followed the pseudofirst order kinetics. Second, 1O2 played a critical role in the indirect photodegradation of ST and its contribution rate was 54.2%; 3CDOM⁎ performed similarly in the case of SM with a 58.0% contribution rate. Third, CDOM was divided into four fluorescent components by excitation-emission matrix spectroscopy and parallel factor analysis (EEMs-PARAFAC), including three exogenous components and an autochthonous component. The exogenous components with high molecular weight and higher number of aromatic groups played a decisive role in the indirect photodegradation of ST and SM due to their ability to generate higher levels of reactive intermediates (RIs). Finally, seawater factors (salinity, pH, NO3- and HCO3-) influenced the indirect photodegradation of ST and SM by influencing the steady-state concentrations of RIs. This report is the first study of indirect photodegradation of ST and SM from the perspective of the CDOM components and simulated coastal waters.

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.

Pharmaceuticals in the environment are of growing concern for their potential consequences on human and ecosystem health. Alterations in the endocrine system in humans or wildlife are of special interest because these alterations could eventually lead to changes in reproductive fitness. Using the H295R cell line, the potential endocrine disrupting effects of six pharmaceuticals including diclofenac, erythromycin, sulfamethazine, sulfathiazole, oxytetracycline, and chlortetracycline were investigated. After exposure to each target pharmaceutical for 48 h, production of 17beta-estradiol (E2) and testosterone (T), aromatase (CYP19) enzyme activity, or expression of steroidogenic genes were measured. Concentrations of E2 in blood plasma were determined in male Japanese medaka fish after 14 d exposure to sulfathiazole, oxytetracycline, or chlortetracycline. Among the pharmaceuticals studied, sulfathiazole, oxytetracycline and chlortetracycline all significantly affected E2 production by H295R cells. This mechanism of the effect was enhanced aromatase activity and up-regulation of mRNAs for CYP17, CYP19, and 3betaHSD, all of which are important components of steroidogenic pathways. Sulfathiazole was the most potent compound affecting steroidogenesis in H295R cells, followed by chlortetracycline and oxytetracycline. Sulfathiazole significantly increased aromatase activity at 0.2 mg/l. In medaka fish, concentrations of E2 in plasma increased significantly during 14-d exposure to 50 or 500 mg/l sulfathiazole, or 40 mg/l chlortetracycline. Based on the results of this study, certain pharmaceuticals could affect steroidogenic pathway and alter sex hormone balance. Concentrations of the pharmaceuticals studied that have been reported to occur in rivers of Korea are much less than the thresholds for effects on the endpoints studied here. Thus, it is unlikely that these pharmaceuticals are causing adverse effects on fish in those rivers.

Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-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 β-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.

Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and diquat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both sepiapterin reduction and redox cycling. The most potent inhibitors of sepiapterin reduction (IC50s = 31–180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher concentrations of the sulfa drugs (IC50s = 0.37–19.4 μM) were required to inhibit redox cycling, presumably because of distinct mechanisms of sepiapterin reduction and redox cycling. In PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, sulfa drugs inhibited both BH2/BH4 biosynthesis and redox cycling mediated by SPR. Inhibition of BH2/BH4 resulted in decreased production of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxytryptamine. Sulfathiazole (200 μM) markedly suppressed neurotransmitter production, an effect reversed by BH4. These data suggest that SPR and BH4-dependent enzymes, are “off-targets” of sulfa drugs, which may underlie their untoward effects. The ability of the sulfa drugs to inhibit redox cycling may ameliorate ROS-mediated toxicity generated by redox active drugs and chemicals, contributing to their anti-inflammatory activity.

We developed a rapid, microscale and reliable analytical method for binding of drugs to plasma proteins using capillary electrophoresis (CE) with ionic cyclodextrins (CD) combined with frontal analysis. These CDs were used as pseudostationary phases of electrokinetic chromatography (EKC). The CD-modified EKC (CDEKC) approach allowed us to separate anionic drugs from plasma proteins, whereas CZE could not separate these drugs from plasma proteins because they had a similar mobility like plasma proteins. CDs uniquely interact with these drugs but not with plasma proteins. Therefore, CDEKC could be coupled with frontal analysis to measure the binding of anionic drugs to plasma proteins. The binding values obtained by CDEKC were highly consistent with those determined by the ultrafiltration method. Our CDEKC approach should expand the applicability of CE to protein binding analysis.

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.

The ideal therapeutic agent for treatment of osteoarthritis (OA) should have not only potent anti-inflammatory effect but also favorable biological properties to restore cartilage function. Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on OA (Singh et al., 2003) [1]. However, GA has much weaker antioxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel sulfonamido-based gallate named sodium salt of 3,4,5-trihydroxy-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-benzamide (SZNTC) and analyzed its chondro-protective and pharmacological effects. Comparison of SZNTC with GA and sulfathiazole sodium (ST-Na) was also performed. Results showed that SZNTC could effectively inhibit the Interleukin-1 (IL-1)-mediated induction of metalloproteinase-1 (MMP-1) and MMP-3 and could induce the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which demonstrated ability to reduce the progression of OA. SZNTC can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Expression of the collagen I gene was effectively down-regulated, revealing the inhibition of chondrocytes dedifferentiation by SZNTC. Hypertrophy that may lead to chondrocyte ossification was also undetectable in SZNTC groups. The recommended dose of SZNTC ranges from 3.91 μg/ml to 15.64 μg/ml, among which the most profound response was observed with 7.82 μg/ml. In contrast, its source products of GA and ST-Na have a weak effect in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed SZNTC as a promising novel agent in the treatment of chondral and osteochondral lesions.

Metal(II) coordination compounds of a cephalexin Schiff base (HL) derived from the condensation of cephalexin antibiotic with sulphathiazole were synthesized. The Schiff base ligand, mononuclear [ML(OAc)(H2O)2] (M(II)=Mn, Co, Ni, Zn) complexes and magnetically diluted trinuclear copper(II) complex [Cu3L(OH)5] were characterized by several techniques, including elemental and thermal analysis, molar conductance and magnetic susceptibility measurements, electronic, FT-IR, EPR and (1)H NMR spectral studies. The analytical and molar conductance values indicated that the acetate ions coordinate to the metal ions. The Schiff base ligand HL behaves as a monoanionic tridentate NNO and tetradentate NNOO chelating agent in the mono and trinuclear complexes respectively.

A series of Escherichia coli strains were selected for increasing resistance to sulfathiazole. Resistance occurred in seven increments, suggesting the accumulation of several mutations that contributed to overall sulfathiazole resistance. All of the resistant strains had a sulfathiazole-resistant dihydropteroate synthase with a Pro to Ser substitution at amino acid position 64. Overproduction of the wild-type enzyme did not result in sulfathiazole resistance, however overproduction of the mutant enzyme resulted in significant resistance. Conversely, overproduction of the wild-type enzyme in a sulfathiazole-resistant background resulted in a decrease in resistance. Although the specific activity of DHPS in crude extracts was not significantly different from the wild type, the amino acid substitution resulted in an enzyme with a tenfold increase in the Km for p-aminobenzoate, and a 100-fold increase in the Ki for sulfathiazole.

The broad spectrum of the pharmacological effects of sulphonamide family of drugs motivated us to investigate the cellular mechanisms for anti-cancer effects of sulphathiazole and sulphacetamide on T-47D breast cancer cells. Fluorescent microscopy, flow cytometric analysis, caspase-3 activity and DNA fragmentation assays were used to detect apoptosis. The distribution of the cells among different phases of the cell cycle was measured by flow cytometry. The expression of several genes with important roles in some critical cellular pathways including apoptosis, mTOR/AKT pathway and autophagy were determined by real-time RT-PCR analysis. Sulphathiazole and sulphacetamide induced anti-proliferative effects on T-47D cells were independent of apoptosis and cell cycle arrest. The overexpression of critical genes involved in autophagy including ATG5, p53 and DRAM indicated that the main effect of the drug-induced anti-proliferative effects was through induction of autophagy. This process was induced in two different forms, including death inducing and cytoprotective autophagy. Sulphathiazole treatment was followed by higher expression of p53/DRAM and downregulation of Akt/mTOR pathway resulting in death autophagy. In contrast, sulphacetamide treatment lowered expression of p53/DRAM pathway in parallel with upregulation of Akt/mTOR pathway promoting cytoprotective autophagy. The results indicated that autophagy is the main mechanism mediating the anti-cancer effects of sulphathiazole and sulphacetamide on T-47D cells. Alignment of the p53 and DRAM expression along with activation level of Akt survival pathway therefore determines the type of autophagy that occurs.

THE WIDE use of penicillin and the favorable results of its intramuscular injection and in certain cases of its topical application indicated that its local use for sinusitis might prove beneficial. Since December 1944 my colleagues and I have been investigating the effects of penicillin instilled into the maxillary sinus after irrigations in cases both of acute and of chronic infections. Starting with a dilution of 250 units per cubic centimeter, we increased the concentration of penicillin to 500, 1,000, 2,000, 2,500, 5,000 and 10,000 units per cubic centimeter in isotonic solution of sodium chloride without impressive results. At the present time, after irrigation of the antrum and displacement of the isotonic solution of sodium chloride with air, 2 cc. of isotonic solution of sodium chloride containing 10,000 units of penicillin per cubic centimeter is instilled and allowed to remain in the sinus. No evidences of irritation or of sensitivity

IN 1941, Poth and Knotts1 introduced succinylsulfathiazole (sulfasuxidine) as an intestinal antiseptic and bacteriostatic agent. It has proved especially valuable as an adjunct to surgery of the large bowel, as well as in the treatment of certain medical conditions. A further improvement was made in this field with the discovery of phthalylsulfathiazole (sulfathalidine§) by Poth and Ross2 in 1943. This new drug has the advantage of having twice the bacteriostatic activity of succinylsulfathiazole but requiring only half to one third of its dosage. In addition, the drug has not given rise to any toxic reactions such as have occasionally . . .

While good results have been obtained with sulfonamides previously utilized in the intestinal canal, one is constantly on the alert for an agent that may approximate perfection. In recent years sulfaguanidine and succinylsulfathiazole (sulfasuxidine) 1 have been the two agents most widely used in the management of infectious diseases of the colon. Favorable results were obtained in a large percentage of patients treated with the two sulfonamides just mentioned. In the evaluation of sulfaguanidine it is my experience that this agent is more toxic than succinylsulfathiazole, that larger dosages are required for optimum results and that the blood concentration determinations reach a higher level. Succinylsulfathiazole, on the other hand, is apparently less toxic and, while large doses have been prescribed orally, the blood levels range between 1 and 1.5 mg. per hundred cubic centimeters of blood irrespective of the duration of administration of the drug, thus indicating that the absorption

A case of fixed bullous eruption following sulfathiazole therapy is reported, with results of some allergic studies. Only one reference 1 can be found to a case of a similar nature, and at present this article is unavailable to us. REPORT OF A CASE G. S., a Negro aged 33, appeared at the dermatologic outpatient department of the University Hospital on June 16, 1943, with ten to fifteen bullous lesions of two weeks' duration on the mouth, penis, trunk and extremities. These bullae varied from 1 to 4 cm. in diameter and were filled with a clear fluid. He stated that seventeen years previously he had suffered from an attack of gonorrhea. Four years before this admission he experienced another attack of the same disease, which was treated by his own physician with sulfanilamide over a period of four months. Three months prior to this admission, because