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Sample records for sulfonamides macrolides trimethoprim

  1. Fate of sulfonamides, macrolides, and trimethoprim in different wastewater treatment technologies

    International Nuclear Information System (INIS)

    Goebel, Anke; McArdell, Christa S.; Joss, Adriano; Siegrist, Hansruedi; Giger, Walter

    2007-01-01

    The elimination of sulfonamides, macrolides and trimethoprim from raw wastewater was investigated in several municipal wastewater treatment plants. Primary treatment provided no significant elimination for the investigated substances. Similar eliminations were observed in the secondary treatment of two conventional activated sludge (CAS) systems and a fixed-bed reactor (FBR). Sulfamethoxazole, including the fraction present as N 4 -acetyl-sulfamethoxazole, was eliminated by approximately 60% in comparison to about 80% in a membrane bioreactor (MBR) independently of the solid retention time (SRT), indicating a positive correlation of the observed elimination to the organic substrate concentration. The elimination for macrolides and trimethoprim varied significantly between the different sampling campaigns in the two CAS systems and in the FBR. In the MBR, these analytes were eliminated up to 50% at SRT of 16 ± 2 and 33 ± 3 d. Trimethoprim, clarithromycin and dehydro-erythromycin showed a higher elimination of up to 90% at a SRT of 60-80 d indicating a correlation with reduced substrate loading (SL). Together with the high SRT, the SL may lead to an increased biodiversity of the active biomass, resulting in a broader range of degradation pathways available. Two investigated sand filters showed different elimination behavior. One led to a significant elimination of most macrolides (17-23%) and trimethoprim (74 ± 14%), while no elimination was observed in the other sand filter investigated

  2. Fate of sulfonamides, macrolides, and trimethoprim in different wastewater treatment technologies

    Energy Technology Data Exchange (ETDEWEB)

    Goebel, Anke [Swiss Federal Institute of Aquatic Science and Technology (Eawag), CH-8600 Duebendorf (Switzerland); McArdell, Christa S. [Swiss Federal Institute of Aquatic Science and Technology (Eawag), CH-8600 Duebendorf (Switzerland)]. E-mail: mcardell@eawag.ch; Joss, Adriano [Swiss Federal Institute of Aquatic Science and Technology (Eawag), CH-8600 Duebendorf (Switzerland); Siegrist, Hansruedi [Swiss Federal Institute of Aquatic Science and Technology (Eawag), CH-8600 Duebendorf (Switzerland); Giger, Walter [Swiss Federal Institute of Aquatic Science and Technology (Eawag), CH-8600 Duebendorf (Switzerland)

    2007-01-01

    The elimination of sulfonamides, macrolides and trimethoprim from raw wastewater was investigated in several municipal wastewater treatment plants. Primary treatment provided no significant elimination for the investigated substances. Similar eliminations were observed in the secondary treatment of two conventional activated sludge (CAS) systems and a fixed-bed reactor (FBR). Sulfamethoxazole, including the fraction present as N {sup 4}-acetyl-sulfamethoxazole, was eliminated by approximately 60% in comparison to about 80% in a membrane bioreactor (MBR) independently of the solid retention time (SRT), indicating a positive correlation of the observed elimination to the organic substrate concentration. The elimination for macrolides and trimethoprim varied significantly between the different sampling campaigns in the two CAS systems and in the FBR. In the MBR, these analytes were eliminated up to 50% at SRT of 16 {+-} 2 and 33 {+-} 3 d. Trimethoprim, clarithromycin and dehydro-erythromycin showed a higher elimination of up to 90% at a SRT of 60-80 d indicating a correlation with reduced substrate loading (SL). Together with the high SRT, the SL may lead to an increased biodiversity of the active biomass, resulting in a broader range of degradation pathways available. Two investigated sand filters showed different elimination behavior. One led to a significant elimination of most macrolides (17-23%) and trimethoprim (74 {+-} 14%), while no elimination was observed in the other sand filter investigated.

  3. Resistance to trimethoprim and sulfonamides

    OpenAIRE

    Sköld, Ola

    2001-01-01

    International audience; Sulfonamides and trimethoprim have been used for many decades as efficient and inexpensive antibacterial agents for animals and man. Resistance to both has, however, spread extensively and rapidly. This is mainly due to the horizontal spread of resistance genes, expressing drug-insensitive variants of the target enzymes dihydropteroate synthase and dihydrofolate reductase, for sulfonamide and trimethoprim, respectively. Two genes, sul1 and sul2, mediated by transposons...

  4. Trace analysis of trimethoprim and sulfonamide, macrolide, quinolone, and tetracycline antibiotics in chlorinated drinking water using liquid chromatography electrospray tandem mass spectrometry

    Science.gov (United States)

    Ye, Z.; Weinberg, H.S.; Meyer, M.T.

    2007-01-01

    A multirun analytical method has been developed and validated for trace determination of 24 antibiotics including 7 sulfonamides, 3 macrolides, 7 quinolones, 6 tetracyclines, and trimethoprim in chlorine-disinfected drinking water using a single solid-phase extraction method coupled to liquid chromatography with positive electrospray tandem mass spectrometry detection. The analytes were extracted by a hydrophilic-lipophilic balanced resin and eluted with acidified methanol (0.1% formic acid), resulting in analyte recoveries generally above 90%. The limits of quantitation were mostly below 10 ng/L in drinking water. Since the concentrated sample matrix typically caused ion suppression during electrospray ionization, the method of standard addition was used for quantitation. Chlorine residuals in drinking water can react with some antibiotics, but ascorbic acid was found to be an effective chlorine quenching agent without affecting the analysis and stability of the antibiotics in water. A preliminary occurrence study using this method revealed the presence of some antibiotics in drinking waters, including sulfamethoxazole (3.0-3.4 ng/L), macrolides (1.4-4.9 ng/L), and quinolones (1.2-4.0 ng/L). ?? 2007 American Chemical Society.

  5. Removal and factors influencing removal of sulfonamides and trimethoprim from domestic sewage in constructed wetlands.

    Science.gov (United States)

    Dan A; Yang, Yang; Dai, Yu-nv; Chen, Chun-xing; Wang, Su-yu; Tao, Ran

    2013-10-01

    Twelve pilot-scale constructed wetlands with different configurations were set up in the field to evaluate the removal and factors that influence removal of sulfonamides (sulfadiazine, sulfapyridine, sulfacetamide, sulfamethazine and sulfamethoxazole) and trimethoprim from domestic sewage. The treatments included four flow types, three substrates, two plants and three hydraulic loading rates across two seasons (summer and winter). Most target antibiotics were efficiently removed by specific constructed wetlands; in particular, all types of constructed wetlands performed well for the degradation of sulfapyridine. Flow types were the most important influencing factor in this study, and the best removal of sulfonamides was achieved in vertical subsurface-flow constructed wetlands; however, the opposite phenomenon was found with trimethoprim. Significant relationships were observed between antibiotic degradation and higher temperature and redox potential, which indicated that microbiological pathways were the most probable degradation route for sulfonamides and trimethoprim in constructed wetlands. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Multiresidue determination of fluoroquinolone, sulfonamide, trimethoprim, and chloramphenicol antibiotics in urban waters in China.

    Science.gov (United States)

    Peng, Xianzhi; Tan, Jianhua; Tang, Caiming; Yu, Yiyi; Wang, Zhendi

    2008-01-01

    A feasible method has been optimized to simultaneously determine multiclass antibiotic residues, including sulfonamides, fluoroquinolones, trimethoprim, and chloramphenicol in urban riverine water and wastewater by off-line solid phase extraction and high-performance liquid chromatography coupled with a diode-array ultraviolet detector and a fluorescence detector. Internal standard and standard addition methods were used in combination to identify and quantify these antibiotics to compensate for the matrix interference. The method quantification limits (MQLs) were determined to be 0.035 to 0.100 microg/L and 0.100 to 0.300 microg/L for the riverine water and wastewater, respectively. Recoveries of the investigated antibiotics ranged from 63 to 126%. Sulfamethoxazole was the most frequently detected antibiotic residue in Guangzhou section of the Major Pearl River, South China, with a maximum level of 0.510 microg/L. Fluoroquinolone antibiotics were relatively less detected with a maximum level of 0.459 microg/L. The maximum concentration of sulfamethoxazole reached 5.597 microg/L in the raw wastewater from a large-scale sewage treatment plant in Guangzhou city. Around 30% of sulfamethoxazole might survive the primary clarification and biotreatment processes in the sewage treatment plant. None of the investigated antibiotics have been found above MQLs in the final effluent after chlorine disinfection.

  7. Validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of sulfonamides, trimethoprim and dapsone in muscle, egg, milk and honey.

    Science.gov (United States)

    Varenina, Ivana; Bilandžić, Nina; Kolanović, Božica Solomun; Božić, Đurđica; Sedak, Marija; Đokić, Maja; Varga, Ines

    2016-01-01

    A quantitative multi-residue method that includes 13 sulfonamides, trimethoprim and dapsone was developed and validated according to Commission Decision 2002/657/EC for muscle, milk egg and honey samples. For all matrices, the same extraction procedure was used. Samples were extracted with an acetone/dichloromethane mixture and cleaned up on aromatic sulfonic acid (SO3H) SPE cartridges. After elution and concentration steps, analytes were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data were acquired according to the multiple reaction-monitoring approach (MRM) and analytes were quantified both by the isotope dilution and the matrix-matched approaches calculating the response factors for the scanned product ions. The developed method shows good linearity, specificity, precision (repeatability and within-laboratory reproducibility), and trueness. Estimated CCβ for sulfonamides ranged between 5.6 and 8.2 µg kg(-1) for eggs, between 11.1 and 69.9 µg kg(-1) for milk, between 64.7 and 87.9 µg kg(-1) for muscle, and between 2.7 and 5.3 µg kg(-1) for honey. CCβ values for dapsone were 3.1, 0.6, 0.7 and 1.5 µg kg(-1) and for trimethoprim were 3.1, 6.7, 81.7 and 3.0 µg kg(-1) calculated for eggs, milk, muscle and honey, respectively. Recovery for all matrices was in the range from 89.1% and 109.7%. In matrix effect testing, no significant deviations were found between different samples of muscle and milk; however, a matrix effect was observed when testing different types of honey. The validation results demonstrate that the method is suitable for routine veterinary drug analysis and confirmation of suspect samples.

  8. [Determination of 35 antibiotic residues of tetracyclines, sulfonamides, penicillins, macrolides and amphenicols in milk by liquid chromatography-tandem mass spectromtery].

    Science.gov (United States)

    Wang, Hao; Zhao, Li; Yang, Hongmei; Pan, Hongyan; Shi, Hailiang; Qian, Cong; Zhang, Shan

    2015-09-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the simultaneous determination of 35 antibiotic residues of tetracyclines, sulfonamides, penicillins, macrolides and amphenicols in milk. The samples were extracted with alkaline acetonitrile and McIlvaine buffer solution under ultrasonication. The separation of target compounds was performed on an Eclipse XDB-C, column (150 mm x 2.1 mm, 3.5 µm) with gradient elution at a flow rate of 0.25 mL/min, and with an injection volume of 10 µL. The identification and quantification of the compounds were completed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring ( MRM) mode. The limits of detection were all below 10.0 µg/kg. The average spiked recoveries of the method ranged from 70. 1% to 109. 9% with relative standard deviations (RSDs) of 2.89%-9.99%. After validation, the method was applied to the analysis of antibiotic residues in milk products in China. Fifty samples were screened under the well defined methodology, and the results showed that chloramphenicol, only in one sample, was monitored with the content of 0.48 µg/kg. A risk of contamination of milk with chloramphenicol has been determined to exist. Therefore this method is convenient, rapid, sensitive and reliable, and can be successfully applied to the simultaneous detection of the 35 antibiotic residues of tetracyclines, sulfonamides, penicillins, macrolides and amphenicols in milk.

  9. Multiresidue Method for Quantification of Sulfonamides and Trimethoprim in Tilapia Fillet by Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry Using QuEChERS for Sample Preparation

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    Kátia S. D. Nunes

    2018-01-01

    Full Text Available A multiresidue method for detecting and quantifying sulfonamides (sulfapyridine, sulfamerazine, sulfathiazole, sulfamethazine, sulfadimethoxine, sulfamethoxazole, and sulfamethoxypyridazine and trimethoprim in tilapia fillet (Oreochromis niloticus using liquid chromatography coupled to mass spectrometry was developed and validated. The sample preparation was optimized using the QuEChERS approach. The chromatographic separation was performed using a C18 column and 0.1% formic acid in water and acetonitrile as the mobile phase in the isocratic elution mode. Method validation was performed based on the Commission Decision 2002/657/EC and Brazilian guideline. The validation parameters evaluated were linearity (r ≥ 0.99; limits of detection (LOD and quantification (LOQ, 1 ng·g−1 and 5 ng·g−1, respectively; intraday and interdays precision (CV lower than 19.4%. The decision limit (CCα 102.6–120.0 ng·g−1 and 70 ng·g−1 for sulfonamides and trimethoprim, respectively and detection capability (CCβ 111.7–140.1 ng·g−1 and 89.9 ng·g−1 for sulfonamides and trimethoprim, respectively were determined. Analyses of tilapia fillet samples from fish exposed to sulfamethazine through feed (incurred samples were conducted in order to evaluate the method. This new method was demonstrated to be fast, sensitive, and suitable for monitoring sulfonamides and trimethoprim in tilapia fillet in health surveillance programs, as well as to be used in pharmacokinetics and residue depletion studies.

  10. The influence of salinity on the toxicity of selected sulfonamides and trimethoprim towards the green algae Chlorella vulgaris.

    Science.gov (United States)

    Borecka, Marta; Białk-Bielińska, Anna; Haliński, Łukasz P; Pazdro, Ksenia; Stepnowski, Piotr; Stolte, Stefan

    2016-05-05

    This paper presents the investigation of the influence of salinity variations on the toxicity of sulfapyridine, sulfamethoxazole, sulfadimethoxine and trimethoprim towards the green algae Chlorella vulgaris after exposure times of 48 and 72 h. In freshwater the EC50 values ranged from 0.98 to 123.22 mg L(-1) depending on the compound. The obtained results revealed that sulfamethoxazole and sulfapyridine were the most toxic, while trimethoprim was the least toxic pharmaceutical to the selected organism. Deviations between the nominal and real test concentrations were determined via instrumental analysis to support the interpretation of ecotoxicological data. The toxicity effects were also tested in saline water (3, 6 and 9 PSU). The tendency that the toxicity of selected pharmaceuticals decreases with increasing salinity was observed. Higher salinity implies an elevated concentration of inorganic monovalent cations that are capable of binding with countercharges available on algal surfaces (hydroxyl functional groups). Hence it can reduce the permeability of pharmaceuticals through the algal cell walls, which could be the probable reason for the observed effect. Moreover, for the classification of the mode of toxic action, the toxic ratio concept was applied, which indicated that the effects of the investigated drugs towards algae are caused by the specific mode of toxic action. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Development of a liquid chromatography–tandem mass spectrometry method for the determination of sulfonamides, trimethoprim and dapsone in honey and validation according to Commission Decision 2002/657/EC for banned compounds [corrected].

    Science.gov (United States)

    Economou, Anastasios; Petraki, Olympia; Tsipi, Despina; Botitsi, Eleni

    2012-08-15

    This work reports a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for identification and quantification of seven sulfonamides, trimethoprim and dapsone in honey. The method is based on a solid-phase extraction (SPE) step of the target analytes with Oasis HLB cartridges after acidic hydrolysis of the honey sample to liberate the sugar-bound sulfonamides. Analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the positive electro-spray ionization (ESI) mode with two different isotopically labeled internal standards with the view to improve the quantitative performance of the method. The method validation has been performed according to the Commission Decision 2002/657/EC; the average recoveries, measured at three concentration levels (1.5, 2.5 and 5.0 μg kg(-1)), have been estimated in the range 70 to 106% while the respective % relative standard deviations of the within-laboratory reproducibility ranged from 6 to 18%. Mean values of the expanded uncertainties calculated were in the range 22-41% at the 99% confidence level. Decision limit (CCα) and detection capability (CCβ) values were in the ranges 0.4-0.9 and 0.7-1.4 μg kg(-1), respectively. Matrix effects have been investigated demonstrating a moderate signal suppression/enhancement for most of the target compounds. The method described has been successfully applied to the analysis of honey samples; sulfamethoxazole, sulfathiazole and trimethoprim were detected in some cases. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Iatrogenic, sulfonamide-induced hypothyroid crisis in a Labrador Retriever.

    Science.gov (United States)

    Brenner, K; Harkin, K; Schermerhorn, T

    2009-12-01

    This case report describes a sulfonamide-induced hypothyroid crisis in a 4-year-old Labrador Retriever bitch. Empirical therapy with high-dose trimethoprim-sulfamethoxazole for 10 days produced signs of weakness, ataxia and mental depression and the clinicopathological results supported hypothyroid-induced central nervous system depression. Short-term levothyroxine sodium therapy led to complete resolution of all clinical signs and follow-up thyroid hormone assays ruled out underlying thyroid pathology. This case report is the first to highlight this potentially life-threatening manifestation of sulfonamide-induced hypothyroidism. Sulfonamide combinations are widely used antimicrobials in veterinary medicine and early recognition of this syndrome is critical.

  13. Polymyxin B and Trimethoprim Ophthalmic

    Science.gov (United States)

    Polymyxin B and trimethoprim ophthalmic combination is used to treat bacterial infections of the eye including conjunctivitis (pinkeye; infection ... inside and outer parts of the eyelid). Polymyxin B and trimethoprim are in a class of medications ...

  14. The macrolide antibiotic renaissance.

    Science.gov (United States)

    Dinos, George P

    2017-09-01

    Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently, in order to address increasing antibiotic resistance, a third generation of macrolides displaying improved activity against many macrolide resistant strains was developed. However, these improvements were accompanied with serious side effects, leading to disappointment and causing many researchers to stop working on macrolide derivatives, assuming that this procedure had reached the end. In contrast, a recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolide antibiotics. This chemical synthesis revolution, in combination with reduction in the side effects, namely, 'Ketek effects', has led to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases. © 2017 The British Pharmacological Society.

  15. Naegleria fowleri: trimethoprim sensitivity.

    Science.gov (United States)

    Cerva, L

    1980-09-26

    Trimethoprim in a concentration of 4 micrograms per milliter of Bacto-Casitone (Difco) medium inhibits the growth of nonvirulent Naegleria fowleri isolates. The growth of virulent strains is unaffected even with 400 micrograms of the drug per milliliter of medium. Differences in sensitivity constitute the possibility of a simple selection of environmental isolates. The pathogenicity and virulence of Naegleria species may be connected with the metabolism of folic acid.

  16. Analysis of trimethoprim, lincomycin, sulfadoxin and tylosin in swine manure using laser diode thermal desorption-atmospheric pressure chemical ionization-tandem mass spectrometry.

    Science.gov (United States)

    Solliec, Morgan; Massé, Daniel; Sauvé, Sébastien

    2014-10-01

    A new extraction method coupled to a high throughput sample analysis technique was developed for the determination of four veterinary antibiotics. The analytes belong to different groups of antibiotics such as chemotherapeutics, sulfonamides, lincosamides and macrolides. Trimethoprim (TMP), sulfadoxin (SFX), lincomycin (LCM) and tylosin (TYL) were extracted from lyophilized manure using a sonication extraction. McIlvaine buffer and methanol (MeOH) were used as extraction buffers, followed by cation-exchange solid phase extraction (SPE) for clean-up. Analysis was performed by laser diode thermal desorption-atmospheric pressure chemical-ionization (LDTD-APCI) tandem mass spectrometry (MS/MS) with selected reaction monitoring (SRM) detection. The LDTD is a high throughput sample introduction method that reduces total analysis time to less than 15s per sample, compared to minutes when using traditional liquid chromatography (LC). Various SPE parameters were optimized after sample extraction: the stationary phase, the extraction solvent composition, the quantity of sample extracted and sample pH. LDTD parameters were also optimized: solvent deposition, carrier gas, laser power and corona discharge. The method limit of detection (MLD) ranged from 2.5 to 8.3 µg kg(-1) while the method limit of quantification (MLQ) ranged from 8.3 to 28µgkg(-1). Calibration curves in the manure matrix showed good linearity (R(2)≥ 0.996) for all analytes and the interday and intraday coefficients of variation were below 14%. Recoveries of analytes from manure ranged from 53% to 69%. The method was successfully applied to real manure samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Special Issue: Sulfonamides.

    Science.gov (United States)

    Supuran, Claudiu T

    2017-09-29

    The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a scaffold via a heteroatom, most frequently oxygen or nitrogen (leading thus to sulfamates and sulfamides, respectively) [...].

  18. Special Issue: Sulfonamides

    OpenAIRE

    Claudiu T. Supuran

    2017-01-01

    The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a scaffold via a heteroatom, most frequently oxygen or nitrogen (leading thus to sulfamates and sulfamides, respectively) [...

  19. Genotyping and serotyping of macrolide and multidrug resistant Streptococcus pneumoniae isolated from carrier children

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    S F Swedan

    2016-01-01

    Full Text Available Aims: Streptococcus pneumoniae, an opportunistic pathogen commonly carried asymptomatically in the nasopharynx of children, is associated with increasing rates of treatment failures due to a worldwide increase in drug resistance. We investigated the carriage of S. pneumoniae in children 5 years or younger, the identity of prevalent serotypes, the rates of resistance to macrolides and other antimicrobial agents and the genotypes responsible for macrolide resistance. Materials and Methods: Nasopharyngeal swabs were collected from 157 children under 5 years for cultural isolation of S. pneumoniae. Antibiogram of isolates  was determined using the disk diffusion test, and the minimal inhibitory concentration to macrolides was determined using the E-test. Isolate serotypes and macrolide resistance genes, erm(B and mef(E, were identified using multiplex polymerase chain reactions. Results: S. pneumoniae was recovered from 33.8% of children; 41.9% among males and 21.9% among females (P = 0.009. The highest carriage rate occurred among age groups 7-12 months and 49-60 months. Most frequent serotypes were 19F, 6A/B, 11A, 19A, 14 and 15B/C.  Resistance to macrolides was 60.4%. Resistance to oxacillin, trimethoprim/sulfamethoxazole and clindamycin was present among 90.6%, 54.7% and 32.1% of isolates, respectively. All isolates were susceptible to chloramphenicol, levofloxacin and vancomycin. Isolates resistant to one or more macrolide drugs were more likely to be multidrug resistant. Resistance to clindamycin or oxacillin coexisted with macrolide resistance. Among the erythromycin-resistant isolates, erm(B, mef(E and erm(B and mef(E genes were present at rates of 43.8%, 37.5% and 6.3%, respectively. Erm(B and mef(E were associated with very high level and moderate-to-high level resistance to macrolides, respectively. Conclusion: A significant proportion of children harboured macrolide and multidrug-resistant S. pneumoniae.

  20. Special Issue: Sulfonamides

    Directory of Open Access Journals (Sweden)

    Claudiu T. Supuran

    2017-09-01

    Full Text Available The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A, or appended to such a scaffold via a heteroatom, most frequently oxygen or nitrogen (leading thus to sulfamates and sulfamides, respectively [...

  1. Synthesis of functionalised sulfonamides

    OpenAIRE

    Mok, B. L.

    2008-01-01

    Sulfonamides are important therapeutic agents and have a diverse array of biological functions in biology and medicine. Their means of synthesis has often involved the use of unstable sulfonyl chloride species; however, recent research has established pentafluorophenyl (PFP) sulfonate esters as a useful stable alternative to such species. This thesis describes the use of PFP vinyl sulfonate in a [3+2] cycloaddition with a variety of N-methyl-nitrones, providing access to the corresponding...

  2. Pharmacokinetics of macrolides in foals.

    Science.gov (United States)

    Villarino, N; Martín-Jiménez, T

    2013-02-01

    Macrolides are used for treatment of pneumonia and extrapulmonary conditions caused by Rhodococcus equi. In foals, macrolides have an extraordinary capacity to accumulate in different lung tissue compartments. These drugs show unique pharmacokinetic features such as rapid and extensive distribution and long persistence in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells from foals. This article reviews the pharmacokinetic characteristics of erythromycin, azithromycin, clarithromycin, tulathromycin, telithromycin, gamithromycin, and tilmicosin in foals, with emphasis on PELF and BAL cell concentrations. © 2012 Blackwell Publishing Ltd.

  3. [Tetracyclines, sulfonamides and metronidazole].

    Science.gov (United States)

    Pérez-Trallero, Emilio; Iglesias, Luis

    2003-11-01

    Tetracyclines form a group of natural and semisynthetic products that acts inhibiting the bacterial protein synthesis. They are bacteriostatic agents, exhibiting activity against a wide range of organisms, but they are at the present of limited use because of their acquired resistance. Doxycycline is currently the most frequently used tetracycline in human medicine and it is included in the List of Essential Medicines of the World Health Organization. Sulfonamides are synthetic, broad-spectrum bacteriostatic antibiotics. They were the first effective systemic antimicrobial agents. Their mode of action is based on the inhibition of DNA synthesis. Due to their toxicity and high adquired resistance their use is currently very low. Metronidazole is the main compound of 5-nitroimidazole family. It is a very active bactericidal antibiotic against anaerobic and some microaerophilic bacteria and it is still very useful in the treatment of bacterian and parasitic infections.

  4. In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.

    NARCIS (Netherlands)

    Afeltra, J.; Meis, J.F.G.M.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

    2002-01-01

    The susceptibilities of 70 strains of Aspergillus species were tested against seven different sulfa drugs and pentamidine by a microdilution method with RPMI 1640 and yeast nitrogen base media. Sulfamethoxazole, sulfadiazine, and pentamidine were active in vitro. The MICs obtained with RPMI 1640

  5. Amidine Sulfonamides and Benzene Sulfonamides: Synthesis and Their Biological Evaluation

    OpenAIRE

    Muhammad Abdul Qadir; Mahmood Ahmed; Hina Aslam; Sadia Waseem; Muhammad Imtiaz Shafiq

    2015-01-01

    New amidine and benzene sulfonamide derivatives were developed and structures of the new products were confirmed by elemental and spectral analysis (FT-IR, ESI-MS, 1HNMR, and 13CNMR). In vitro, developed compounds were screened for their antibacterial and antifungal activities against medically important bacterial strains, namely, S. aureus, B. subtilis, and E. coli, and fungi, namely, A. flavus, A. parasiticus, and A. sp. The antibacterial and antifungal activities have been determined by me...

  6. Preparation of sulfonamides from N-silylamines

    OpenAIRE

    Naredla, Rajasekhar Reddy; Klumpp, Douglas A.

    2013-01-01

    Sulfonamides have been prepared in high yields by the reactions of N-silylamines with sulfonyl chlorides and fluorides. In a competition experiment, the sulfonyl chlorides were found to be far more reactive than sulfonyl fluorides. The chemistry may be used to prepare aliphatic, aromatic, tertiary, secondary, and primary sulfonamides. It may also be done in the absence of solvent and the byproduct trimethylsilyl chloride recovered in good yield. Primary sulfonamides were synthesized from the ...

  7. Comparison of multi-sulfonamide biosensor immunoassays

    NARCIS (Netherlands)

    Ploum, M.E.; Korpimaeki, T.; Haasnoot, W.; Kohen, F.

    2005-01-01

    Three different group-specific anti-sulfonamide antibodies were compared in inhibition assay formats in an optical biosensor (BIACORE 3000) using CM5 sensor chips coated with three different sulfonamide derivatives. The antibodies used were an anti-sulfamethazine monoclonal antibody (Mab) 21C7, the

  8. 40 CFR 721.9550 - Sulfonamide.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sulfonamide. 721.9550 Section 721.9550 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9550 Sulfonamide. (a) Chemical substance and...

  9. Macrolides in Chronic Inflammatory Skin Disorders

    Directory of Open Access Journals (Sweden)

    Abdullateef A. Alzolibani

    2012-01-01

    Full Text Available Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents.

  10. [The discovery of hypoglycemic sulfonamides].

    Science.gov (United States)

    Loubatières-Mariani, Marie-Madeleine

    2007-01-01

    In 1933 Auguste Loubatières started to work at the Physiological Laboratory of the Montpellier Medical School, famous for the scientific work of Emmanuel Hédon and then Louis Hédon on experimental diabetes mellitus. Auguste Loubatières was particularly interested in the study of a new preparation of long-lasting insulin (insulin-protamine-zinc: IPZ) in the totally pancreatectomized dog. In 1938, he observed that high doses of IPZ induced a severe and protracted hypoglycemia entailing convulsive attacks and even irreversible coma. The story of hypoglycemic sulfonamides started in France in spring 1942. During the second world war, because of the food shortage in Montpellier, a lot of people ate rotting food or even food contaminated with bacteria, such as shellfish. Many cases of thyphoid fever were diagnosed and treated by Marcel Janbon at the Clinic of the Montpellier Medical School with a new sulfonamide (VK 57 or 2254 RP). Adverse reactions were observed: in some patients, convulsions and even prolonged coma occurred; in some others a major drop in blood glucose was observed. M. Janbon informed the physiologists about these observations questioning them for an interpretation. A. Loubatières was particularly interested and immediately undertook animal trials. On June 13, 1942, he observed that repeated oral administration of 2254 RP in the normal fasting conscious dog induced a progressive, marked and long-lasting decrease in glycemia. He continued his experiments and definitively established the hypoglycemic effect of this sulfonamide. However the mechanism of action remained to be established. The pattern of some graphs reminded him that of some others he could previously observe in the study with IPZ; it occurred to him that 2254 RP could lower the blood glucose concentration by stimulating insulin secretion. He had then to establish the validity of his hypothesis. From 1942 to 1946, A. Loubatières performed a systematic study of the effects of 2254 RP

  11. Evaluation of Veterinary-Specific Interpretive Criteria for Susceptibility Testing of Streptococcus equi Subspecies with Trimethoprim-Sulfamethoxazole and Trimethoprim-Sulfadiazine.

    Science.gov (United States)

    Sadaka, Carmen; Kanellos, Theo; Guardabassi, Luca; Boucher, Joseph; Watts, Jeffrey L

    2017-01-01

    Antimicrobial susceptibility test results for trimethoprim-sulfadiazine with Streptococcus equi subspecies are interpreted based on human data for trimethoprim-sulfamethoxazole. The veterinary-specific data generated in this study support a single breakpoint for testing trimethoprim-sulfamethoxazole and/or trimethoprim-sulfadiazine with S. equi This study indicates trimethoprim-sulfamethoxazole as an acceptable surrogate for trimethoprim-sulfadiazine with S. equi. Copyright © 2016 Sadaka et al.

  12. Evaluation of Veterinary-Specific Interpretive Criteria for Susceptibility Testing of Streptococcus equi Subspecies with Trimethoprim-Sulfamethoxazole and Trimethoprim-Sulfadiazine

    DEFF Research Database (Denmark)

    Sadaka, Carmen; Kanellos, Theo; Guardabassi, Luca

    2017-01-01

    Antimicrobial susceptibility test results for trimethoprim-sulfadiazine with Streptococcus equi subspecies are interpreted based on human data for trimethoprim-sulfamethoxazole. The veterinary-specific data generated in this study support a single breakpoint for testing trimethoprim-sulfamethoxaz......Antimicrobial susceptibility test results for trimethoprim-sulfadiazine with Streptococcus equi subspecies are interpreted based on human data for trimethoprim-sulfamethoxazole. The veterinary-specific data generated in this study support a single breakpoint for testing trimethoprim...

  13. INVESTIGATING ENVIRONMENTAL SINKS OF MACROLIDE ...

    Science.gov (United States)

    Possible environmental sinks (wastewater effluents, biosolids, sediments) of macrolide antibiotics (i.e., azithromycin, roxithromycin and clarithromycin)are investigated using state-of-the-art analytical chemistry techniques. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews

  14. Solid-state interactions between trimethoprim and parabens

    DEFF Research Database (Denmark)

    Pedersen, S.; Kristensen, H. G.; Cornett, Claus

    1994-01-01

    Solid-state interactions between trimethoprim and the esters of 4-hydroxybenzoic acid (parahydroxybenzoates or parabens) used for anti-microbial preservation are investigated. The formation of a crystalline 1/1 molecular compound between trimethoprim and methyl parahydroxybenzoate is demonstrated...... by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and solid-state C-13-NMR. Interactions between trimethoprim and 4-hydroxybenzoic acid and its ethyl,propyl and butyl esters were not observed. The nature of the trimethoprim and methyl parahydroxybenzoate...

  15. Radioenzymatic assay for trimethoprim in very small serum samples

    International Nuclear Information System (INIS)

    Yogev, R.; Melick, C.; Tan-Pong, L.

    1985-01-01

    A modification of the methotrexate radioassay kit (supplied by New England Enzyme Center) enabled determination of trimethoprim levels in 5-microliter serum samples. An excellent correlation between this assay and high-pressure liquid chromatography assay was found. These preliminary results suggest that with this method rapid determination of trimethoprim levels in very small samples (5 to 10 microliters) can be achieved

  16. Solid-state interactions between trimethoprim and parabens

    DEFF Research Database (Denmark)

    Pedersen, S.; Kristensen, H. G.; Cornett, Claus

    1994-01-01

    Solid-state interactions between trimethoprim and the esters of 4-hydroxybenzoic acid (parahydroxybenzoates or parabens) used for anti-microbial preservation are investigated. The formation of a crystalline 1/1 molecular compound between trimethoprim and methyl parahydroxybenzoate is demonstrated...

  17. In vitro Evaluation of Trimethoprim and Sulfamethoxazole from Fixed ...

    African Journals Online (AJOL)

    trimethoprim (TMP) and sulfamethoxazole (SMX) from fixed-dose combination generic products using a flow-through cell technique. Methods: Absorbance measurement was achieved at 247.8 and 257.9 nm for trimethoprim and sulfamethoxazole, respectively. USP Apparatus 4 with 22.6 mm cells, laminar flow at 16 ml/min, ...

  18. Factors that cause trimethoprim resistance in Streptococcus pyogenes.

    Science.gov (United States)

    Bergmann, René; van der Linden, Mark; Chhatwal, Gursharan S; Nitsche-Schmitz, D Patric

    2014-01-01

    The use of trimethoprim in treatment of Streptococcus pyogenes infections has long been discouraged because it has been widely believed that this pathogen is resistant to this antibiotic. To gain more insight into the extent and molecular basis of trimethoprim resistance in S. pyogenes, we tested isolates from India and Germany and sought the factors that conferred the resistance. Resistant isolates were identified in tests for trimethoprim or trimethoprim-sulfamethoxazole (SXT) susceptibility. Resistant isolates were screened for the known horizontally transferable trimethoprim-insensitive dihydrofolate reductase (dfr) genes dfrG, dfrF, dfrA, dfrD, and dfrK. The nucleotide sequence of the intrinsic dfr gene was determined for resistant isolates lacking the horizontally transferable genes. Based on tentative criteria, 69 out of 268 isolates (25.7%) from India were resistant to trimethoprim. Occurring in 42 of the 69 resistant isolates (60.9%), dfrF appeared more frequently than dfrG (23 isolates; 33.3%) in India. The dfrF gene was also present in a collection of SXT-resistant isolates from Germany, in which it was the only detected trimethoprim resistance factor. The dfrF gene caused resistance in 4 out of 5 trimethoprim-resistant isolates from the German collection. An amino acid substitution in the intrinsic dihydrofolate reductase known from trimethoprim-resistant Streptococcus pneumoniae conferred resistance to S. pyogenes isolates of emm type 102.2, which lacked other aforementioned dfr genes. Trimethoprim may be more useful in treatment of S. pyogenes infections than previously thought. However, the factors described herein may lead to the rapid development and spread of resistance of S. pyogenes to this antibiotic agent.

  19. Antimicrobial susceptibility testing of bovine digital dermatitis treponemes identifies macrolides for in vivo efficacy testing.

    Science.gov (United States)

    Evans, N J; Brown, J M; Hartley, C; Smith, R F; Carter, S D

    2012-12-07

    Digital dermatitis (DD) is a major infectious lameness of dairy cattle and sheep considered to be caused by treponemes. The aim of this study was to identify antibiotics effective against DD treponemes that might be useful in the treatment of ruminant DD in the future or to identify antibiotics useful in isolation studies. Here, a microdilution method was used to identify in vitro antimicrobial susceptibility of treponemes cultured from DD lesions to eight relevant antibiotics. DD treponemes exhibited highest susceptibility to amoxicillin, azithromycin and gamithromycin. Unfortunately, amoxicillin whilst having potential for DD treatment in other animals (e.g. sheep) would require milk withhold periods in dairy cattle. DD treponemes were not particularly susceptible to two cephalosporins: cefalexin and ceftiofur, which do not require milk withhold. The bacteria demonstrated low susceptibility to trimethoprim and especially colistin suggesting these antimicrobials may be particularly useful in isolation of DD treponemes. The most promising high susceptibility results for macrolides indicate a rationale to consider veterinary licensed macrolides as DD treatments. Furthermore, given the DD treponeme antibiotic susceptibility similarities to established treatments for human treponematoses, identification of treponemacidal, long acting β-lactam analogues not requiring milk withhold may allow for development of a successful treatment for dairy cattle DD. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 16-membered macrolide antibiotics: a review.

    Science.gov (United States)

    Arsic, Biljana; Barber, Jill; Čikoš, Ana; Mladenovic, Milan; Stankovic, Nevena; Novak, Predrag

    2018-03-01

    The 16-membered macrolide antibiotics (e.g. tylosin A and josamycin) are mainly used in veterinary medicine, and are much less studied than their 14- and 15-membered erythromycin-based cousins. Although these antibiotics have similar antibacterial profiles, with activity primarily against Gram-positive and a limited range of Gram-negative organisms, the 16-membered macrolides show some advantages. These include better gastrointestinal tolerance, lack of drug-drug interactions, and activity against certain resistant bacterial strains by extension of the peptide tunnel reach allowing additional interactions. In addition to antibacterial activity, the most famous representative of the class, tylosin A, as well as some derivatives of desmycosin (tylosin B), have shown antimalarial activity. Such activity has also been observed in the 14-membered macrolide antibiotics, azithromycin, solithromycin and clindamycin. This antimalarial activity provides the opportunity to investigate these drugs as cheap and effective antimalarials. This is an overview of the latest research on biosynthesis, structure, chemical properties and mode of action of 16-membered macrolides, with special emphasis on their most explored members: tylosin A and josamycin. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  1. Amidine Sulfonamides and Benzene Sulfonamides: Synthesis and Their Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Muhammad Abdul Qadir

    2015-01-01

    Full Text Available New amidine and benzene sulfonamide derivatives were developed and structures of the new products were confirmed by elemental and spectral analysis (FT-IR, ESI-MS, 1HNMR, and 13CNMR. In vitro, developed compounds were screened for their antibacterial and antifungal activities against medically important bacterial strains, namely, S. aureus, B. subtilis, and E. coli, and fungi, namely, A. flavus, A. parasiticus, and A. sp. The antibacterial and antifungal activities have been determined by measuring MIC values (μg/mL and zone of inhibitions (mm. Among the tested compounds, it was found that compounds 3b, 9a, and 9b have most potent activity against S. aureus, A. flavus, and A. parasiticus, respectively, and were found to be more active than sulfamethoxazole and itraconazole with MIC values 40 μg/mL. In contrast, all the compounds were totally inactive against the A. sp. except 10b and 15b to show activity to some extent.

  2. Efficient click reaction towards novel sulfonamide hybrids by ...

    Indian Academy of Sciences (India)

    Dong-Jun FU

    2018-02-01

    Feb 1, 2018 ... bCollaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan Province,. China ... Twelve novel sulfonamide hybrids were designed by molecular hybridization strategy. The target ... Molecular hybridization strategy; click reaction; sulfonamide; antiproliferative. 1.

  3. Ecotoxicity evaluation of selected sulfonamides.

    Science.gov (United States)

    Białk-Bielińska, Anna; Stolte, Stefan; Arning, Jürgen; Uebers, Ute; Böschen, Andrea; Stepnowski, Piotr; Matzke, Marianne

    2011-10-01

    Sulfonamides (SAs) are a group of antibiotic drugs widely used in veterinary medicine. The contamination of the environment by these pharmaceuticals has raised concern in recent years. However, knowledge of their (eco)toxicity is still very basic and is restricted to just a few of these substances. Even though their toxicological analysis has been thoroughly performed and ecotoxicological data are available in the literature, a systematic analysis of their ecotoxicological potential has yet to be carried out. To fill this gap, 12 different SAs were chosen for detailed analysis with the focus on different bacteria as well as non-target organisms (algae and plants). A flexible (eco)toxicological test battery was used, including enzymes (acetylcholinesterase and glutathione reductase), luminescent marine bacteria (Vibrio fischeri), soil bacteria (Arthrobacter globiformis), limnic unicellular green algae (Scenedesmus vacuolatus) and duckweed (Lemna minor), in order to take into account both the aquatic and terrestrial compartments of the environment, as well as different trophic levels. It was found that SAs are not only toxic towards green algae (EC₅₀=1.54-32.25 mg L⁻¹) but have even stronger adverse effect on duckweed (EC₅₀=0.02-4.89 mg L⁻¹) than atrazine - herbicide (EC₅₀=2.59 mg L⁻¹). Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Use of sulfonamides in layers in Kampala district, Uganda and ...

    African Journals Online (AJOL)

    Background: Use of antimicrobials like sulfonamides in production of layers is a public health risk since it inevitably results in sulfonamide residues in eggs. The presence of the residues may be influenced by knowledge, attitudes and practices of farmers regarding use of sulfonamides (and other antimicrobials) in poultry.

  5. Flow cytometric immunoassay for sulfonamides in raw milk

    NARCIS (Netherlands)

    Keizer, de W.; Bienenmann-Ploum, M.; Bergwerff, A.A.; Haasnoot, W.

    2008-01-01

    Sulfonamide antibiotics are applied in veterinary medicine for the treatment of microbial infections. For the detection of residues of sulfonamides in milk, a multi-sulfonamide flow cytometric immunoassay (FCI) was developed using the Luminex MultiAnalyte Profiling (xMAP) technology. In this

  6. TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE IN SEWAGE ISOLATES OF ESCHERICHIA COLI

    Science.gov (United States)

    Sewage samples from seven locations in the United States were analyzed for Escherichia coli isolates which were resistant to trimethoprim-sulfamethoxazole (SXT). The prevalence rate of SXT resistant organisms varied between the different geographical locales. The majority of th...

  7. The Effect of Trimethoprim on Serum Folate Levels in Humans

    DEFF Research Database (Denmark)

    Petersen, Kasper Meidahl; Eplov, Kasper; Nielsen, Torben Kjær

    2016-01-01

    allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency......Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim...... on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment...

  8. ENHANCED BIODEGRADATION OF IOPROMIDE AND TRIMETHOPRIM IN NITRIFYING ACTIVATED SLUDGE

    Science.gov (United States)

    Iopromide and trimethoprim are frequently detected pharmaceuticals in effluents of wastewater treatment plants and in surface waters due to their persistence and high usage. Laboratory scale experiments showed that a significantly higher removal rate in nutrifying activated sludg...

  9. Genetic characterization of trimethoprim resistance in Haemophilus influenzae

    NARCIS (Netherlands)

    R. de Groot (Ronald); M. Sluijter (Marcel); A. de Bruyn (Arnoud); J. Campos; W.H.F. Goessens (Wil); A.L. Smith (Arnold); P.W.M. Hermans (Peter)

    1996-01-01

    textabstractWe previously demonstrated that trimethoprim (Tmp) resistance in Haemophilus influenzae is mediated by chromosomally encoded dihydrofolate reductase (DHFR) with a modified primary structure and distinct kinetic properties. To gain insight into the

  10. synthesis and characterization of novel sulfonamides derivatives ...

    African Journals Online (AJOL)

    Newer sulfonamides and their derivatives has obtained great attention in pharmaceutical field in order to compete life threatening issues caused by drug resistant strains of bacteria, i.e. Methicillin resistance as they have unusual ability of acclimatization against stress caused by antibiotics [12]. Disease causing organisms ...

  11. Synthesis and characterization of novel sulfonamides derivatives ...

    African Journals Online (AJOL)

    Five novel sulfonamides derivatives HR5-HR8 and HR14 were synthesized by sulfonylation of primary or secondary amine in the presence of base through nucleophilic substitution reaction. Structural elucidation was carried out through FT-IR, UV, 1H NMR, MS and elemental analysis. Prepared compounds were evaluated ...

  12. A simple urine test for sulfonamides

    Science.gov (United States)

    de Almeida-Filho, Juvenal; de Souza, José Maria

    1983-01-01

    The lack of a simple and reliable test for sulfonamides has created a problem because of the increasing use of these drugs in the chemotherapy of malaria. This paper describes a modification of the Bratton-Marshall technique, for which the reagents are easily obtainable and which can be carried out in simply equipped primary health care laboratories. PMID:6601540

  13. A simple urine test for sulfonamides

    OpenAIRE

    de Almeida-Filho, Juvenal; de Souza, José Maria

    1983-01-01

    The lack of a simple and reliable test for sulfonamides has created a problem because of the increasing use of these drugs in the chemotherapy of malaria. This paper describes a modification of the Bratton-Marshall technique, for which the reagents are easily obtainable and which can be carried out in simply equipped primary health care laboratories.

  14. A versatile dinucleating ligand containing sulfonamide groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

    2014-01-01

    Copper, iron, and gallium coordination chemistries of the new pentadentate bis-sulfonamide ligand 2,6-bis(N-2-pyridylmethylsulfonamido)-4-methylphenol (psmpH3) were investigated. PsmpH3 is capable of varying degrees of deprotonation, and notably, complexes containing the fully trideprotonated...

  15. Secondary Sulfonamides as Effective Lactoperoxidase Inhibitors.

    Science.gov (United States)

    Köksal, Zeynep; Kalin, Ramazan; Camadan, Yasemin; Usanmaz, Hande; Almaz, Züleyha; Gülçin, İlhami; Gokcen, Taner; Gören, Ahmet Ceyhan; Ozdemir, Hasan

    2017-05-24

    Secondary sulfonamides ( 4a - 8h ) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives ( 4a - 8h ) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives ( 4a - 8h ) are effective LPO inhibitors. The K i values of secondary sulfonamide derivatives ( 4a - 8h ) were found in the range of 1.096 × 10 -3 to 1203.83 µM against LPO. However, the most effective inhibition was found for N -(sulfathiazole)-3,4,5-triacetoxybenzamide ( 6a ), with K i values of 1.096 × 10 -3 ± 0.471 × 10 -3 µM as non-competitive inhibition.

  16. Photolysis mechanism of sulfonamide moiety in five-membered sulfonamides: A DFT study.

    Science.gov (United States)

    Ge, Pu; Yu, Hang; Chen, Jingwen; Qu, Jingping; Luo, Yi

    2018-04-01

    Quantum chemical calculations have been performed to investigate the photolysis mechanism of relatively susceptible sulfonamide moiety of five-membered sulfonamide (SA) antibiotics, such as sulfamethoxazole, sulfisoxazole, sulfamethizole, and sulfathiazole. The results show that the ·OH-mediated indirect photolysis of sulfonamide linkage has two possible multi-step reaction pathways, viz., H-abstraction and electrophilic C1-attack, which is contrast to previously reported one-step cleavage manner. The newly proposed indirect photolysis mechanisms could be applied to six-membered SAs such as sulfadimethoxine. It has been found that the dissociation of SN bond is easier in direct photolysis than ·OH-mediated indirect photolysis. Wiberg bond index and LUMO-HOMO energy gap are investigated to clarify the origin of the discrepant reactivity of sulfonamide moiety of SAs at singlet and triplet states. In comparison with singlet states, the SN bond of SAs is weaker at triplet states of SAs and thus results in higher reactivity of sulfonamide moiety, as also suggested by smaller LUMO-HOMO energy gap. This study could add better understanding to the photolysis mechanisms of SAs, which would be also helpful in utilizing quantum chemistry calculation to investigate the behavior and fate of antibiotics in the aquatic environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?

    Science.gov (United States)

    Šmajs, David; Paštěková, Lenka; Grillová, Linda

    2015-10-01

    Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment. © The American Society of Tropical Medicine and Hygiene.

  18. Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?

    Science.gov (United States)

    Šmajs, David; Paštěková, Lenka; Grillová, Linda

    2015-01-01

    Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment. PMID:26217043

  19. Degradation of sulfonamides as a microbial resistance mechanism.

    Science.gov (United States)

    Vila-Costa, Maria; Gioia, Rosalinda; Aceña, Jaume; Pérez, Sandra; Casamayor, Emilio O; Dachs, Jordi

    2017-05-15

    Two of the main mechanisms of bacterial resistance to sulfonamides in aquatic systems, spread of antibiotic resistance genes (ARG) among the microbial community and in-situ bacterial sulfonamide degradation, were studied in mesocosms experiments using water and cobble biofilms from upstream (pristine waters) and downstream (polluted waters) from the Llobregat river, NE Iberian Peninsula. Mesocosms were prepared at two different concentrations (5000 ng/L and 1000 ng/L) of sulfonamides antibiotics (sulfamethazine and sulfamethoxazole). Concentrations of ARG, nutrients, sulfonamides and their degradation products were measured during the time course of the experiments. Sulfonamides were efficiently degraded by the biofilms during the first four weeks of the experiment. The abundance of ARG in biofilms sharply decreased after addition of high concentrations of sulfonamides, but this was not observed in the mesocosms treated with low concentrations of sulfonamides. Sulfonamide degradation was faster in polluted waters and at high concentrations of sulfonamide (and lower ARG abundances), suggesting that both degradation and ARG are two complementary resistance strategies employed by the microbial community. This study shows that microbial degradation of antibiotics is an efficient resistance mechanism coupled with the presence of ARG, and suggests that in situ degradation prevails at high concentrations of antibiotics whereas physiological adaptation by ARG spread would be more important under relatively lower concentrations of antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use.

    Directory of Open Access Journals (Sweden)

    Alma Brolund

    Full Text Available BACKGROUND: Trimethoprim resistance is increasing in Enterobacteriaceae. In 2004-2006 an intervention on trimethoprim use was conducted in Kronoberg County, Sweden, resulting in 85% reduction in trimethoprim prescriptions. We investigated the distribution of dihydrofolate reductase (dfr-genes and integrons in Escherichia coli and Klebsiella pneumoniae and the effect of the intervention on this distribution. METHODOLOGY/PRINCIPAL FINDINGS: Consecutively isolated E. coli (n = 320 and K. pneumoniae (n = 54 isolates phenotypically resistant to trimethoprim were studied. All were investigated for the presence of dfrA1, dfrA5, dfrA7, dfrA8, dfrA12, dfrA14, dfrA17 and integrons class I and II. Isolates negative for the seven dfr-genes (n = 12 were also screened for dfr2d, dfrA3, dfrA9, dfrA10, dfrA24 and dfrA26. These genes accounted for 96% of trimethoprim resistance in E. coli and 69% in K. pneumoniae. The most prevalent was dfrA1 in both species. This was followed by dfrA17 in E. coli which was only found in one K. pneumoniae isolate. Class I and II Integrons were more common in E. coli (85% than in K. pneumoniae (57%. The distribution of dfr-genes did not change during the course of the 2-year intervention. CONCLUSIONS/SIGNIFICANCE: The differences observed between the studied species in terms of dfr-gene and integron prevalence indicated a low rate of dfr-gene transfer between these two species and highlighted the possible role of narrow host range plasmids in the spread of trimethoprim resistance. The stability of dfr-genes, despite large changes in the selective pressure, indirectly suggests a low fitness cost of dfr-gene carriage.

  1. 21 CFR 522.2610 - Trimethoprim and sulfadiazine.

    Science.gov (United States)

    2010-04-01

    ... trimethoprim suspended in a solution containing 400 mg sulfadiazine (as the sodium salt). (b) Sponsors. See Nos... to Streptococcus zooepidemicus. (2) Horses—(i) Amount. 2 mL of the product described in paragraph (a.... Not for use in horses intended for human consumption. [71 FR 30803, May 31, 2006] ...

  2. Effect of trimethoprim-sulfamethoxazole prophylaxis on faecal ...

    African Journals Online (AJOL)

    Effect of trimethoprim-sulfamethoxazole prophylaxis on faecal carriage rates of resistant isolates of Escherichia coli in HIV-infected adult patients in Lagos. ... African Journal of Infectious Diseases ... The Escherichia coli isolates showed a progressive increase in resistance to the tested antibiotics over the 12-month period.

  3. Oral trimethoprim-sulfamethoxazole in the treatment of cerebral ...

    African Journals Online (AJOL)

    Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients - a prospective study. P Francis, V B Patel, P L A Bill, A I Bhigjee. Abstract. Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients, Effective therapy includes pyrimethamine plus ...

  4. Trimethoprim use in early pregnancy and the risk of miscarriage

    DEFF Research Database (Denmark)

    Andersen, J T; Petersen, M; Jimenez-Solem, E

    2013-01-01

    including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox...

  5. Treatment of shigella infections: why sulfamethoxazole-trimethoprim ...

    African Journals Online (AJOL)

    ... and one (1.3%) were Yersinia enterocolitica. Shigella isolates had high resistance to sulfamethoxazole-trimethoprim (97%), tetracycline (83.6%) ampicillin (58.2%) and chloramphenicol (20.9%). The isolates showed low resistance to nalidixic (4.5%) and ciprofloxacin (3.0%) while there was no resistance to ceftriaxone.

  6. Long-term macrolides in diffuse interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Paola Faverio

    2017-12-01

    Full Text Available In the present review we provide currently available evidence for the use of macrolides in the treatment of diffuse interstitial lung diseases (ILDs. Up to now, research on macrolides has mainly focused on three areas. First, macrolides have shown some promising results in cellular models and case reports as antifibrotic agents, by promoting autophagy and clearance of intracellular protein aggregates and acting as regulators of surfactant homeostasis. Secondly, macrolides have an immunomodulatory effect, which has been applied in some organising pneumonia cases. In particular, macrolides have been tested in association with systemic corticosteroids as steroid-sparing agents and alone as either first-line agents in mild cases or second-line agents where steroids were poorly tolerated or had failed. Thirdly, a recent area of research concerns the possible role of macrolides as modulators of lung microbiota and the host–microbiota interaction. This function has been particularly studied in idiopathic pulmonary fibrosis patients, in whom changes in microbiota have been proved to be associated with disease progression. However, the lack of high-quality studies makes the application of macrolide therapy in ILDs a field in which research should be conducted on a large scale.

  7. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human.

    Science.gov (United States)

    Wu, Shuyu; Dalsgaard, Anders; Hammerum, Anette M; Porsbo, Lone J; Jensen, Lars B

    2010-07-30

    Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3) in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids involved in the mobility of sul genes. A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multiplex PCR was conducted to detect the presence of three sul genes among the sulfonamide-resistant E. coli isolates. Fifty-seven sulfonamide-resistant E. coli were selected based on presence of sul resistance genes and subjected to conjugation and/or transformation experiments. S1 nuclease digestion followed by pulsed-field gel electrophoresis was used to visualize and determine the size of plasmids. Plasmids carrying sul genes were characterized by PCR-based replicon typing to allow a comparison of the types of sul genes, the reservoir and plasmid present. A total of 109/501 isolates exhibited sulfonamide resistance. The relative prevalences of sul genes from the three reservoirs (pigs, pig carcasses and humans) were 65%, 45% and 12% for sul2, sul1, and sul3, respectively. Transfer of resistance through conjugation was observed in 42/57 isolates. Resistances to streptomycin, ampicillin and trimethoprim were co-transferred in most strains. Class 1 integrons were present in 80% of sul1-carrying plasmids and 100% of sul3-carrying plasmids, but only in 5% of sul2-carrying plasmids. The sul plasmids ranged from 33 to 160-kb in size and belonged to nine different incompatibility (Inc) groups: FII, FIB, I1, FIA, B/O, FIC, N, HI1 and X1. IncFII was the dominant type in sul2-carrying plasmids (52%), while IncI1 was the most common type in sul1 and sul3-carrying plasmids (33% and 45%, respectively). Multireplicons were found associated with all three sul genes. Sul genes were distributed widely in E. coli isolated

  8. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human

    Directory of Open Access Journals (Sweden)

    Hammerum Anette M

    2010-07-01

    Full Text Available Abstract Background Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3 in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids involved in the mobility of sul genes. Methods A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multiplex PCR was conducted to detect the presence of three sul genes among the sulfonamide-resistant E. coli isolates. Fifty-seven sulfonamide-resistant E. coli were selected based on presence of sul resistance genes and subjected to conjugation and/or transformation experiments. S1 nuclease digestion followed by pulsed-field gel electrophoresis was used to visualize and determine the size of plasmids. Plasmids carrying sul genes were characterized by PCR-based replicon typing to allow a comparison of the types of sul genes, the reservoir and plasmid present. Results A total of 109/501 isolates exhibited sulfonamide resistance. The relative prevalences of sul genes from the three reservoirs (pigs, pig carcasses and humans were 65%, 45% and 12% for sul2, sul1, and sul3, respectively. Transfer of resistance through conjugation was observed in 42/57 isolates. Resistances to streptomycin, ampicillin and trimethoprim were co-transferred in most strains. Class 1 integrons were present in 80% of sul1-carrying plasmids and 100% of sul3-carrying plasmids, but only in 5% of sul2-carrying plasmids. The sul plasmids ranged from 33 to 160-kb in size and belonged to nine different incompatibility (Inc groups: FII, FIB, I1, FIA, B/O, FIC, N, HI1 and X1. IncFII was the dominant type in sul2-carrying plasmids (52%, while IncI1 was the most common type in sul1 and sul3-carrying plasmids (33% and 45%, respectively. Multireplicons were found associated with all three sul genes

  9. Generation of group-specific antibodies against sulfonamides

    NARCIS (Netherlands)

    Cliquet, P.; Cox, E.; Haasnoot, W.; Schacht, E.; Goddeeris, B.M.

    2003-01-01

    To develop a sulfonamide-specific ELISA, different attempts were made to obtain monoclonal antibodies specific for the common structure of sulfonamides. In a first approach, sulfanilamide was linked to albumins using glutaraldehyde or a succinimide ester as cross-linker. A weak immune response or

  10. Gold-catalyzed intermolecular hydroamination of allenes with sulfonamides

    Directory of Open Access Journals (Sweden)

    Chen Zhang

    2013-05-01

    Full Text Available A co-catalyst of (PPh3AuCl/AgOTf for the intermolecular hydroamination of allenes with sulfonamides is shown. The reaction proceeded smoothly under mild conditions for differently substituted allenes giving N-allylic sulfonamides in good yields with high regioselectivity and E-selectivity.

  11. A platform for the discovery of new macrolide antibiotics

    Science.gov (United States)

    Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypiński, Filip T.; Green, William D.; Myers, Andrew G.

    2016-05-01

    The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

  12. Spectrophotometric Investigations of Macrolide Antibiotics: A Brief Review

    Directory of Open Access Journals (Sweden)

    Mrudul R. Keskar

    2015-01-01

    Full Text Available Macrolides, one of the most commonly used class of antibiotics, are a group of drugs produced by Streptomyces species. They belong to the polyketide class of natural products. Their activity is due to the presence of a large macrolide lactone ring with deoxy sugar moieties. They are protein synthesis inhibitors and broad-spectrum antibiotics, active against both gram-positive and gram-negative bacteria. Different analytical techniques have been reported for the determination of macrolides such as chromatographic methods, flow injection methods, spectrofluorometric methods, spectrophotometric methods, and capillary electrophoresis methods. Among these methods, spectrophotometric methods are sensitive and cost effective for the analysis of various antibiotics in pharmaceutical formulations as well as biological samples. This article reviews different spectrophotometric methods for the determination of macrolide antibiotics.

  13. Use of macrolides in lung diseases: recent literature controversies

    Directory of Open Access Journals (Sweden)

    Luiz Vicente Ribeiro Ferreira da Silva Filho

    2015-11-01

    Conclusions: The long‐term use of macrolides should be limited to highly selected situations, especially in patients with bronchiectasis. Careful evaluation of the benefits and potential damage are tools for their indication in specific groups.

  14. Transport of sulfonamide antibiotics in crop fields during monsoon season.

    Science.gov (United States)

    Park, Jong Yol; Ruidisch, Marianne; Huwe, Bernd

    2016-11-01

    Previous studies have documented the occurrence of veterinary sulfonamide antibiotics in groundwater and rivers located far from pollution sources, although their transport and fate is relatively unknown. In mountainous agricultural fields, the transport behaviour can be influenced by climate, slope and physico-chemical properties of the sulfonamides. The objective of this research is to describe the transport behaviour of three sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) in sloped agricultural fields located in the Haean catchment, South Korea. During dry and monsoon seasons, a solute transport experiment was conducted in two typical sandy loam agricultural fields after application of antibiotics and potassium bromide as conservative tracers. Field measurement and modelling revealed that frequency and amount of runoff generation indicate a relation between slope and rain intensity during monsoon season. Since the steepness of slope influenced partitioning of precipitation between runoff and subsurface flow, higher loss of sulfonamide antibiotics and bromide by runoff was observed at the steeper sloped field. Bromide on topsoil rapidly infiltrated at high infiltration rates. On the contrary, the sulfonamides were relatively retarded in the upper soil layer due to adsorption onto soil particles. Presence of furrows and ridges affected the distribution of sulfonamide antibiotics in the subsurface due to gradient from wetter furrows to drier ridges induced by topography. Modelling results with HydroGeoSphere matched with background studies that describe physico-chemical properties of the sulfonamides interaction between soil and the antibiotic group, solute transport through vadose zone and runoff generation by storm events.

  15. Effect of humic acid (HA) on sulfonamide sorption by biochars

    International Nuclear Information System (INIS)

    Lian, Fei; Sun, Binbin; Chen, Xi; Zhu, Lingyan; Liu, Zhongqi; Xing, Baoshan

    2015-01-01

    Effect of quantity and fractionation of loaded humic acid (HA) on biochar sorption for sulfonamides was investigated. The HA was applied in two different modes, i.e. pre-coating and co-introduction with sorbate. In pre-coating mode, the polar fractions of HA tended to interact with low-temperature biochars via H-bonding, while the hydrophobic fractions were likely to be adsorbed by high-temperature biochars through hydrophobic and π-π interactions, leading to different composition and structure of the HA adlayers. The influences of HA fractionation on biochar sorption for sulfonamides varied significantly, depending on the nature of interaction between HA fraction and sorbate. Meanwhile, co-introduction of HA with sulfonamides revealed that the effect of HA on sulfonamide sorption was also dependent on HA concentration. These findings suggest that the amount and fractionation of adsorbed HA are tailored by the surface properties of underlying biochars, which differently affect the sorption for organic contaminants. - Highlights: • Effect of quantity and fractionation of coated HA on sorption of sulfonamides by BC was studied. • Fractionation of coated HA is tailored by surface properties of BC. • Roles of HA in BC sorption depend on interaction between HA adlayer and sorbate. • Roles of HA in sulfonamide sorption by BC also depend on HA aqueous concentration. - The quantity and fractionation of adsorbed HA play a major role in sulfonamide sorption by biochars

  16. Palladium-catalysed arylation of sulfonamide stabilised enolates

    CSIR Research Space (South Africa)

    Zeevaart, JG

    2005-03-07

    Full Text Available of an arylation reaction is found where the nucleophile is a sulfonamide.8 However, the success of this procedure required an enhancement of the acidity of the subject sulfonamide through the gener- ation of a b-cyanosulfonamide. The relatively acidic 2-[N... liquid ammonia chemistry.9 The preparation of compounds such as 1, containing both a sulfonamide and a cyano substituent to enhance the acidity of the protons between both functional groups, is relatively cumbersome. In cases where the a- aryl...

  17. Sequence-Dependent Elongation Dynamics on Macrolide-Bound Ribosomes

    Directory of Open Access Journals (Sweden)

    Magnus Johansson

    2014-06-01

    Full Text Available The traditional view of macrolide antibiotics as plugs inside the ribosomal nascent peptide exit tunnel (NPET has lately been challenged in favor of a more complex, heterogeneous mechanism, where drug-peptide interactions determine the fate of a translating ribosome. To investigate these highly dynamic processes, we applied single-molecule tracking of elongating ribosomes during inhibition of elongation by erythromycin of several nascent chains, including ErmCL and H-NS, which were shown to be, respectively, sensitive and resistant to erythromycin. Peptide sequence-specific changes were observed in translation elongation dynamics in the presence of a macrolide-obstructed NPET. Elongation rates were not severely inhibited in general by the presence of the drug; instead, stalls or pauses were observed as abrupt events. The dynamic pathways of nascent-chain-dependent elongation pausing in the presence of macrolides determine the fate of the translating ribosome stalling or readthrough.

  18. Macrolide overuse for treatment of respiratory tract infections in general practice

    DEFF Research Database (Denmark)

    Hinnerskov, Mette; Therkildsen, Julie Maria; Cordoba, Gloria

    2011-01-01

    High consumption of macrolides has been linked to increased macrolide resistance in the common pathogens of respiratory tract infections (RTIs). According to Danish recommendations, penicillin is the first-choice treatment for RTIs and macrolides should only be prescribed when a patient is allergic...... to penicillin or for treatment of mycoplasma pneumonias. The aim of the present study was to explore the prescription of macrolides for different RTIs to patients without penicillin allergy in general practice in Denmark....

  19. Impaired Fitness and Transmission of Macrolide-Resistant Campylobacter jejuni in Its Natural Host

    OpenAIRE

    Luangtongkum, Taradon; Shen, Zhangqi; Seng, Virginia W.; Sahin, Orhan; Jeon, Byeonghwa; Liu, Peng; Zhang, Qijing

    2012-01-01

    Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter has become a concern for public health. To facilitate the control of macrolide-resistant Campylobacter, it is necessary to understand if macrolide resistance affects the fitness...

  20. FMNH2-dependent monooxygenases initiate catabolism of sulfonamides in Microbacterium sp. strain BR1 subsisting on sulfonamide antibiotics.

    Science.gov (United States)

    Ricken, Benjamin; Kolvenbach, Boris A; Bergesch, Christian; Benndorf, Dirk; Kroll, Kevin; Strnad, Hynek; Vlček, Čestmír; Adaixo, Ricardo; Hammes, Frederik; Shahgaldian, Patrick; Schäffer, Andreas; Kohler, Hans-Peter E; Corvini, Philippe F-X

    2017-11-17

    We report a cluster of genes encoding two monooxygenases (SadA and SadB) and one FMN reductase (SadC) that enable Microbacterium sp. strain BR1 and other Actinomycetes to inactivate sulfonamide antibiotics. Our results show that SadA and SadC are responsible for the initial attack of sulfonamide molecules resulting in the release of 4-aminophenol. The latter is further transformed into 1,2,4-trihydroxybenzene by SadB and SadC prior to mineralization and concomitant production of biomass. As the degradation products lack antibiotic activity, the presence of SadA will result in an alleviated bacteriostatic effect of sulfonamides. In addition to the relief from antibiotic stress this bacterium gains access to an additional carbon source when this gene cluster is expressed. As degradation of sulfonamides was also observed when Microbacterium sp. strain BR1 was grown on artificial urine medium, colonization with such strains may impede common sulfonamide treatment during co-infections with pathogens of the urinary tract. This case of biodegradation exemplifies the evolving catabolic capacity of bacteria, given that sulfonamide bacteriostatic are purely of synthetic origin. The wide distribution of this cluster in Actinomycetes and the presence of traA encoding a relaxase in its vicinity suggest that this cluster is mobile and that is rather alarming.

  1. A novel regiospecific cascade synthesis of sulfonamide derivatives from N-(2-polychloroethyl)sulfonamides via chloroaziridine intermediates in the presence of mercaptoethanol.

    Science.gov (United States)

    Rozentsveig, Igor B; Popov, Aleksandr V; Rozentsveig, Gulnur N; Serykh, Valeriy Yu; Chernyshev, Kirill A; Krivdin, Leonid B; Levkovskaya, Galina G

    2010-08-01

    N-(1-Aryl-2-polychloroethyl)arenesulfonamides obtained on the basis of N,N-dichlorosulfoamides and polychloroethenes or phenylacetylene undergo a reaction cascade in the presence of mercaptoethanol. The reaction cascade opens a new route to the series of cyclic or open-chain sulfonamide derivatives. The process includes cyclization to aziridine intermediates, their further recyclization, and isomerization to imidoylchlorides or chloroimines, followed by substitution or reduction under the action of mercaptoethanol or hydrolysis. The final sulfonamide structures depend on the starting N-(polychloroethyl)sulfonamides. N-(2,2-Dichloroethyl)sulfonamides were transformed into sulfonamide-containing 1,4-oxathians while N-(2,2,2-trichloroethyl)sulfonamides were converted to N-(2-arylacetyl)arenesulfonamides. N-(2-Phenyl-2,2-dichloroethyl)sulfonamides form enamide derivatives that were transformed into aromatic ketones.

  2. Radiosterilization of sulfonamides: I: determination of the effects of gamma irradiation on solid sulfonamides

    International Nuclear Information System (INIS)

    Mercanoglu, G.O.; Oezer, A.Y.; Colak, S.S.; Korkmaz, M.; Oezalp, M.; Ekizoglu, M.; Barbarin, N.; Tilquin, B.

    2004-01-01

    Three antibiotics sulfafurazole (SFZ), sulfamethoxazole (SMZ) and sulfacetamide sodium (SSA-Na) belonging to sulfonamides were irradiated and changes in physico-chemical properties, pH, melting points, UV, IR, NMR, TLC, GC-MS, ESR characteristics, antimicrobial activities of active components were studied at normal and accelerated stability test conditions. Two radiolytic intermediates for both SFZ and SMZ and four radiolytic intermediates for SSA-Na were found in the irradiated solid samples after the GC-MS analysis. The results obtained under normal and accelerated stability test conditions were observed to be consistent with the unirradiated values

  3. Radiosterilization of sulfonamides: I: determination of the effects of gamma irradiation on solid sulfonamides

    Energy Technology Data Exchange (ETDEWEB)

    Mercanoglu, G.O.; Oezer, A.Y. E-mail: ayozer@yahoo.com; Colak, S.S.; Korkmaz, M.; Oezalp, M.; Ekizoglu, M.; Barbarin, N.; Tilquin, B

    2004-04-01

    Three antibiotics sulfafurazole (SFZ), sulfamethoxazole (SMZ) and sulfacetamide sodium (SSA-Na) belonging to sulfonamides were irradiated and changes in physico-chemical properties, pH, melting points, UV, IR, NMR, TLC, GC-MS, ESR characteristics, antimicrobial activities of active components were studied at normal and accelerated stability test conditions. Two radiolytic intermediates for both SFZ and SMZ and four radiolytic intermediates for SSA-Na were found in the irradiated solid samples after the GC-MS analysis. The results obtained under normal and accelerated stability test conditions were observed to be consistent with the unirradiated values.

  4. [Pharmacokinetics of hypoglycemic sulfonamides: Ozidia, a new concept].

    Science.gov (United States)

    Selam, J L

    1997-11-01

    Hypoglycaemic sulfonamides differ in their properties, which vary in clinical importance. The potency of sulfonamide has increased with the generations. However, this potency is compensated in practice by the dose prescribed, which is much smaller for recent generations. The half-life is a far more important property. The effective action period is correlated with half-life but is much longer. The action period for "short-term" sulfonamides is fasting hepatic glucose production, which is particularly increased early in the day in non-insulin-dependent diabetic patients because of a circadian drop in insulin sensitivity (dawn phenomenon). Finally, in chronic administration, all sulfonamides cause a progressive desensitisation of the beta cell, which responds by an insulin secretion peak only during food intake. This condition indicates the unuselessness of sulfonamide fractionation and, contrary to the classic notion, the low risk of hypoglycaemia after a meal is skipped. The ideal product would be a sulfonamide with high potency and an ultra-short half-life, but capable of maintaining plasma concentrations for 24 h (which might seem incompatible except in continuous administration). Moreover, it would exert its action at relatively low levels of insulinaemia and be completely metabolisable. Glipizide in its osmotic oral form (Ozidia) satisfies all these conditions since it is a very potent sulfonamide with a quite short half-life but with intestinal delivery up to 16 h after administration because of its osmotic principle. It controls fasting glycaema better than ordinary glipizide and at least as well as glibenclamide by acting on hepatic glucose production. Compared to glibenclamide, it has the advantage of generation this effect at lower levels of insulinaemia. In comparison with normal glipizide, it allows identical control for lower postprandial inslinaemias, which is proof of its powerful inductive effect on insulin sensitivity.

  5. Toward the rational design of macrolide antibiotics to combat resistance.

    Science.gov (United States)

    Pavlova, Anna; Parks, Jerry M; Oyelere, Adegboyega K; Gumbart, James C

    2017-11-01

    Macrolides, one of the most prescribed classes of antibiotics, bind in the bacterial ribosome's polypeptide exit tunnel and inhibit translation. However, mutations and other ribosomal modifications, especially to the base A2058 of the 23S rRNA, have led to a growing resistance problem. Here, we have used molecular dynamics simulations to study the macrolides erythromycin and azithromycin in wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli ribosomes. We find that the ribosomal modifications result in less favorable interactions between the base 2058 and the desosamine sugar of the macrolides, as well as greater displacement of the macrolides from their crystal structure position, illuminating the causes of resistance. We have also examined four azithromycin derivatives containing aromatic indole-analog moieties, which were previously designed based on simulations of the stalling peptide SecM in the ribosome. Surprisingly, we found that the studied moieties could adopt very different geometries when interacting with a key base in the tunnel, A751, possibly explaining their distinct activities. Based on our simulations, we propose modifications to the indole-analog moieties that should increase their interactions with A751 and, consequently, enhance the potency of future azithromycin derivatives. © 2017 John Wiley & Sons A/S.

  6. Biosynthesis and pathway engineering of antifungal polyene macrolides in actinomycetes.

    Science.gov (United States)

    Kong, Dekun; Lee, Mi-Jin; Lin, Shuangjun; Kim, Eung-Soo

    2013-06-01

    Polyene macrolides are a large family of natural products typically produced by soil actinomycetes. Polyene macrolides are usually biosynthesized by modular and large type I polyketide synthases (PKSs), followed by several steps of sequential post-PKS modifications such as region-specific oxidations and glycosylations. Although known as powerful antibiotics containing potent antifungal activities (along with additional activities against parasites, enveloped viruses and prion diseases), their high toxicity toward mammalian cells and poor distribution in tissues have led to the continuous identification and structural modification of polyene macrolides to expand their general uses. Advances in in-depth investigations of the biosynthetic mechanism of polyene macrolides and the genetic manipulations of the polyene biosynthetic pathways provide great opportunities to generate new analogues. Recently, a novel class of polyene antibiotics was discovered (a disaccharide-containing NPP) that displays better pharmacological properties such as improved water-solubility and reduced hemolysis. In this review, we summarize the recent advances in the biosynthesis, pathway engineering, and regulation of polyene antibiotics in actinomycetes.

  7. Interstitial lung disease during trimethoprim/sulfamethoxazole administration

    International Nuclear Information System (INIS)

    Yuzurio, Syota; Horita, Naokatsu; Shiota, Yutaro; Kanehiro, Arihiko; Tanimoto, Mitsune

    2010-01-01

    We studied clinical and radiographic features of interstitial lung disease (ILD) during trimethoprim/sulfamethoxazole (TMP/SMX) administration. Ten patients who had received prednisolone treatment for underlying diffuse pulmonary disease showed various ILDs after introduction of TMP/SMX. The radiographic features of the ILDs were not consistent with infectious disease or exacerbation of the underlying disease, and these diagnoses were excluded radiographically and on clinical grounds during the differential diagnosis of the ILDs. These ILDs emerged relatively early after introduction of TMP/SMX, which is consistent with the former case report of drug-induced ILD (DI-ILD) caused by TMP/SMX. Therefore DI-ILDs caused by TMP/SMX were suspected in these cases. In most of these cases, the ILDs were clinically mild and disappeared immediately although administration of TMP/SMX was continued. (author)

  8. TREATMENT OF IMPETIGO WITH SULFONAMIDE-UREA POWDER

    Science.gov (United States)

    Rees, Rees B.; Hamlin, Edwin M.; McGinley, James P.

    1952-01-01

    Sulfonamides can be used in the treatment of impetigo with vastly increased safety and with more effectiveness in powder rather than ointment form when combined with urea powder in a ratio of approximately three parts of sulfonamide to one of urea. Of 701 patients treated with such a mixture, 95.6 per cent were cured within a week. The only complication was local dermatitis which occurred in 0.57 per cent of patients. This compares favorably with results obtained with newer and expensive drugs which usually have the disadvantage of being used in a greasy vehicle. The low incidence of sensitivity reaction to the sulfonamide-urea powder is perhaps ascribable in part to the avoidance of a greasy vehicle. PMID:14935883

  9. Comparative mobility of sulfonamides and bromide tracer in three soils

    Science.gov (United States)

    Kurwadkar, S.T.; Adams, C.D.; Meyer, M.T.; Kolpin, D.W.

    2011-01-01

    In animal agriculture, sulfonamides are one of the routinely used groups of antimicrobials for therapeutic and sub-therapeutic purposes. It is observed that, the animals when administered the antimicrobials, often do not completely metabolize them; and excrete the partially metabolized forms into the environment. Due to the continued use of antimicrobials and disposal of untreated waste, widespread occurrence of partially metabolized antimicrobials in aquatic and terrestrial environments has been reported in various scientific journals. In this research, the mobility of two sulfonamides - sulfamethazine (SMN), sulfathiazole (STZ) and a conservative bromide tracer was investigated in three soils collected from regions in the United States with large number of concentrated animal-feed operations. Results of a series of column studies indicate that the mobility of these two sulfonamides was dependent on pH, soil charge density, and contact time. At low pH and high charge density, substantial retention of sulfonamides was observed in all three soils investigated, due to the increased fraction of cationic and neutral forms of the sulfonamides. Conversely, enhanced mobility was observed at high pH, where the sulfonamides are predominantly in the anionic form. The results indicate that when both SMN and STZ are predominantly in anionic forms, their mobility approximates the mobility of a conservative bromide tracer. This observation is consistent for the mobility of both SMN and STZ individually, and also in the presence of several other antimicrobials in all three soils investigated. Higher contact time indicates lower mobility due to increased interaction with soil material. ?? 2011.

  10. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Zuercher, William J.; Buckholz†, Richard G.; Campobasso, Nino; Collins, Jon L.; Galardi, Cristin M.; Gampe, Robert T.; Hyatt, Stephen M.; Merrihew, Susan L.; Moore, John T.; Oplinger, Jeffrey A.; Reid, Paul R.; Spearing, Paul K.; Stanley, Thomas B.; Stewart, Eugene L.; Willson, Timothy M. (GSKNC)

    2010-08-12

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  11. Within-Population Distribution of Trimethoprim Resistance in Escherichia coli before and after a Community-Wide Intervention on Trimethoprim Use

    Science.gov (United States)

    Sundqvist, Martin; Granholm, Susanne; Naseer, Umaer; Rydén, Patrik; Brolund, Alma; Sundsfjord, Arnfinn; Kahlmeter, Gunnar

    2014-01-01

    A 2-year prospective intervention on the prescription of trimethoprim reduced the use by 85% in a health care region with 178,000 inhabitants. Here, we performed before-and-after analyses of the within-population distribution of trimethoprim resistance in Escherichia coli. Phylogenetic and population genetic methods were applied to multilocus sequence typing data of 548 consecutively collected E. coli isolates from clinical urinary specimens. Results were analyzed in relation to antibiotic susceptibility and the presence and genomic location of different trimethoprim resistance gene classes. A total of 163 E. coli sequence types (STs) were identified, of which 68 were previously undescribed. The isolates fell into one of three distinct genetic clusters designated BAPS 1 (E. coli phylogroup B2), BAPS 2 (phylogroup A and B1), and BAPS 3 (phylogroup D), each with a similar frequency before and after the intervention. BAPS 2 and BAPS 3 were positively and BAPS 1 was negatively associated with trimethoprim resistance (odds ratios of 1.97, 3.17, and 0.26, respectively). In before-and-after analyses, trimethoprim resistance frequency increased in BAPS 1 and decreased in BAPS 2. Resistance to antibiotics other than trimethoprim increased in BAPS 2. Analysis of the genomic location of different trimethoprim resistance genes in isolates of ST69, ST58, and ST73 identified multiple independent acquisition events in isolates of the same ST. The results show that despite a stable overall resistance frequency in E. coli before and after the intervention, marked within-population changes occurred. A decrease of resistance in one major genetic cluster was masked by a reciprocal increase in another major cluster. PMID:25288078

  12. Macrolide antibiotics allosterically predispose the ribosome for translation arrest.

    Science.gov (United States)

    Sothiselvam, Shanmugapriya; Liu, Bo; Han, Wei; Ramu, Haripriya; Klepacki, Dorota; Atkinson, Gemma Catherine; Brauer, Age; Remm, Maido; Tenson, Tanel; Schulten, Klaus; Vázquez-Laslop, Nora; Mankin, Alexander S

    2014-07-08

    Translation arrest directed by nascent peptides and small cofactors controls expression of important bacterial and eukaryotic genes, including antibiotic resistance genes, activated by binding of macrolide drugs to the ribosome. Previous studies suggested that specific interactions between the nascent peptide and the antibiotic in the ribosomal exit tunnel play a central role in triggering ribosome stalling. However, here we show that macrolides arrest translation of the truncated ErmDL regulatory peptide when the nascent chain is only three amino acids and therefore is too short to be juxtaposed with the antibiotic. Biochemical probing and molecular dynamics simulations of erythromycin-bound ribosomes showed that the antibiotic in the tunnel allosterically alters the properties of the catalytic center, thereby predisposing the ribosome for halting translation of specific sequences. Our findings offer a new view on the role of small cofactors in the mechanism of translation arrest and reveal an allosteric link between the tunnel and the catalytic center of the ribosome.

  13. Detection of macrolide resistance in Mycoplasma genitalium in France.

    Science.gov (United States)

    Chrisment, Delphine; Charron, Alain; Cazanave, Charles; Pereyre, Sabine; Bébéar, Cécile

    2012-11-01

    Mycoplasma genitalium is a sexually transmitted organism associated with non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women. Resistance to macrolides has been recently associated with point mutations in the 23S rRNA gene. The aim of this study was to detect these mutations using a large French collection of M. genitalium-positive specimens. We evaluated whether these mutations were related to azithromycin treatment failure and whether macrolide-resistant M. genitalium may be spreading. A retrospective study conducted in France between 2003 and 2010 included 156 urogenital clinical specimens from 136 patients that were positive for M. genitalium. Mutations in domain V of M. genitalium 23S rRNA were detected using amplification and sequencing. The mutated strains were genotyped by studying single nucleotide polymorphisms in the mgpB gene. We have detected macrolide resistance-associated mutations in M. genitalium since 2006 at a rate of 13.2%, ranging from 10% to 15.4% of patients per year. Nine mutations at position 2059 as well as two A2058G substitutions, one A2062T substitution and one C2038T substitution (Escherichia coli numbering) were identified in M. genitalium. These patients had treatment failure with azithromycin in 75% (6/8) of cases. For one patient, genotyping showed selection for the mutation during treatment with azithromycin. For the first time, we describe macrolide resistance for M. genitalium in France and demonstrate that its detection has increased since 2006. Epidemiological surveillance of M. genitalium is necessary to adapt treatments to M. genitalium infections.

  14. Voltammetric investigation of macrolides by an HPLC-coulometric assay.

    Science.gov (United States)

    Kim, Yong-Hak; Pothuluri, Jairaj V; Cerniglia, Carl E

    2005-07-01

    Voltammograms of macrolides, including anhydroerythromycin A, azithromycin, erythromycin A, erythromycin A enol ether, pseudoerythromycin A enol ether, oleandomycin and tylosin have been investigated using a dual electrode cell in combination with a high-throughput LC method. The half-wave potentials (E(1/2)) of the seven macrolides investigated ranged from 0.734 to 0.866 V, and the current responses reached the maxima at over 1.0 V. The current response of the downstream electrode displayed a non-linear behavior at high potentials over +0.75 V, probably because of polarization of solvent components, e.g., water. The HPLC-coulometric assay was optimized with the potentials of the upstream and downstream electrodes at +0.65 and +0.85 V, respectively. This method is suitable for detection of 14- and 15-membered macrolides (sensitivitytylosin (sensitivity>0.1 microg ml(-1)). The assay shows interferences from biomatrices in rat's blood plasma and serum, and human urine, but they were effectively removed by a cold acetonitrile extraction method.

  15. Sequence-dependent elongation dynamics on macrolide-bound ribosomes.

    Science.gov (United States)

    Johansson, Magnus; Chen, Jin; Tsai, Albert; Kornberg, Guy; Puglisi, Joseph D

    2014-06-12

    The traditional view of macrolide antibiotics as plugs inside the ribosomal nascent peptide exit tunnel (NPET) has lately been challenged in favor of a more complex, heterogeneous mechanism, where drug-peptide interactions determine the fate of a translating ribosome. To investigate these highly dynamic processes, we applied single-molecule tracking of elongating ribosomes during inhibition of elongation by erythromycin of several nascent chains, including ErmCL and H-NS, which were shown to be, respectively, sensitive and resistant to erythromycin. Peptide sequence-specific changes were observed in translation elongation dynamics in the presence of a macrolide-obstructed NPET. Elongation rates were not severely inhibited in general by the presence of the drug; instead, stalls or pauses were observed as abrupt events. The dynamic pathways of nascent-chain-dependent elongation pausing in the presence of macrolides determine the fate of the translating ribosome stalling or readthrough. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Distribution of sulfamonomethoxine and trimethoprim in egg yolk and white.

    Science.gov (United States)

    Bilandžić, Nina; Božić, Đurđica; Kolanović, Božica Solomun; Varenina, Ivana; Cvetnić, Luka; Cvetnić, Željko

    2015-07-01

    The distribution of sulfamonomethoxine (SMM) and trimethoprim (TMP) in egg yolk and white was measured during and after administration of a SMM/TMP combination in laying hens in doses of 8 g l(-)(1) and 12 g l(-)(1) in drinking water for 7 days. The SMM concentration reached maximal levels on day 2 of the post-treatment period for both doses (μg kg(-)(1)): 5920 and 9453 in yolk; 4831 and 6050 in white, in doses 1 and 2, respectively. Significant differences in the SMM and TMP concentrations between yolk and white in post treatment period were found. SMM dropped below the LOD (1.9 μg kg(-1)) in yolk after day 16 and 19 for doses 1 and 2. TMP reached maximal levels on day 3 after drug administration for doses 1 and 2 (μg kg(-)(1)): 6521 and 7329 in yolk, 1370 and 1539 in white. TMP residues were measured above LOD (0.3 μg kg(-)(1)) in yolk for both doses on day 37 post-treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Possible Trimethoprim-Sulfamethoxazole-Induced Hemolytic Anemia: A Case Report.

    Science.gov (United States)

    Williams, Montgomery F; Doss, Emily P; Montgomery, Maggie

    2017-12-01

    To report a case of hemolytic anemia in a patient who received trimethoprim/sulfamethoxazole (TMP-SMX) for a urinary tract infection (UTI). A 47-year-old woman recently diagnosed with uncomplicated UTI received 3 doses of TMP-SMX. She developed yellowing of the skin and eyes, lethargy, mild abdominal pain, and dry mucous membranes. Laboratory testing demonstrated significant anemia with red blood cells (RBCs) of 1.99, hemoglobin (Hgb) of 6.3 g/dL, and hematocrit (Hct) of 18.1%. TMP-SMX was immediately discontinued. The patient was given methylprednisolone 60 mg intravenously (IV) followed by oral steroids and infused with 3 units of packed RBCs over the course of a 10-day inpatient admission. On discharge, the patient continued oral steroids. Outpatient follow-up indicated Hgb of 11.0 g/dL and Hct of 32.7%, 41 days after hospital discharge. Utilizing the Naranjo adverse drug reaction probability scale, there is a probable association between the patient's hemolytic anemia and TMP-SMX. We report a case of hemolytic anemia resulting from the use of TMP-SMX. Although this is a rare adverse effect, clinicians should be aware of the signs and symptoms of hemolytic anemia, and so appropriate treatment can be administered should it occur.

  18. Synthesis and antibacterial activity of sulfonamide derivatives at C-8 ...

    Indian Academy of Sciences (India)

    Synthesis and antibacterial activity of some novel biologically active sulfonamide derivatives at C-8 alkyl chain of anacardic acid (7a-7l), prepared from commercially available anacardic acid mixture (1a-d). These compounds were tested for Gram positive and Gram negative bacterial cultures; most of the compounds ...

  19. Selective degradation of splicing factor CAPERα by anticancer sulfonamides.

    Science.gov (United States)

    Uehara, Taisuke; Minoshima, Yukinori; Sagane, Koji; Sugi, Naoko Hata; Mitsuhashi, Kaoru Ogawa; Yamamoto, Noboru; Kamiyama, Hiroshi; Takahashi, Kentaro; Kotake, Yoshihiko; Uesugi, Mai; Yokoi, Akira; Inoue, Atsushi; Yoshida, Taku; Mabuchi, Miyuki; Tanaka, Akito; Owa, Takashi

    2017-06-01

    Target-protein degradation is an emerging field in drug discovery and development. In particular, the substrate-receptor proteins of the cullin-ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory drugs (IMiDs), such as lenalidomide. Here, we demonstrate that a series of anticancer sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing factor coactivator of activating protein-1 and estrogen receptors (CAPERα) via CRL4 DCAF15 mediated ubiquitination in human cancer cell lines. Both CRISPR-Cas9-based knockout of DCAF15 and a single amino acid substitution of CAPERα conferred resistance against sulfonamide-induced CAPERα degradation and cell-growth inhibition. Thus, these sulfonamides represent selective chemical probes for disrupting CAPERα function and designate DCAFs as promising drug targets for promoting selective protein degradation in cancer therapy.

  20. Trimethoprim Use prior to Pregnancy and the Risk of Congenital Malformation

    DEFF Research Database (Denmark)

    Andersen, Jon Trærup; Petersen, Morten; Jimenez-Solem, Espen

    2013-01-01

    Objectives. The aim of the study was to investigate whether the use of the antifolate antibiotic trimethoprim during the 12 weeks before conception was associated with congenital malformations. Methods. We conducted a nationwide register-based cohort study including all Danish women giving birth...... from 1997 to 2004. All women with at least one prescription of trimethoprim dispensed during the 12 weeks before conception were identified. Results. There was a doubling of congenital malformations in offspring to women exposed to trimethoprim in the 12 weeks before conception. The adjusted odds ratio...... (OR) of major congenital malformation was 1.87, 95% confidence interval (CI) 1.25-2.81. There was a significant increase in major malformations of the heart (OR = 2.49; 1.18-5.26) and limbs (OR = 2.18; 1.13-4.23). Conclusions. In this study, we found an association between exposure to trimethoprim...

  1. Epigallocatechin gallate as a modulator of Campylobacter resistance to macrolide antibiotics.

    Science.gov (United States)

    Kurinčič, Marija; Klančnik, Anja; Smole Možina, Sonja

    2012-11-01

    Comprehensive therapeutic use of macrolides in humans and animals is important in the selection of macrolide-resistant Campylobacter isolates. This study shows high co-resistance to erythromycin, azithromycin, clarithromycin, dirithromycin and tylosin, with contributions from the 23S rRNA gene and drug efflux systems. The CmeABC efflux pump plays an important role in reduced macrolide susceptibility, accompanied by contributions from the CmeDEF efflux pump and potentially a third efflux pump. To improve clinical performance of licensed antibiotics and chemotherapeutic agents, it is important to understand the factors in Campylobacter that affect susceptibility to macrolide antibiotics. Using mutants that lack the functional genes coding for the CmeB and CmeF efflux pump proteins and the CmeR transcriptional repressor, we show that these efflux pumps are potential targets for the development of therapeutic strategies that use a combination of a macrolide with an efflux pump inhibitor (EPI) to restore macrolide efficacy. The natural phenolic compound epigallocatechin gallate (EGCG) has good modulatory activity over the extrusion across the outer membrane of the macrolides tested, both in sensitive and resistant Campylobacter isolates. Comparing EGCG with known chemical EPIs, correlations in the effects on the particular macrolide antibiotics were seen. EGCG modifies Campylobacter multidrug efflux systems and thus could have an impact on restoring macrolide efficacy in resistant strains. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Acyloxymethyl as a drug protecting group. Part 6: N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides as prodrugs of agents containing a secondary sulfonamide group.

    Science.gov (United States)

    Lopes, F; Moreira, R; Iley, J

    2000-04-01

    Tertiary N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides were synthesised and evaluated as novel classes of potential prodrugs of agents containing a secondary sulfonamide group. The chemical and plasma hydrolyses of the title compounds were studied by HPLC. Tertiary N-acyloxymethylsulfonamides are slowly and quantitatively hydrolysed to the parent sulfonamide in pH 7.4 phosphate buffer, with half-lives ranging from 20 h, for 7d, to 30 days, for 7g. Quantitative formation of the parent sulfonamide also occurs in human plasma, the half-lives being within 0.2-2.0 min for some substrates. The rapid rate of hydrolysis can be ascribed to plasma cholinesterase, as indicated by the complete inhibition observed at [eserine] = 0.10 mM. These results suggest that tertiary N-acyloxymethylsulfonamides are potentially useful prodrugs for agents containing a secondary sulfonamide group, especially with pKa sulfonamides 7h-j do not liberate the parent sulfonamide either in aqueous buffers or in human plasma and thus appear to be unsuitable for development as sulfonamide prodrugs.

  3. Trimethoprim/sulfamethoxazole-induced acute renal failure: A case report

    Directory of Open Access Journals (Sweden)

    Gabriella Nucera

    2017-07-01

    Full Text Available The patient was an 80-year-old man who arrived at the emergency room with breathing problems. He presented a history of chronic obstructive pulmonary disease (COPD, hypertension, diabetes mellitus and early (stage 1 chronic renal failure with normal levels of creatinine and no sign and symptoms of renal disease. A chest X-ray showed pneumonia. Therefore, he was first treated with 1 g daily of ceftriaxone IV. We did not observe any clinical improvement, and for this reason, a sputum culture was performed to guide the right antibiotic treatment. Subsequently, we started a new antibiotic therapy with trimethoprim/sulfamethoxazole (TMP/SMX adjusted to renal functioning. Appropriate medical treatment was administered, as well as urine alkalinisation. After the first day of treatment, the patient’s clinical and laboratory status worsened very quickly, with an increased level of serum creatinine from 1.5 to 3.5 mg/dL. We stopped administering the antibiotic therapy immediately. However, we observed acute renal failure with a serum creatinine level of 9.0 mg/dL and four days after his admission, the patient died. Literature showed that patients can develop acute kidney injury (AKI during or immediately following TMP/SMX therapy. Intrinsic renal impairment –rather, interstitial nephritis– appeared responsible for the great majority of cases, and impairment was transient if therapy was discontinued. In our study, despite the therapy with TMP/SMX was immediately discontinued, and our patient underwent appropriate medical treatment, urine alkalinisation and, then, haemodialysis, the AKI was rapidly fatal. In conclusion, particular attention should be paid to prescribing TMP/SMX to patients affected by chronic renal failure.

  4. Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

    Science.gov (United States)

    2006-11-01

    that other antibiotics, such as amoxicillin, cefaclor, penicillin, and cephalosporin , had no such effects even at high concentration (data not...amino sugars attached. Macrolides: broad spectrum antibiotics. Macrolides Have Anti-Inflammatory Activities Roxithromycin: a representative macrolide

  5. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections.

    Science.gov (United States)

    Miller, Loren G; Daum, Robert S; Creech, C Buddy; Young, David; Downing, Michele D; Eells, Samantha J; Pettibone, Stephanie; Hoagland, Rebecca J; Chambers, Henry F

    2015-03-19

    Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear. We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment. A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups. We found no significant difference between clindamycin and TMP-SMX, with respect to either

  6. Anti-microbial activities of sulfonamides using disc diffusion method.

    Science.gov (United States)

    Ahmad, Saba; Farrukh, Muhammad Akhyar

    2012-10-01

    Sulfonamides, being the member of the oldest anti-microbial group of compounds possess wide anti-microbial activities and are effective against pathogenic strains of gram-positive and gram-negative bacteria. They are widely used in the treatment of various infectious diseases e.g. malaria, urinary tract infections, respiratory tract infections etc. Based on their effectiveness against most of the bacteria, two novel sulfonamides (N-(2-methoxy phenyl)-4-methylbenzenesulfonamide and N-ethyl-4-methyl-N-(3-methyl phenyl)benzenesulfonamide) were synthesized. The compounds were characterized by FT-IR and elemental analyzer. Their anti-microbial activity was assessed and observed against gram-positive and gram-negative bacteria using disc diffusion method. They showed good anti-microbial activities.

  7. Identification of dfrA14 in two distinct plasmids conferring trimethoprim resistance in Actinobacillus pleuropneumoniae.

    Science.gov (United States)

    Bossé, Janine T; Li, Yanwen; Walker, Stephanie; Atherton, Tom; Fernandez Crespo, Roberto; Williamson, Susanna M; Rogers, Jon; Chaudhuri, Roy R; Weinert, Lucy A; Oshota, Olusegun; Holden, Matt T G; Maskell, Duncan J; Tucker, Alexander W; Wren, Brendan W; Rycroft, Andrew N; Langford, Paul R

    2015-08-01

    The objective of this study was to determine the distribution and genetic basis of trimethoprim resistance in Actinobacillus pleuropneumoniae isolates from pigs in England. Clinical isolates collected between 1998 and 2011 were tested for resistance to trimethoprim and sulphonamide. The genetic basis of trimethoprim resistance was determined by shotgun WGS analysis and the subsequent isolation and sequencing of plasmids. A total of 16 (out of 106) A. pleuropneumoniae isolates were resistant to both trimethoprim (MIC >32 mg/L) and sulfisoxazole (MIC ≥256 mg/L), and a further 32 were resistant only to sulfisoxazole (MIC ≥256 mg/L). Genome sequence data for the trimethoprim-resistant isolates revealed the presence of the dfrA14 dihydrofolate reductase gene. The distribution of plasmid sequences in multiple contigs suggested the presence of two distinct dfrA14-containing plasmids in different isolates, which was confirmed by plasmid isolation and sequencing. Both plasmids encoded mobilization genes, the sulphonamide resistance gene sul2, as well as dfrA14 inserted into strA, a streptomycin-resistance-associated gene, although the gene order differed between the two plasmids. One of the plasmids further encoded the strB streptomycin-resistance-associated gene. This is the first description of mobilizable plasmids conferring trimethoprim resistance in A. pleuropneumoniae and, to our knowledge, the first report of dfrA14 in any member of the Pasteurellaceae. The identification of dfrA14 conferring trimethoprim resistance in A. pleuropneumoniae isolates will facilitate PCR screens for resistance to this important antimicrobial. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  8. Establishment of a Fast Chemical Identification System for screening of counterfeit drugs of macrolide antibiotics.

    Science.gov (United States)

    Hu, Chang-Qin; Zou, Wen-Buo; Hu, Wang-Sheng; Ma, Xiao-Kang; Yang, Min-Zhi; Zhou, Shi-Lin; Sheng, Jin-Fang; Li, Yuan; Cheng, Shuang-Hong; Xue, Jing

    2006-01-23

    A Fast Chemical Identification System (FCIS) consisting of two colour reactions based on functional groups in molecules of macrolide antibiotics and two TLC methods was developed for screening of fake macrolide drugs. The active ingredients could be extracted from their oral preparations by absolute alcohol. Sulfuric acid reaction as a common reaction of macrolides was first used to distinguish the macrolides from other types of drugs and then 16-membered macrolides and 14-membered ones were distinguished by potassium permanganate reactions depending on the time of loss of colour in the test solution; after which a TLC method carried out on a GF(254) plate (5 cm x 10 cm) was chosen to further identification of the macrolides. The mobile phase A consisting of ethyl acetate, hexane and ammonia (100:15:15, v/v) was used for the identification of 14-membered macrolides, and the mobile phase B consisting of trichloromethane, methanol and ammonia (100:5:1, v/v) was used for the identification of 16-membered ones. A suspected counterfeit macrolide preparation can be identified within 40 min. The system can be used under different conditions and has the virtues of robustness, simplicity and speed.

  9. Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro

    Directory of Open Access Journals (Sweden)

    Toshikazu Shimane

    2001-01-01

    Full Text Available Background: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood.

  10. Thermodynamic study of the solubility of some sulfonamides in cyclohexane

    Directory of Open Access Journals (Sweden)

    Martínez Fleming

    2003-01-01

    Full Text Available The thermodynamic functions Gibbs energy, enthalpy and entropy of solution in cyclohexane, were evaluated from solubility data for a group of sulfonamides over the temperature range from 20.0 to 40.0 °C. The excess Gibbs energy and the activity coefficients of the solutes were also determined. The results are discussed in terms of solute-solvent interactions.

  11. Macrolides: A Canadian Infectious Disease Society Position Paper

    Directory of Open Access Journals (Sweden)

    S McKenna

    2001-01-01

    Full Text Available Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.

  12. Naegleria fowleri and N. lovaniensis: differences in sensitivity to trimethoprim and other antifolates.

    Science.gov (United States)

    Cerva, L

    1986-01-01

    The growth of Naegleria fowleri cultures in a BCS medium was not affected either by trimethoprim at 400 micrograms/ml or by aminopterine, 3,5-diaminopterine and methotrexate at 500 micrograms/ml. N. lovaniensis propagation in the same medium was inhibited with 10 micrograms/ml of trimethoprim, 50 micrograms/ml methotrexate and 100 micrograms/ml 3,5-diaminopteridine. Aminopterine was ineffective at a concentration of 500 micrograms/ml. The inhibitory effect of trimethoprim on N. lovaniensis cultures depended on the medium composition and could be neutralized by an addition of folic or tetrahydrofolic acids and a suspension of heat-killed Enterobacter aerogenes. Thymine, thymidine, hypoxantine and 2-amino-4-hydroxy-6-(tetrahydroxybutyl)-pteridine did not have an adverse effect. Trimethoprim activity in N. fowleri cultures could not be enhanced by the addition of Triton X-100 and Polymyxine B. Cryolyzate of N. fowleri amoebae did not influence the trimethoprim inhibition of N. lovaniensis cultures. Deviation in dihydrofolatereductase chemical structure or thymine dependency seems to be the probable explanation for N. fowleri antifolate resistance.

  13. Photocatalytic degradation of trimethoprim by metallic nanoparticles supported on TiO{sub 2}-P25

    Energy Technology Data Exchange (ETDEWEB)

    Oros-Ruiz, Socorro [Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, A.P. 70-186, Delegación Coyoacán, C.P. 04510 México, DF (Mexico); Zanella, Rodolfo, E-mail: rodolfo.zanella@ccadet.unam.mx [Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, A.P. 70-186, Delegación Coyoacán, C.P. 04510 México, DF (Mexico); Prado, Blanca [Instituto de Geología, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México, DF (Mexico)

    2013-12-15

    Highlights: • Photoactivity of TiO{sub 2} modified with metal NP evaluated in the degradation of trimethoprim. • The modification of TiO{sub 2} by gold and silver increases the mineralization of organic matter up to 80%. • The first study on the photocatalytic degradation of trimethoprim using TiO{sub 2} modified with metal NP. -- Abstract: The effect of Au, Ag, Cu and Ni nanoparticles deposited on TiO{sub 2}-P25 was studied on the photodegradation of trimethoprim, a commonly used antibiotic. The synthesized materials were characterized by ICP, EDS, XRD, BET, UV–vis, TEM and TPR. The metal loading was 0.5 wt.% and the average particle size was about 2 nm in all the studied samples. The deposition of metallic particles on TiO{sub 2}-P25 produces an enhancement of the activity of the bare semiconductor; when the degradation of trimethoprim was carried out by pure TiO{sub 2}-P25, the mineralization reached only 50% of the organic matter, while by using metallic nanoparticles deposited on TiO{sub 2}-P25, the mineralization of organic matter increased up to 80% for the same reaction conditions and reaction time. The evaluation of the photocatalytic activity was made for solutions containing trimethoprim in concentrations of 40 ppm under UV light irradiation using a lamp with primary emission at 254 nm and 2.2 mW/cm{sup 2}. It is shown that the ability of the photocatalyst to mineralize trimethoprim depends on the electron affinity and the electronegativity of the deposited metal.

  14. Design of amino acid sulfonamides as transition-state analogue inhibitors of arginase.

    Science.gov (United States)

    Cama, Evis; Shin, Hyunshun; Christianson, David W

    2003-10-29

    Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to form L-ornithine plus urea. Chiral L-amino acids bearing sulfonamide side chains have been synthesized in which the tetrahedral sulfonamide groups are designed to target bridging coordination interactions with the binuclear manganese cluster in the arginase active site. Syntheses of the amino acid sulfonamides have been accomplished by the amination of sulfonyl halide derivatives of (S)-(tert-butoxy)-[(tert-butoxycarbonyl)amino]oxoalkanoic acids. Amino acid sulfonamides with side chains comparable in length to that of L-arginine exhibit inhibition in the micromolar range, and the X-ray crystal structure of arginase I complexed with one of these inhibitors, S-(2-sulfonamidoethyl)-L-cysteine, has been determined at 2.8 A resolution. In the enzyme-inhibitor complex, the sulfonamide group displaces the metal-bridging hydroxide ion of the native enzyme and bridges the binuclear manganese cluster with an ionized NH(-) group. The binding mode of the sulfonamide inhibitor may mimic the binding of the tetrahedral intermediate and its flanking transition states in catalysis. It is notable that the ionized sulfonamide group is an excellent bridging ligand in this enzyme-inhibitor complex; accordingly, the sulfonamide functionality can be considered in the design of inhibitors targeting other binuclear metalloenzymes.

  15. Monoclonal antibodies against a sulfathiazole derivative for the immunochemical detection of sulfonamides

    NARCIS (Netherlands)

    Haasnoot, W.; Pre, Du J.; Cazemier, G.; Kemmers-Voncken, A.; Verheijen, R.; Jansen, B.J.M.

    2000-01-01

    To prepare monoclonal antibodies (mAbs) against the generic part of sulfonamides, a sulfathiazole derivative was chemically linked to carrier proteins in such a way that the aromatic amino group, common to all sulfonamides, was distal to the proteins. Four mice were immunized with the

  16. N-Hydroxy sulfonamides as new sulfenylating agents for the functionalization of aromatic compounds.

    Science.gov (United States)

    Wang, Fu-Xiang; Zhou, Shao-Da; Wang, Chengming; Tian, Shi-Kai

    2017-06-27

    An unprecedented use of N-hydroxy sulfonamides as sulfenylating agents has been established. In the presence of catalytic amounts of iodine and N-hydroxysuccinimide, N-hydroxy sulfonamides participated in sulfenylation with indoles, 7-azaindole, N-methyl pyrrole, and 2-naphthol to afford structurally diverse thioethers in moderate to excellent yields with very high regioselectivity.

  17. Metal-free I2O5-mediated direct construction of sulfonamides from thiols and amines.

    Science.gov (United States)

    Zhu, Minghui; Wei, Wei; Yang, Daoshan; Cui, Huanhuan; Wang, Leilei; Meng, Guoqing; Wang, Hua

    2017-06-07

    A simple and convenient method has been developed for the construction of sulfonamides via I 2 O 5 -mediated sulfonylation of amines with arylthiols. The present protocol provides an attractive approach to sulfonamides in moderate to good yields from readily accessible and easy to handle starting materials under mild and metal-free conditions.

  18. Multiplex PCR to identify macrolide resistance determinants in Mannheimia haemolytica and Pasteurella multocida.

    Science.gov (United States)

    Rose, Simon; Desmolaize, Benoit; Jaju, Puneet; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

    2012-07-01

    The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance to these drugs. Macrolide resistance in members of the family Pasteurellaceae is conferred by combinations of at least three genes: erm(42), which encodes a monomethyltransferase and confers a type I MLS(B) (macrolide, lincosamide, and streptogramin B) phenotype; msr(E), which encodes a macrolide efflux pump; and mph(E), which encodes a macrolide-inactivating phosphotransferase. Here, we describe a multiplex PCR assay that detects the presence of erm(42), msr(E), and mph(E) and differentiates between these genes. In addition, the assay distinguishes P. multocida from M. haemolytica by amplifying distinctive fragments of the 23S rRNA (rrl) genes. One rrl fragment acts as a general indicator of gammaproteobacterial species and confirms whether the PCR assay has functioned as intended on strains that are negative for erm(42), msr(E), and mph(E). The multiplex system has been tested on more than 40 selected isolates of P. multocida and M. haemolytica and correlated with MICs for the veterinary macrolides tulathromycin and tilmicosin, and the newer compounds gamithromycin and tildipirosin. The multiplex PCR system gives a rapid and robustly accurate determination of macrolide resistance genotypes and bacterial genus, matching results from microbiological methods and whole-genome sequencing.

  19. The evolution of substrate discrimination in macrolide antibiotic resistance enzymes.

    Science.gov (United States)

    Pawlowski, Andrew C; Stogios, Peter J; Koteva, Kalinka; Skarina, Tatiana; Evdokimova, Elena; Savchenko, Alexei; Wright, Gerard D

    2018-01-09

    The production of antibiotics by microbes in the environment and their use in medicine and agriculture select for existing and emerging resistance. To address this inevitability, prudent development of antibiotic drugs requires careful consideration of resistance evolution. Here, we identify the molecular basis for expanded substrate specificity in MphI, a macrolide kinase (Mph) that does not confer resistance to erythromycin, in contrast to other known Mphs. Using a combination of phylogenetics, drug-resistance phenotypes, and in vitro enzyme assays, we find that MphI and MphK phosphorylate erythromycin poorly resulting in an antibiotic-sensitive phenotype. Using likelihood reconstruction of ancestral sequences and site-saturation combinatorial mutagenesis, supported by Mph crystal structures, we determine that two non-obvious mutations in combination expand the substrate range. This approach should be applicable for studying the functional evolution of any antibiotic resistance enzyme and for evaluating the evolvability of resistance enzymes to new generations of antibiotic scaffolds.

  20. A unified approach to polyene macrolides: synthesis of candidin and nystatin polyols.

    Science.gov (United States)

    Kadota, Isao; Hu, Yueqing; Packard, Garrick K; Rychnovsky, Scott D

    2004-08-17

    Polyene macrolide antibiotics are naturally occurring antifungal agents. Members of this class include amphotericin B, which has been used widely to treat systemic fungal infections. A general synthetic strategy has been devised to prepare polyol chains associated with the polyene macrolides. Cyanohydrin acetonide alkylations were used to assemble the carbon skeleton, and a simple modification of the strategy allowed an advanced intermediate to be converted to either the candidin polyol or the nystatin polyol. The candidin polyol was further elaborated to a protected candidin aglycone. This strategy will be applicable to other members of the polyene macrolide natural products.

  1. Biodegradation of sulfonamides by Shewanella oneidensis MR-1 and Shewanella sp. strain MR-4.

    Science.gov (United States)

    Mao, Fei; Liu, Xiaohong; Wu, Kang; Zhou, Chen; Si, Youbin

    2018-04-01

    Because of extensive sulfonamides application in aquaculture and animal husbandry and the consequent increase in sulfonamides discharged into the environment, strategies to remediate sulfonamide-contaminated environments are essential. In this study, the resistance of Shewanella oneidensis MR-1 and Shewanella sp. strain MR-4 to the sulfonamides sulfapyridine (SPY) and sulfamethoxazole (SMX) were determined, and sulfonamides degradation by these strains was assessed. Shewanella oneidensis MR-1 and Shewanella sp. strain MR-4 were resistant to SPY and SMX concentrations as high as 60 mg/L. After incubation for 5 days, 23.91 ± 1.80 and 23.43 ± 2.98% of SPY and 59.88 ± 1.23 and 63.89 ± 3.09% of SMX contained in the medium were degraded by S. oneidensis MR-1 and Shewanella sp. strain MR-4, respectively. The effects of the initial concentration of the sulfonamides and initial pH of the medium on biodegradation, and the degradation of different sulfonamides were assessed. The products were measured by LC-MS; with SPY as a substrate, 2-AP (2-aminopyridine) was the main stable metabolite, and with SMX as a substrate, 3A5MI (3-amino-5-methyl-isoxazole) was the main stable metabolite. The co-occurrence of 2-AP or 3A5MI and 4-aminobenzenesulfonic acid suggests that the initial step in the biodegradation of the two sulfonamides is S-N bond cleavage. These results suggest that S. oneidensis MR-1 and Shewanella sp. strain MR-4 are potential bacterial resources for biodegrading sulfonamides and therefore bioremediation of sulfonamide-polluted environments.

  2. [Interaction Between Sulfonamide Antibiotics Fates and Chicken Manure Composting].

    Science.gov (United States)

    Lin, Hui; Wang, Jian-mei; Sun, Wan-chun; Fu, Jian-rong; Chen, Hong-jin; Ma, Jun-wei

    2016-05-15

    Based on aerobic manure composting with or without the addition of a mixture of sulfadimethoxine SM2 and sulfamonomethoxine SMM (1:1, m/m), changes in the physic-chemical properties of manure compost, the microbial community physiological profiles, the antibiotics concentration and the abundances of five antibiotic resistance genes (ARGs) during the composting were tracked. The results indicated that the introduction of sulfonamide antibiotics led to inhibition on the basal respiration of manure compost during the early composting period, delayed the formation of thermophilic temperature and reduced the conversion of nutrients such as organic matter, ammonia nitrogen and nitrate nitrogen. Meanwhile, the introduction of sulfonamide antibiotics dramatically affected the physiological profile of microbial community in manure in the middle stage of composting. HPLC-MS/MS results showed that both SMM and SM2 in manure were completely degraded within 14 days, while the degradation rate of SMM was faster than that of SM2. For both composting treatments with or without addition of exogenous antibiotics, the relative abundance of sull and sul2 showed an initial decline in the first 14 or 21 days and a slight increase thereafter. The addition of exogenous antibiotics showed insignificant enhancement on increasing the relative abundance of sul1 and IntI1 in manure, but resulted in an apparent increase in sul2 relative abundance. Although the fates of tetQ and tetW during composting were different from that of sulfonamide ARGs, the introduction of sulfonamide antibiotics into manure increased the relative abundance of tetracycline ARGs. Redundancy analysis indicated that composting temperature correlated negatively with sul1, sul2 and IntI1 relative abundance in manure but had no obvious relationship with tetQ and tetW relative abundance. All the ARGs detected in this work correlated negatively with C/N ratio and the nitrate nitrogen concentration of manure compost but

  3. Hazard of Sulfonamides and Detection Technology Research Progress

    Science.gov (United States)

    Jiang, Jiahui; Wang, Guangyu

    2017-12-01

    As a kind of widely used antibiotic with typical characteristics, sulfonamides have been greatly applied in clinical medicine for long time. It can’t be effectively treated by pollutant disposal system during pharmaceutical process and utilization and will be discharged into natural environment to be one of the antibiotics with great effect. This kind of substance is difficult to be biodegraded and will be easy to accumulate in the environment, generating huge eco-toxicological effect with significant mutagenicity and teratogenic effect. It is the severe threat for ecological balance, human health and drinking water safety. Its environmental behavior and detection technology attract extensive attention home and abroad.

  4. A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia.

    Science.gov (United States)

    Wade, J C; Schimpff, S C; Hargadon, M T; Fortner, C L; Young, V M; Wiernik, P H

    1981-04-30

    Fifty-three profoundly granulocytopenic patients with relapsed acute leukemia who were undergoing reinduction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or gentamicin plus nystatin for prevention of infections. The acquisition of new organisms per patient during the total study period was similar in both groups. Thirty-five symptomatic infections (five of which were bacteremias) occurred in patients receiving trimethoprim-sulfamethoxazole plus nystatin, whereas 31 infections (eight bacteremias) occurred in patients receiving gentamicin plus nystatin. Four deaths related to infection occurred in patients taking trimethoprim-sulfamethoxazole, and eight occurred in patients taking gentamicin. We conclude that trimethoprim-sulfamethoxazole plus nystatin was approximately as effective as gentamicin plus nystatin for prophylaxis against infection in relapsed acute leukemia. Furthermore, side effects were fewer and compliance was better with trimethoprim-sulfamethoxazole plus nystatin.

  5. Efficacy of ampicillin versus trimethoprim-sulfamethoxazole in a mouse model of lethal enterococcal peritonitis.

    OpenAIRE

    Chenoweth, C E; Robinson, K A; Schaberg, D R

    1990-01-01

    Lethal enterococcal peritonitis in mice was used to compare trimethoprim-sulfamethoxazole (TMP-SMX) therapy with ampicillin therapy. Peritoneal fluid showed a 10(3)-CFU decrease in enterococci with ampicillin compared with TMP-SMX. Mortality of the untreated mice was 100%, compared with 40% for ampicillin and 95% for TMP-SMX, despite adequately measured levels in serum and peritoneal fluid.

  6. Trimethoprim-sulfamethoxazole in children with chronic otitis media: a randomized comparison of costs and effects.

    NARCIS (Netherlands)

    Boonacker, C.W.; Veen, E.L. van der; Wilt, G.J. van der; Schilder, A.G.M.; Rovers, M.M.

    2008-01-01

    OBJECTIVE: To study the cost-effectiveness of a 6- to 12-week course of high-dose oral trimethoprim-sulfamethoxazole in children with chronic active otitis media (COM). STUDY DESIGN: Cost-effectiveness study including both direct and indirect costs alongside a randomized placebo-controlled trial.

  7. The analysis of tetracyclines, quinolones, macrolides, lincosamides, pleuromutilins, and sulfonamides in chicken feathers using UHPLC-MS/MS in order to monitor antibiotic use in the poultry sector

    NARCIS (Netherlands)

    Jansen, Larissa J.M.; Bolck, Yvette J.C.; Rademaker, Janneau; Zuidema, Tina; Berendsen, Bjorn J.A.

    2017-01-01

    In The Netherlands, all antibiotic treatments should be registered at the farm and in a central database. To enforce correct antibiotic use and registration, and to enforce prudent use of antibiotics, there is a need for methods that are able to detect antibiotic treatments. Ideally, such a method

  8. The analysis of tetracyclines, quinolones, macrolides, lincosamides, pleuromutilins, and sulfonamides in chicken feathers using UHPLC-MS/MS in order to monitor antibiotic use in the poultry sector.

    Science.gov (United States)

    Jansen, Larissa J M; Bolck, Yvette J C; Rademaker, Janneau; Zuidema, Tina; Berendsen, Bjorn J A

    2017-08-01

    In The Netherlands, all antibiotic treatments should be registered at the farm and in a central database. To enforce correct antibiotic use and registration, and to enforce prudent use of antibiotics, there is a need for methods that are able to detect antibiotic treatments. Ideally, such a method is able to detect antibiotic applications during the entire lifespan of an animal, including treatments administered during the first days of the animals' lives. Monitoring tissue, as is common practice, only provides a limited window of opportunity, as residue levels in tissue soon drop below measurable quantities. The analysis of feathers proves to be a promising tool in this respect. Furthermore, a qualitative confirmatory method was developed for the analyses of six major groups of antibiotics in ground chicken feathers, aiming for a detection limit as low as reasonably possible. The method was validated according to Commission Decision 2002/657/EC. All compounds comply with the criteria and, as a matter of fact, 58% of the compounds could also be quantified according to regulations. Additionally, we demonstrated that a less laborious method, in which whole feathers were analyzed, proved successful in the detection of applied antibiotics. Most compounds could be detected at levels of 2 μg kg -1 or below with the exception of sulfachloropyridazine, tylosin, and tylvalosin. This demonstrates the effectiveness of feather analysis to detect antibiotic use to allow effective enforcement of antibiotic use and prevent the illegal, off-label, and nonregistered use of antibiotics.

  9. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides

    DEFF Research Database (Denmark)

    Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf

    2012-01-01

    Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis...

  10. Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

    LENUS (Irish Health Repository)

    Murphy, D M

    2010-03-01

    The macrolides are a class of antibiotics widely prescribed in infectious disease. More recently, there has been considerable interest in potential indications for these agents, in addition to their simple antibacterial indications, in a number of lung pathophysiologies.

  11. Multiplex PCR To Identify Macrolide Resistance Determinants in Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Rose, Simon; Desmolaize, Benoit; Jaju, Puneet

    2012-01-01

    The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance...... to these drugs. Macrolide resistance in members of the family Pasteurellaceae is conferred by combinations of at least three genes: erm(42), which encodes a monomethyltransferase and confers a type I MLS(B) (macrolide, lincosamide, and streptogramin B) phenotype; msr(E), which encodes a macrolide efflux pump...... fragments of the 23S rRNA (rrl) genes. One rrl fragment acts as a general indicator of gammaproteobacterial species and confirms whether the PCR assay has functioned as intended on strains that are negative for erm(42), msr(E), and mph(E). The multiplex system has been tested on more than 40 selected...

  12. Nature nurtures the design of new semi-synthetic macrolide antibiotics.

    Science.gov (United States)

    Fernandes, Prabhavathi; Martens, Evan; Pereira, David

    2017-05-01

    Erythromycin and its analogs are used to treat respiratory tract and other infections. The broad use of these antibiotics during the last 5 decades has led to resistance that can range from 20% to over 70% in certain parts of the world. Efforts to find macrolides that were active against macrolide-resistant strains led to the development of erythromycin analogs with alkyl-aryl side chains that mimicked the sugar side chain of 16-membered macrolides, such as tylosin. Further modifications were made to improve the potency of these molecules by removal of the cladinose sugar to obtain a smaller molecule, a modification that was learned from an older macrolide, pikromycin. A keto group was introduced after removal of the cladinose sugar to make the new ketolide subclass. Only one ketolide, telithromycin, received marketing authorization but because of severe adverse events, it is no longer widely used. Failure to identify the structure-relationship responsible for this clinical toxicity led to discontinuation of many ketolides that were in development. One that did complete clinical development, cethromycin, did not meet clinical efficacy criteria and therefore did not receive marketing approval. Work on developing new macrolides was re-initiated after showing that inhibition of nicotinic acetylcholine receptors by the imidazolyl-pyridine moiety on the side chain of telithromycin was likely responsible for the severe adverse events. Solithromycin is a fourth-generation macrolide that has a fluorine at the 2-position, and an alkyl-aryl side chain that is different from telithromycin. Solithromycin interacts at three sites on the bacterial ribosome, has activity against strains resistant to older macrolides (including telithromycin), and is mostly bactericidal. Pharmaceutical scientists involved in the development of macrolide antibiotics have learned from the teachings of Professor Satoshi Omura and progress in this field was not possible without his endeavors.

  13. Molecular characterization of macrolide resistant Streptococcus pyogenes isolates from pharyngitis patients in Serbia.

    Science.gov (United States)

    Opavski, Natasa; Gajic, Ina; Borek, Anna L; Obszańska, Katarzyna; Stanojevic, Maja; Lazarevic, Ivana; Ranin, Lazar; Sitkiewicz, Izabela; Mijac, Vera

    2015-07-01

    A steady increase in macrolide resistance in Streptococcus pyogenes, group A streptococci (GAS) was reported in Serbia during 2004-2009 (9.9%). However, there are no data on the molecular epidemiology of pharyngeal macrolide resistance GAS (MRGAS) isolates. Therefore, the aims of this first nationwide study were to examine the prevalence of macrolide resistance in Serbian GAS and to determine their resistance phenotypes, genotypes and clonal relationships. Overall 3893 non-duplicate pharyngeal S. pyogenes isolates from outpatients with GAS infection were collected throughout country during 2008 and 2009. Among 486 macrolide resistant pharyngeal isolates collected, 103 were further characterized. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion test and PCR, respectively. Strain relatedness was determined by emm typing, multilocus sequence typing (MLST), multilocus variable tandem repeat analysis (MLVA), phage profiling (PP) and virulence factor profiling (VFP). Overall, macrolide resistance among GAS isolates in Serbia was 12.5%. M phenotype was the most common (71.8%), followed by iMLS (18.4%) and cMLS (9.7%). Three clonal complexes--emm75/mefA/ST49, emm12/mefA/ST36 and emm77/ermA/tetO/ST63 comprised over 90% of the tested strains. Although MLVA, PP and VFP distinguished 10, 20 and 12 different patterns, respectively, cluster analysis disclosed only small differences between strains which belonged to the same emm/ST type. Our data indicate dominance of three major internationally widely disseminated macrolide resistant clones and a high genetic homogeneity among the Serbian MRGAS population. Continued surveillance of macrolide resistance and clonal composition in MRGAS in Serbia in future is necessary to determine stability of MRGAS clones and to guide therapy strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The Current State of Macrolide Resistance in Campylobacter spp.: Trends and Impacts of Resistance Mechanisms.

    Science.gov (United States)

    Bolinger, Hannah; Kathariou, Sophia

    2017-06-15

    Campylobacter spp., especially Campylobacter jejuni and C. coli , are leading bacterial foodborne pathogens worldwide. In the United States, an estimated 0.8 million cases of campylobacteriosis occur annually, mostly involving C. jejuni Campylobacteriosis is generally self-limiting, but in severe cases, treatment with antibiotics may be mandated. The increasing incidence of fluoroquinolone resistance in Campylobacter has rendered macrolides such as erythromycin and azithromycin the drugs of choice for human campylobacteriosis. The prevalence of macrolide resistance in C. jejuni remains low, but macrolide resistance can be common in C. coli Substitutions in the 23S rRNA gene, specifically A2075G, and less frequently A2074C/G, remain the most common mechanism for high-level resistance to macrolides. In C. jejuni , resistance mediated by such substitutions is accompanied by a reduced ability to colonize chickens and other fitness costs, potentially contributing to the low incidence of macrolide resistance. Interestingly, similar fitness impacts have not been noted in C. coli Also noteworthy is a novel mechanism first reported in 2014 for a C. coli isolate from China and mediated by erm (B) harbored on multidrug resistance genomic islands. The incidence of erm (B) appears to reflect clonal expansion of certain strains, and whole-genome sequencing has been critical to the elucidation of erm (B)-associated macrolide resistance in Campylobacter spp. With the exception of one report from Spain, erm (B)-mediated macrolide resistance has been restricted to Campylobacter spp., mostly C. coli , of animal and human origin from China. If erm (B)-mediated macrolide resistance does not confer fitness costs in C. jejuni , the range of this gene may expand in C. jejuni , threatening to compromise treatment effectiveness for severe campylobacteriosis cases. Copyright © 2017 American Society for Microbiology.

  15. A unified approach to polyene macrolides: Synthesis of candidin and nystatin polyols

    OpenAIRE

    Kadota, Isao; Hu, Yueqing; Packard, Garrick K.; Rychnovsky, Scott D.

    2004-01-01

    Polyene macrolide antibiotics are naturally occurring antifungal agents. Members of this class include amphotericin B, which has been used widely to treat systemic fungal infections. A general synthetic strategy has been devised to prepare polyol chains associated with the polyene macrolides. Cyanohydrin acetonide alkylations were used to assemble the carbon skeleton, and a simple modification of the strategy allowed an advanced intermediate to be converted to either the candidin polyol or th...

  16. Adsorptive removal of sulfonamide antibiotics in livestock urine using the high-silica zeolite HSZ-385.

    Science.gov (United States)

    Fukahori, S; Fujiwara, T; Funamizu, N; Matsukawa, K; Ito, R

    2013-01-01

    The adsorptive removal of seven sulfonamide antibiotics using the high-silica zeolite HSZ-385 from distilled water, synthetic urine and real porcine urine was investigated. The pH greatly affected the adsorption efficiency, and the amounts of all sulfonamide antibiotics adsorbed on HSZ-385 decreased at alkaline conditions compared with that at neutral conditions. During storage, the pH and ammonium-ion concentration increased with urea hydrolysis for porcine urine. We clarified that the adsorption efficiency of sulfonamides in synthetic urine was equivalent to that in distilled water, suggesting that adsorption behavior was not affected by coexistent ions. HSZ-385 could adsorb sulfonamide antibiotics in real porcine urine even though the non-purgeable organic carbon concentration of porcine urine was 4-7 g/L and was two orders of magnitude higher than those of sulfonamides (10 mg/L each). Moreover, the adsorption of sulfonamides reached equilibrium within 15 min, suggesting that HSZ-385 is a promising adsorbent for removing sulfonamides from porcine urine.

  17. Enzymatic Transformation and Bonding of Sulfonamide Antibiotics to Model Humic Substances

    Directory of Open Access Journals (Sweden)

    J. Schwarz

    2015-01-01

    Full Text Available Sulfonamides are consumed as pharmaceutical antibiotics and reach agricultural soils with excreta used as fertilizer. Subsequently, nonextractable residues rapidly form in soil, which has been researched in a couple of studies. To further elucidate conditions, strength, and mechanisms of the fixation to soil humic substances, three selected sulfonamides were investigated using the biochemical oligomerization of substituted phenols as a model for the humification process. Catechol, guaiacol, and vanillin were enzymatically reacted using laccase from Trametes versicolor. In the presence of the substituted phenols alone, the concentration of sulfonamides decreased. This decrease was even more pronounced when additional laccase was present. Upon the enzymatic oligomerization of the substituted phenols to a humic-like structure the sulfonamides were sorbed, transformed, sequestered, and nonextractable bound. Sulfonamides were transformed depending on their molecular properties. Fractions of different bonding strength were determined using a sequential extraction procedure. Isolated nonextractable products were analyzed by chromatographic, spectroscopic, and calorimetric methods to identify coupling and bonding mechanisms of the sulfonamides. Differential scanning calorimetry measurements suggested cross-linking of such incorporated sulfonamides in humic oligomers. Nuclear magnetic resonance spectroscopy measurements showed clear differences between the vanillin-sulfapyridine oligomer and the parent sulfapyridine indicating bound residue formation through covalent binding.

  18. Transformation of aqueous sulfonamides under horseradish peroxidase and characterization of sulfur dioxide extrusion products from sulfadiazine.

    Science.gov (United States)

    Yang, Lihua; Shi, Yang; Li, Jinjin; Fang, Ling; Luan, Tiangang

    2018-06-01

    The potential of horseradish peroxidase (HRP) to catalyze the removal of sulfonamides from water and the effects of different H 2 O 2 and HRP concentrations were investigated. Six sulfonamides, each with a five- or six-membered heterocyclic group, including sulfamethoxazole (SMX), sulfathiazole (STZ), sulfapyridine (SPD), sulfadiazine (SDZ), sulfamerazine (SMR) and sulfamethoxypyridazine (SMP) were selected as target compounds. All sulfonamides exhibit a pseudo-first-order dependence of the concentration versus the reaction time. The decay rate (k, h -1 ) of the six sulfonamides spiked individually exhibit a trend following the order of STZ > SMP, SPD > SMR > SDZ » SMX. When spiked together, the coexistent sulfonamides might act as mediators for the enhancement of SMX removal and as competitors for the decreased removal of most sulfonamides. Moreover, six transformation products of SDZ are identified by the Thermo Scientific LTQ Orbitrap Elite technique. SDZ transformation involves two steps: one is the Smiles re-arrangement of the structure, and the other is oxidation and sulfur dioxide extrusion. This study is the first to report the removal dynamics of sulfonamides in HRP-catalyzed reactions and the identified products of SDZ. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Impaired Fitness and Transmission of Macrolide-Resistant Campylobacter jejuni in Its Natural Host

    Science.gov (United States)

    Luangtongkum, Taradon; Shen, Zhangqi; Seng, Virginia W.; Sahin, Orhan; Jeon, Byeonghwa; Liu, Peng

    2012-01-01

    Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter has become a concern for public health. To facilitate the control of macrolide-resistant Campylobacter, it is necessary to understand if macrolide resistance affects the fitness and transmission of Campylobacter in its natural host. In this study we conducted pairwise competitions and comingling experiments in chickens using clonally related and isogenic C. jejuni strains, which are either susceptible or resistant to erythromycin (Ery). In every competition pair, Ery-resistant (Eryr) Campylobacter was consistently outcompeted by the Ery-susceptible (Erys) strain. In the comingling experiments, Eryr Campylobacter failed to transmit to chickens precolonized by Erys Campylobacter, while isogenic Erys Campylobacter was able to transmit to and establish dominance in chickens precolonized by Eryr Campylobacter. The fitness disadvantage was linked to the resistance-conferring mutations in the 23S rRNA. These findings clearly indicate that acquisition of macrolide resistance impairs the fitness and transmission of Campylobacter in chickens, suggesting that the prevalence of macrolide-resistant C. jejuni will likely decrease in the absence of antibiotic selection pressure. PMID:22183170

  20. Molecular dynamics-assisted pharmacophore modeling of caspase-3-isatin sulfonamide complex: Recognizing essential intermolecular contacts and features of sulfonamide inhibitor class for caspase-3 binding.

    Science.gov (United States)

    Kumar, Sivakumar Prasanth; Patel, Chirag N; Jha, Prakash C; Pandya, Himanshu A

    2017-12-01

    The identification of isatin sulfonamide as a potent small molecule inhibitor of caspase-3 had fuelled the synthesis and characterization of the numerous sulfonamide class of inhibitors to optimize for potency. Recent works that relied on the ligand-based approaches have successfully shown the regions of optimizations for sulfonamide scaffold. We present here molecular dynamics-based pharmacophore modeling of caspase-3-isatin sulfonamide crystal structure, to elucidate the essential non-covalent contacts and its associated pharmacophore features necessary to ensure caspase-3 optimal binding. We performed 20ns long dynamics of this crystal structure to extract global conformation states and converted into structure-based pharmacophore hypotheses which were rigorously validated using an exclusive focussed library of experimental actives and inactives of sulfonamide class by Receiver Operating Characteristic (ROC) statistic. Eighteen structure-based pharmacophore hypotheses with better sensitivity and specificity measures (>0.6) were chosen which collectively showed the role of pocket residues viz. Cys163 (S 1 sub-site; required for covalent and H bonding with Michael acceptor of inhibitors), His121 (S 1 ; π stack with bicyclic isatin moiety), Gly122 (S 1 ; H bond with carbonyl oxygen) and Tyr204 (S 2 ; π stack with phenyl group of the isatin sulfonamide molecule) as stringent binding entities for enabling caspase-3 optimal binding. The introduction of spatial pharmacophore site points obtained from dynamics-based pharmacophore models in a virtual screening strategy will be helpful to screen and optimize molecules belonging to sulfonamide class of caspase-3 inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. When other separation techniques fail: compound-specific carbon isotope ratio analysis of sulfonamide containing pharmaceuticals by high-temperature-liquid chromatography-isotope ratio mass spectrometry.

    Science.gov (United States)

    Kujawinski, Dorothea M; Zhang, Lijun; Schmidt, Torsten C; Jochmann, Maik A

    2012-09-18

    Compound-specific isotope analysis (CISA) of nonvolatile analytes has been enabled by the introduction of the first commercial interface to hyphenate liquid chromatography with an isotope ratio mass spectrometer (LC-IRMS) in 2004, yet carbon isotope analysis of unpolar and moderately polar compounds is still a challenging task since only water as the eluent and no organic modifiers can be used to drive the separation in LC. The only way to increase the elution strength of aqueous eluents in reversed phase LC is the application of high temperatures to the mobile and stationary phases (HT-LC-IRMS). In this context we present the first method to determine carbon isotope ratios of pharmaceuticals that cannot be separated by already existing separation techniques for LC-IRMS, such as reversed phase chromatography at normal temperatures, ion-chromatography, and mixed mode chomatography. The pharmaceutical group of sulfonamides, which is generally mixed with trimethoprim in pharmaceutical products, has been chosen as probe compounds. Substance amounts as low as 0.3 μg are sufficient to perform a precise analysis. The successful applicability and reproducibility of this method is shown by the analysis of real pharmaceutical samples. The method provides the first tool to study the pharmaceutical authenticity as well as degradation and mobility of such substances in the environment by using the stable isotopic signature of these compounds.

  2. Occurrence and fate of dissolved and particulate antimicrobials in municipal wastewater treatment

    OpenAIRE

    Senta, Ivan; Terzić, Senka; Ahel, Marijan

    2013-01-01

    Comprehensive study on the occurrence and fate of several classes of antimicrobials, including sulfonamides, trimethoprim, fluoroquinolones and macrolides, in Croatian municipal wastewaters was performed using an integrated approach, which comprised analysis of both dissolved and particulate fractions. A nation-wide screening showed ubiquitous occurrence of human-use antimicrobials in raw wastewater samples with the total concentrations ranging from 2 to 20 μg/L, while veterinary antimicrobia...

  3. Chemoselective Deprotection of Sulfonamides Under Acidic Conditions: Scope, Sulfonyl Group Migration, and Synthetic Applications.

    Science.gov (United States)

    Javorskis, Tomas; Orentas, Edvinas

    2017-12-15

    Chemoselective acidic hydrolysis of sulfonamides with trifluoromethanesulfonic acid has been evaluated as a deprotection method and further extended to more complex synthetic applications. In contrast to conventional troublesome sulfonamide hydrolysis, a near-stoichiometric amount of acid was found to be sufficient to bring about efficient deprotection of various neutral or electron-deficient N-arylsulfonamides, whereas electron-rich substrates provided sulfonyl group migration products. The deprotection method developed is fully selective for N-arylsulfonamides, and the possibility to discriminate among various different sulfonamides is demonstrated.

  4. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study.

    Science.gov (United States)

    Antoniou, Tony; Gomes, Tara; Mamdani, Muhammad M; Yao, Zhan; Hellings, Chelsea; Garg, Amit X; Weir, Matthew A; Juurlink, David N

    2011-09-12

    To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone. Population based nested case-control study. Ontario, Canada, from 1 April 1992 to 1 March 2010. Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date. Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia. During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was

  5. Inhibitory effects of the macrolide antimicrobial tylosin on anaerobic treatment.

    Science.gov (United States)

    Shimada, Toshio; Zilles, Julie L; Morgenroth, Eberhard; Raskin, Lutgarde

    2008-09-01

    A laboratory-scale anaerobic sequencing batch reactor (ASBR) was operated using a glucose-based synthetic wastewater to study the effects of tylosin, a macrolide antimicrobial commonly used in swine production, on treatment performance. The experimental period was divided into three consecutive phases with different influent tylosin concentrations (0, 1.67, and 167 mg/L). The addition of 1.67 mg/L tylosin to the reactor had negligible effects on the overall treatment performance, that is, total methane production and effluent chemical oxygen demand did not change significantly (P tylosin was added. The addition of 167 mg/L tylosin to the reactor resulted in a gradual decrease in methane production and the accumulation of propionate and acetate. Subsequent inhibition of methanogenesis was attributed to a decrease in the pH of the reactor. After the addition of 167 mg/L tylosin to the reactor, an initial decrease in the rate of glucose uptake during the ASBR cycle followed by a gradual recovery was observed. In batch tests, the specific biogas production with the substrate butyrate was completely inhibited in the presence of tylosin. This study indicated that tylosin inhibited propionate- and butyrate-oxidizing syntrophic bacteria and fermenting bacteria resulting in unfavorable effects on methanogenesis.

  6. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition.

    Science.gov (United States)

    Kobayashi, Yoshiki; Wada, Hiroo; Rossios, Christos; Takagi, Dai; Higaki, Manabu; Mikura, Shin'ichiro; Goto, Hajime; Barnes, Peter J; Ito, Kazuhiro

    2013-04-01

    Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNFα (tumor necrosis factor α) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-κB (nuclear factor-κB) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFα/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNFα release and MMP9 activity in PBMC from COPD patients at 10 µM, which is 10 times more potent than the other macrolides tested. Activated NF-κB by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future.

  7. DESIGN, SYNTHESIS, AND APPLICATION OF THE TRIMETHOPRIM-BASED CHEMICAL TAG FOR LIVE CELL IMAGING

    Science.gov (United States)

    Jing, Chaoran; Cornish, Virginia W.

    2013-01-01

    Over the past decade chemical tags have been developed to complement the use of fluorescent proteins in live cell imaging. Chemical tags retain the specificity of protein labeling achieved with fluorescent proteins through genetic encoding, but provide smaller, more robust tags and modular use of organic fluorophores with high photon-output and tailored functionalities. The trimethoprim-based chemical tag (TMP-tag) was initially developed based on the high affinity interaction between E.coli dihydrofolatereductase and the antibiotic trimethoprim and subsequently rendered covalent and fluorogenic via proximity-induced protein labeling reactions. To date, the TMP-tag is one of the few chemical tags that enable intracellular protein labeling and high-resolution live cell imaging. Here we describe the general design, chemical synthesis, and application of TMP-tag for live cell imaging. Alternative protocols for synthesizing and using the covalent and the fluorogenic TMP-tags are also included. PMID:23839994

  8. Bis(sulfonamide) transmembrane carriers allow pH-gated inversion of ion selectivity.

    Science.gov (United States)

    Roy, Arundhati; Biswas, Oindrila; Talukdar, Pinaki

    2017-03-09

    Bis(sulfonamide) based synthetic carriers are reported for inversion of ion selectivity upon deviation of pH within a narrow window. A liposomal membrane potential is also generated when potassium ions are passively transported by these carriers.

  9. Sulfonamide chalcones: Synthesis and in vitro exploration for therapeutic potential against Brugia malayi.

    Science.gov (United States)

    Bahekar, Sandeep P; Hande, Sneha V; Agrawal, Nikita R; Chandak, Hemant S; Bhoj, Priyanka S; Goswami, Kalyan; Reddy, M V R

    2016-11-29

    Keeping in mind the immense biological potential of chalcones and sulfonamide scaffolds, a library of sulfonamide chalcones has been synthesized and evaluated for in vitro antifilarial assay against human lymphatic filarial parasite Brugia malayi. Experimental evidence showcased for the first time the potential of some sulfonamide chalcones as effective and safe antifilarial lead molecules against human lymphatic filarial parasite B. malayi. Sulfonamide chalcones 4d, 4p, 4q, 4t and 4aa displayed the significantly wide therapeutic window. Particularly chalcones with halogen substitution in aromatic ring proved to be potent antifilarial agents against Brugia malayi. Sulphonamide chalcones with lipophilic methyl moiety (4q and 4aa) at para position of terminal phenyl rings of compounds were found to have remarkable antifilarial activities with therapeutic efficacy. Observed preliminary evidence of apoptosis by effective chalcone derivatives envisaged its fair possibility to inhibit folate pathway with consequent defect in DNA synthesis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Polymorphism, Intermolecular Interactions, and Spectroscopic Properties in Crystal Structures of Sulfonamides.

    Science.gov (United States)

    Sainz-Díaz, C Ignacio; Francisco-Márquez, Misaela; Soriano-Correa, Catalina

    2018-01-01

    The antibiotics family of sulfonamides has been used worldwide intensively in human therapeutics and farm livestock during decades. Intermolecular interactions of these sulfamides are important to understand their bioactivity and biodegradation. These interactions are also responsible for their supramolecular structures. The intermolecular interactions in the crystal polymorphs of the sulfonamides, sulfamethoxypyridazine, and sulfamethoxydiazine, as models of sulfonamides, have been studied by using quantum mechanical calculations. Different conformations in the sulphonamide molecules have been detected in the crystal polymorphs. Several intermolecular patterns have been studied to understand the molecular packing behavior in these antibiotics. Strong intermolecular hydrogen bonds and π-π interactions are the main driving forces for crystal packing in these sulfonamides. Different stability between polymorphs can explain the experimental behavior of these crystal forms. The calculated infrared spectroscopy frequencies explain the main intermolecular interactions in these crystals. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Synthesis and antibacterial activity of sulfonamides. SAR and DFT studies

    Science.gov (United States)

    Boufas, Wahida; Dupont, Nathalie; Berredjem, Malika; Berrezag, Kamel; Becheker, Imène; Berredjem, Hajira; Aouf, Nour-Eddine

    2014-09-01

    A series of substituted sulfonamide derivatives were synthesized from chlorosulfonyl isocyanate (CSI) in tree steps (carbamoylation, sulfamoylation and deprotection). Antibacterial activity in vitro of some newly formed compounds investigated against clinical strains Gram-positive and Gram-negative: Escherichia coli and Staphylococcus aureus applying the method of dilution and minimal inhibition concentration (MIC) methods. These compounds have significant bacteriostatic activity with totalities of bacterial strains used. DFT calculations with B3LYP/6-31G(d) level have been used to analyze the electronic and geometric characteristics deduced for the stable structure of three compounds presenting conjugation between a nitrogen atom N through its lone pair and an aromatic ring next to it. The principal quantum chemical descriptors have been correlated with the antibacterial activity.

  12. Uptake of Sulfadiazine Sulfonamide from Water by Clinoptilolite

    Directory of Open Access Journals (Sweden)

    Zhaohui Li

    2013-01-01

    Full Text Available The interactions between sulfadiazine (SDZ, a sulfonamide antibiotic, and clinoptilolite, a hydrophilic zeolite, were investigated under batch experimental conditions. The uptake of SDZ on the zeolite followed a linear sorption isotherm under neutral pH conditions. Higher SDZ uptake on the zeolite was observed when solution pH was below the or above the values of SDZ, while minimal SDZ uptake was observed when the solution pH was between the and values of SDZ. These observations suggested that hydrophobic interaction between SDZ and the zeolite was minimal due to the hydrophilic nature of the substrate. Electrostatic interactions and ion bridging were attributed to the elevated SDZ uptake under low and high pH conditions. As SDZ had a low value, the hydrophilic nature of the substrate prevented extensive uptake of SDZ, which could contribute to its extensive detection in the environment, including surface water and wastewater.

  13. An outbreak of trimethoprim/sulfamethoxazole-resistant Stenotrophomonas maltophilia meningitis associated with neuroendoscopy

    OpenAIRE

    Ching-Hsun Wang; Shih-Wei Hsu; Tung-Han Tsai; Ning-Chi Wang

    2014-01-01

    Stereotactic aspiration by neuroendoscopy for treatment of deep-seated intracranial hematomas is widely accepted because this procedure is minimally invasive and thereby reduces the probability of iatrogenic brain damage. Herein, we describe an outbreak of trimethoprim/sulfamethoxazole (TMP/SXT)-resistant Stenotrophomonas maltophilia meningitis, possibly from a contaminated neuroendoscopy, and review the previous use of antimicrobial therapies for this condition without TMP/SXT. This is the f...

  14. Regional dissemination of a trimethoprim-resistance gene cassette via a successful transposable element.

    Directory of Open Access Journals (Sweden)

    Amy S Labar

    Full Text Available Antimicrobial resistance is a growing international problem. We observed a 50% increase in the prevalence of trimethoprim resistance among fecal Escherichia coli from healthy Nigerian students between 1998 and 2005, a trend to increase that continued in 2009.A PCR-based screen revealed that 131 (43.1% of isolates obtained in Nigeria in 2005 and 2009 carried integron-borne dfrA cassettes. In the case of 67 (51.1% of these isolates, the cassette was a class 1-integron-borne dfrA7 gene, which has been reported at high prevalence from E. coli isolates from other parts of Africa. Complete sequencing of a 27 Kb dfrA7-bearing plasmid from one isolate located the dfrA7 gene within a Tn21-type transposon. The transposon also contained an IS26-derived bla/sul/str element, encoding resistance to β-lactams, sulphonamides and streptomycin, and mercury resistance genes. Although the plasmid backbone was only found in 12 (5.8% of trimethoprim-resistant isolates, dfrA7 and other transposon-borne genes were detected in 14 (16.3% and 32 (26.3% of trimethoprim resistant isolates collected in Nigeria in 2005 and 2009, respectively. Additionally, 37 (19.3% of trimethoprim-resistant E. coli isolates collected between 2006 and 2008 from Ghana were positive for the dfrA7 and a transposon marker, but only 4 (2.1% harbored the plasmid backbone.Our data point to transposition as a principal mechanism for disseminating dfrA7 among E. coli from Nigeria and Ghana. On-going intensive use of the affordable broad-spectrum antibacterials is likely to promote selective success of a highly prevalent transposable element in West Africa.

  15. Selective Access to Heterocyclic Sulfonamides and Sulfonyl Fluorides via a Parallel Medicinal Chemistry Enabled Method.

    Science.gov (United States)

    Tucker, Joseph W; Chenard, Lois; Young, Joseph M

    2015-11-09

    A sulfur-functionalized aminoacrolein derivative is used for the efficient and selective synthesis of heterocyclic sulfonyl chlorides, sulfonyl fluorides, and sulfonamides. The development of a 3-step parallel medicinal chemistry (PMC) protocol for the synthesis of pyrazole-4-sulfonamides effectively demonstrates the utility of this reagent. This reactivity was expanded to provide rapid access to other heterocyclic sulfonyl fluorides, including pyrimidines and pyridines, whose corresponding sulfonyl chlorides lack suitable chemical stability.

  16. Quantitative LC/MS-MS determination of sulfonamides and some other antibiotics in honey.

    Science.gov (United States)

    Kaufmann, Anton; Roth, Sven; Ryser, Bianca; Widmer, Mirjam; Guggisberg, Domink

    2002-01-01

    A simple and rapid method was developed for the determination of 20 antibiotics (sulfonamides, tetacyclines, and flumequine) in honey by liquid chromatography tandem mass spectrometry. The proposed method is sensitive (limit of detection 0.5 to 10 ppb for the various antibiotics) and selective. A hydrolysis step ensures the liberation of sugar-bound sulfonamides. The approach has been used to analyze some 300 honey samples. A number of them were found to have exceeded the Swiss limit of 50 ppb.

  17. Oxidation of Sulfonamides in Aqueous Solution by UV-TiO2-Fe(VI

    Directory of Open Access Journals (Sweden)

    Yan Ma

    2015-01-01

    Full Text Available The photocatalytic degradation of sulfonamides in aqueous TiO2 suspension under UV irradiation has been investigated using potassium ferrate as electron acceptors. The results showed that the stability of Fe(VI is dependent on pH significantly, and the stability reduces obviously in the presence of UV-TiO2. The experiments indicated that Fe(VI could effectively scavenge the conduction band electrons from the surface of TiO2. The photocatalytic oxidation of sulfonamides with Fe(VI was found to be much faster than that without Fe(VI. The SD, SM, and SMX concentration was greatly reduced by 89.2%, 83.4%, and 82.0%, respectively, after 10 min with UV-TiO2-Fe(VI, comparing to 65.2%, 66.0%, and 71.9%, respectively, with Fe(VI only in the dark and 71.3%, 72.7%, and 76.0%, respectively, with UV-TiO2. The pH value of solution significantly influenced the sulfonamides degradation in UV-TiO2-Fe(VI system. The degradation amount of sulfonamides after 10 min was a maximum at pH 7. The intermediate products of sulfonamides oxidation by UV-TiO2-Fe(VI were analysed by LC-HESI-MS-MS and the results suggested that a majority of sulfonamides turned into large-molecule products without complete mineralization.

  18. Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women

    OpenAIRE

    McMurdo, Marion E. T.; Argo, Ishbel; Phillips, Gabby; Daly, Fergus; Davey, Peter

    2008-01-01

    Objectives To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women. Patients and methods One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months. Trial registration: ISRCTN80031108. Results Thirty-nine of 137 participants (28%) had an antibiotic-treat...

  19. Acquired resistance to macrolides inPseudomonas aeruginosafrom cystic fibrosis patients.

    Science.gov (United States)

    Mustafa, Muhammad-Hariri; Khandekar, Shaunak; Tunney, Michael M; Elborn, J Stuart; Kahl, Barbara C; Denis, Olivier; Plésiat, Patrick; Traore, Hamidou; Tulkens, Paul M; Vanderbist, Francis; Van Bambeke, Françoise

    2017-05-01

    Cystic fibrosis (CF) patients receive chronic treatment with macrolides for their antivirulence and anti-inflammatory properties. We, however, previously showed that Pseudomonas aeruginosa , considered as naturally resistant to macrolides, becomes susceptible when tested in a eukaryotic medium rather than a conventional broth.We therefore looked for specific macrolide resistance determinants in 333 CF isolates from four European CF centres in comparison with 48 isolates from patients suffering from hospital-acquired pneumonia (HAP).Minimum inhibitory concentrations (MICs) of macrolides and ketolides measured in eukaryotic medium (RPMI-1640) were higher towards CF than HAP isolates. Gene sequencing revealed mutations at three positions (2045, 2046 and 2598) in domain V of 23S rRNA of 43% of sequenced CF isolates, but none in HAP isolates. Enzymes degrading extracellular polymeric substances also reduced MICs, highlighting a role of the mucoid, biofilm-forming phenotype in resistance. An association between high MICs and chronic azithromycin administration was evidenced, which was statistically significant for patients infected by the Liverpool Epidemic Strain.Thus, ribosomal mutations are highly prevalent in CF isolates and may spread in epidemic clones, arguing for prudent use of oral macrolides in these patients. Measuring MICs in RPMI-1640 could be easily implemented in microbiology laboratories to phenotypically detect resistance. Copyright ©ERS 2017.

  20. Conformation of macrolides antibiotics bound to ribosomes as determined from transferred nuclear Overhauser effect spectroscopy

    Science.gov (United States)

    Bertho, G.; Ladam, P.; Gharbi-Benarous, J.; Delaforge, M.; Girault, J.-P.

    1998-02-01

    The ribosomal bound conformation of 14-membered-ring macrolides roxithromycin, erythromycin A and their methylated derivatives has been elucidated from study of the macrolide-ribosome interactions using transferred nuclear Overhauser effect (TRNOE). Only one specific conformation is preferred in the bound state. The bioactive macrolide antibiotics studied displayed a strong NMR response, while their inactive major metabolites displayed blank TRNOESY spectrum. TRNOE analysis established correlation between the bound state conformation of these active compounds and the major conformation (A1a) in solution. La conformation liée au ribosome des antibiotiques macrolides tels que la roxithromycine, l'érythromycine A et leurs dérivés méthylés a été déterminée en utilisant l'expérience d'effet nucléaire Overhauser transféré (TRNOE). Une seule conformation spécifique est préférée dans l'état lié. Les antibiotiques macrolides actifs étudiés donnent une bonne réponse RMN alors que leurs métabolites, qui sont inactifs, présentent un spectre TRNOESY vide. L'analyse des TRNOEs établit une corrélation entre la conformation liée de ses composés actifs et la conformation (A1a) majoritaire en solution.

  1. Macrolides and respiratory infection in critically ill patients: what is the next step?

    Science.gov (United States)

    Lisboa, Thiago; Salluh, Jorge I F; Friedman, Gilberto

    2016-02-01

    Several observational studies as well as experimental data suggest that the use of macrolides is associated with better outcomes in patients with severe pneumonia. In severe community acquired pneumonia (SCAP), data demonstrate a benefit of combination therapy, including a beta-lactam plus a macrolide or floroquinolone, at least in the subgroup of patients with critical disease. Such combination seems to have a more significant impact in those with increased disease severity, particularly in those presenting with shock. In addition, data suggest that not all combinations are the same, and SCAP patients receiving combination therapy with macrolides have lower mortality than patients receiving combination with fluoroquinolones. Better results could be associated with a potential immunomodulatory effect of macrolides as well as inhibition to bacterial growth and virulence factors expression (e.g. Streptococcus pneumoniae pneumolysin). Additionally, recent studies try to incorporate these drugs to our therapeutic options in patients with other sepsis causes (e.g. nosocomial pneumonia) and pathogens (e.g. Pseudomonas aeruginosa). In this review, we will assess these issues, discussing the available evidence on macrolides use and highlighting potential research questions to be assessed on this field.

  2. Macrolides and lincosamides in cattle and pigs: use and development of antimicrobial resistance.

    Science.gov (United States)

    Pyörälä, Satu; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Greko, Christina; Moreno, Miguel A; Pomba, M Constança Matias Ferreira; Rantala, Merja; Ružauskas, Modestas; Sanders, Pascal; Threlfall, E John; Torren-Edo, Jordi; Törneke, Karolina

    2014-05-01

    Macrolides and lincosamides are important antibacterials for the treatment of many common infections in cattle and pigs. Products for in-feed medication with these compounds in combination with other antimicrobials are commonly used in Europe. Most recently approved injectable macrolides have very long elimination half-lives in both pigs and cattle, which allows once-only dosing regimens. Both in-feed medication and use of long-acting injections result in low concentrations of the active substance for prolonged periods, which causes concerns related to development of antimicrobial resistance. Acquired resistance to macrolides and lincosamides among food animal pathogens, including some zoonotic bacteria, has now emerged. A comparison of studies on the prevalence of resistance is difficult, since for many micro-organisms no agreed standards for susceptibility testing are available. With animal pathogens, the most dramatic increase in resistance has been seen in the genus Brachyspira. Resistance towards macrolides and lincosamides has also been detected in staphylococci isolated from pigs and streptococci from cattle. This article reviews the use of macrolides and lincosamides in cattle and pigs, as well as the development of resistance in target and some zoonotic pathogens. The focus of the review is on European conditions. Copyright © 2014. Published by Elsevier Ltd.

  3. August 2014 Phoenix pulmonary journal club: the use of macrolide antibiotics in chronic respiratory disease

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2014-08-01

    Full Text Available No abstract available. Article truncated after 150 words. This month's journal club reviewed the role of macrolide antibiotics in chronic respiratory disease. Macrolide usage was suggested from observational studies in Japan in diffuse panbroncholitis, a disorder associated with chronic respiratory infection, usually Pseudomonas aeruginosa (1. Clinical improvement was noted despite doses of antibiotics well below the minimal inhibitory concentration (MIC of the antibiotic. This suggested the antibiotic was likely working by an anti-inflammatory effect. These observations were extended to cystic fibrosis (CF where prophylactic macrolide therapy in CF patients infected with Pseudomonas has become standard therapy (2. More recently, low dose macrolide therapy has been applied to non-CF lung diseases such as chronic obstructive pulmonary disease (COPD, bronchiectasis and asthma. Time did not permit a review of all studies so a representative sample was discussed. In patients with COPD, the four randomized, placebo-controlled trials reviewed all suggested that chronic therapy with macrolide antibiotics reduced COPD exacerbations (3-5. This ...

  4. Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia

    2011-01-01

    of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product......(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations of erm(42), msr(E), and mph(E) are chromosomally encoded......(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants....

  5. A review of macrolide treatment of atherosclerosis and abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Stovring, Jette; Andersen, Paul Lehm

    2003-01-01

    of cardiovascular events among recipients of macrolide versus pencillins, macrolide treatment reduced the risk of such events after relevant adjustment. Furthermore, in two out of three minor randomized clinical trials were patients with ischaemic heart disease were randomized into antibiotic treated and placebo......, and growth of AAA. If true, it not known whether this is transient because of macrolide's non-specific anti-inflammatory effect or latent infection, or permanent because of eradicating C. pneumoniae organisms. In order to clarify this, large and long term randomized trials are needed, as well as diagnostic...... methods that can differentiate between individuals who are or are not infected with C. pneumoniae. The latter are needed in order to clarify the impact of the presence of C. pneumoniae and to avoid overconsumption of antimicrobials, which can result in serious ecological problems....

  6. Macrolide resistance can be transferred by conjugation from viridans streptococci to Streptococcus pyogenes.

    Science.gov (United States)

    Jönsson, Maria; Swedberg, Göte

    2006-08-01

    Efflux pumps encoded by mef genes are among the most common mechanisms of resistance to macrolides. These genes are often located on horizontally transferable elements such as transposons. We present data indicating conjugative transfer of the mef(E) gene from viridans streptococci to the pathogen Streptococcus pyogenes. The mef(E) gene is located on the previously described MEGA (macrolide efflux genetic assembly) element. Of 110 isolates tested, 85% of those that carried the mef(A/E) gene carried it on MEGA, and in all cases of conjugal transfer of the mef(E) gene it was carried on MEGA. It therefore appears reasonable to draw the conclusion that this element is important in the lateral transfer of macrolide resistance between streptococci.

  7. Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes.

    Science.gov (United States)

    Zhang, Yan; Tatsuno, Ichiro; Okada, Ryo; Hata, Nanako; Matsumoto, Masakado; Isaka, Masanori; Isobe, Ken-ichi; Hasegawa, Tadao

    2016-01-01

    In Japan, the number of patients with streptococcal toxic shock syndrome is reported to be increasing. mef(A) gene-positive macrolide-resistant emm1 strains are thought to possibly contribute to the rise in the frequency of STSS. Although analyses of macrolide-resistant mechanisms, including mef(A) resistance, have been performed mainly in Streptococcus pneumoniae, the role of this gene in Streptococcus pyogenes has not been completely investigated. Therefore, to the best of our knowledge, we established the first mef(A)-knockout strain using an emm1-type S. pyogenes strain, and tested its susceptibility to erythromycin, clarithromycin and azithromycin. We found that the antimicrobial susceptibilities were almost identical to those of the parental strain. Hence, we established a knockout strain for another gene, msr(D), that is located immediately downstream of mef(A). The macrolide resistances of the resulting strain significantly decreased, and were further altered when both mef(A) and msr(D) were knocked out. The introduction of the msr(D) gene into a macrolide-sensitive strain conferred more resistance than the introduction of the mef(A) gene. The erythromycin susceptibilities of knockout strains were further dissected using two additional emm4- and emm75-type S. pyogenes strains. We found almost identical results for both strains except for the mef(A) knockout emm4 type, whose susceptibility was altered, although the change was less than that for the msr(D) knockout. These results suggest that both mef(A) and msr(D) are involved in macrolide resistance in S. pyogenes, and that the msr(D) gene plays a more predominant role in macrolide resistance than mef(A).

  8. Macrolide and fluoroquinolone mediated cardiac arrhythmias: clinical considerations and comprehensive review.

    Science.gov (United States)

    Cornett, Elyse; Novitch, Matthew B; Kaye, Alan D; Pann, Chris A; Bangalore, Harish Siddaiah; Allred, Gregory; Bral, Matthew; Jhita, Preya K; Kaye, Adam M

    2017-09-01

    While there is evidence for cardiac arrhythmias associated with macrolide and fluoroquinolone antibiotics, there is still debate among health care providers as to whether this risk of arrhythmia is overstated. A joint panel of the US Food and Drug Administration suggested that macrolide and fluoroquinolone labels need much stronger warnings regarding the possible serious adverse cardiac effects associated with these antibiotics, especially since they are so widely prescribed. And while health care providers may differ on the pertinence of the cardiac risks associated with antibiotic use, they can undoubtedly minimize the cardiac effects that are associated with these antibiotics by paying attention to the cardiac risk factors and drug history associated with the patient. Relevant studies for our review were identified from a PubMed search using keywords and combined word searches involving macrolides, fluoroquinolones, and cardiac arrhythmias. We attempted to include as many recent (>2015) articles as possible. We included case reports, randomized, controlled trials, observational studies, case-control studies, systematic reviews, and retrospective studies. Underlying cardiac issues can predispose patients to harmful cardiac side effects that can be exacerbated in the presence of antibiotics. The health care provider should rule out any risk factor associated with antibiotic-induced cardiac arrhythmia in the event that a patient does need a macrolide or fluoroquinolone antibiotic. Rigorous patient evaluation and a detailed patient history, including short and long term medication use, is the likely key to reducing any risk of cardiac arrhythmias associated with macrolides and fluoroquinolones. Clinicians should be cautious when prescribing macrolide and fluoroquinolone medications to patients with risk factors that may lead to antibiotic-induced cardiac arrhythmias, including a slow heart rate and those that are taking medications to treat arrhythmias.

  9. Mutational and transcriptomic changes involved in the development of macrolide resistance in Campylobacter jejuni.

    Science.gov (United States)

    Hao, Haihong; Yuan, Zonghui; Shen, Zhangqi; Han, Jing; Sahin, Orhan; Liu, Peng; Zhang, Qijing

    2013-03-01

    Macrolide antibiotics are important for clinical treatment of infections caused by Campylobacter jejuni. Development of resistance to this class of antibiotics in Campylobacter is a complex process, and the dynamic molecular changes involved in this process remain poorly defined. Multiple lineages of macrolide-resistant mutants were selected by stepwise exposure of C. jejuni to escalating doses of erythromycin or tylosin. Mutations in target genes were determined by DNA sequencing, and the dynamic changes in the expression of antibiotic efflux transporters and the transcriptome of C. jejuni were examined by real-time reverse transcription-PCR, immunoblotting, and DNA microarray analysis. Multiple types of mutations in ribosomal proteins L4 and L22 occurred early during stepwise selection. On the contrary, the mutations in the 23S rRNA gene, mediating high resistance to macrolides, were observed only in the late-stage mutants. Upregulation of antibiotic efflux genes was observed in the intermediately resistant mutants, and the magnitude of upregulation declined with the occurrence of mutations in the 23S rRNA gene. DNA microarray analysis revealed the differential expression of 265 genes, most of which occurred in the intermediate mutant, including the upregulation of genes encoding ribosomal proteins and the downregulation of genes involved in energy metabolism and motility. These results indicate (i) that mutations in L4 and L22 along with temporal overexpression of antibiotic efflux genes precede and may facilitate the development of high-level macrolide resistance and (ii) that the development of macrolide resistance affects the pathways important for physiology and metabolism in C. jejuni, providing an explanation for the reduced fitness of macrolide-resistant Campylobacter.

  10. Relationship between copper, glycopeptide, and macrolide resistance among Enterococcus faecium strains isolated from pigs in Denmark between 1997 and 2003

    DEFF Research Database (Denmark)

    Hasman, Henrik; Aarestrup, Frank Møller

    2005-01-01

    A significant relationship between copper resistance (tcrB), glycopeptide resistance (Tn1546), and macrolide resistance [erm(B)] in Enterococcus faecium isolated from pigs was found. The tcrB gene was located closely upstream of the Tn1546 element. However, the continued use of copper sulfate has...... not been able to maintain high levels of macrolide and glycopeptide resistance....

  11. Nitrotriazole- and imidazole-based amides and sulfonamides as antitubercular agents.

    Science.gov (United States)

    Papadopoulou, Maria V; Bloomer, William D; Rosenzweig, Howard S; Arena, Alexander; Arrieta, Francisco; Rebolledo, Joseph C J; Smith, Diane K

    2014-11-01

    Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Sulfonamides as Inhibitors ofLeishmania- Potential New Treatments for Leishmaniasis.

    Science.gov (United States)

    Katinas, Jade; Epplin, Rachel; Hamaker, Christopher; Jones, Marjorie A

    2017-04-01

    Leishmaniasis is an endemic disease caused by the protozoan parasite Leishmania. Current treatments for the parasite are limited by cost, availability and drug resistance as the occurrence of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with medicinal properties which have been used to treat bacterial and parasitic disease via various pathways especially as antimetabolites for folic acid. New derivatives of sulfonamide compounds were assessed for their impact on Leishmania cell viability and potential pathways for inhibition were evaluated. Leishmania tarentolae (ATCC Strain 30143) axenic promastigote cells were grown in brain heart infusion (BHI) medium and treated with varying concentrations of the new sulfonamide compounds. Light microscopy and viability tests were used to assess the cells with and without treatment. A non-water soluble sulfonamide was determined to have 90-96% viability inhibition 24 hours after treatment with 100 µM final concentration. Because Leishmania are also autotrophs for folate precursors, the folic acid pathway was identified as a target for sulfonamide inhibition. When folic acid was added to untreated Leishmania, cell proliferation increased. A water soluble derivative of the inhibitory sulfonamide was synthesized and evaluated, resulting in less viability inhibition with a single dose (approximately 70% viability inhibition after 24 hours with 100 µM final concentration), but additive inhibition with multiple doses of the compound. However, the potential mechanism of inhibition was different between the water-soluble and non-water soluble sulfonamides. The inhibitory effects and potential pathways of inhibition indicate that these compounds may be new treatments for this disease.

  13. Macrolide resistance conferred by rRNA mutations in field isolates of Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Olsen, Anders S; Warrass, Ralf; Douthwaite, Stephen Roger

    2014-01-01

    OBJECTIVES: To determine how resistance to macrolides is conferred in field isolates of Pasteurella multocida and Mannheimia haemolytica that lack previously identified resistance determinants for rRNA methylation, efflux and macrolide-modifying enzymes. METHODS: Isolates of P. multocida and M...... by genome sequencing and primer extension on the rRNAs. RESULTS: Macrolide resistance in one M. haemolytica isolate was conferred by the 23S rRNA mutation A2058G; resistance in three P. multocida isolates were caused by mutations at the neighbouring nucleotide A2059G. In each strain, all six copies...... of the rrn operons encoded the respective mutations. There were no mutations in the ribosomal protein genes rplD or rplV, and no other macrolide resistance mechanism was evident. CONCLUSIONS: High-level macrolide resistance can arise from 23S rRNA mutations in P. multocida and M. haemolytica despite...

  14. Reversal of the in vitro susceptibility of enterococci to trimethoprim-sulfamethoxazole by folinic acid.

    OpenAIRE

    Zervos, M J; Schaberg, D R

    1985-01-01

    The in vitro susceptibilities of 21 clinical isolates of Streptococcus faecalis to trimethoprim (TMP) in combination with sulfamethoxazole (SMX) was evaluated in Mueller-Hinton broth (MHB) in the presence and absence of folinic acid as well as in urine. The mean MIC and MBC in MHB, expressed as the TMP concentration, was 0.13 and 0.32 micrograms of TMP-SMX per ml, respectively. In MHB supplemented with folinic acid, the mean MIC and MBC was 3.3 and 5.5 micrograms of TMP-SMX per ml, respective...

  15. An outbreak of trimethoprim/sulfamethoxazole-resistant Stenotrophomonas maltophilia meningitis associated with neuroendoscopy

    Directory of Open Access Journals (Sweden)

    Ching-Hsun Wang

    2014-01-01

    Full Text Available Stereotactic aspiration by neuroendoscopy for treatment of deep-seated intracranial hematomas is widely accepted because this procedure is minimally invasive and thereby reduces the probability of iatrogenic brain damage. Herein, we describe an outbreak of trimethoprim/sulfamethoxazole (TMP/SXT-resistant Stenotrophomonas maltophilia meningitis, possibly from a contaminated neuroendoscopy, and review the previous use of antimicrobial therapies for this condition without TMP/SXT. This is the first reported outbreak of TMP/SXT-resistant S. maltophilia meningitis. The discussion emphasizes the importance of adequate disinfection processes before and after endoscopic neurosurgery and the use of therapeutic options other than TMP/SXT when encountering S. maltophilia meningitis.

  16. Trimethoprim-Sulfamethoxazole-Induced Hyperkalemia in a Patient with Normal Renal Function

    Directory of Open Access Journals (Sweden)

    L. Connor Nickels

    2012-01-01

    Full Text Available The authors present a case of Trimethoprim-sulfamethoxazole-induced hyperkalemia in a patient with normal renal function. While toxicity of this drug has been reported in patients with renal insufficiency, this case highlights the toxicity associated with normal kidney function. Due to its popularity in the medical field and to the largely unrecognized effect of hyperkalemia, it is important to consider such adverse effects when prescribing TMX-SMX. One must be reminded of the possibility of the development of life-threatening hyperkalemia in relatively healthy patients.

  17. The dissolution kinetics of sulfamethoxazol, trimethoprim and oxytetracycline hydrochloride from multicomponent solid dispersion capsules ("Sulfoxytrim").

    Science.gov (United States)

    Zuń, M; Czarnecki, W

    2000-01-01

    Release profiles and dissolution kinetics of active substance, viz. sulfamethoxazol (SMO), trimethoprim (TMP), and oxytetracycline hydrochloride (OTC) from capsulated multicomponent dispersions was studied in a flow-cell apparatus at 37 degrees C by using a dissolution medium of 0.1 mol/l HCl. The results revealed that the relative dissolution efficiency (DE) and dissolution profiles of one active ingredient were affected by the presence of the two others. Vitamin C added caused the decreased the dissolution rate constants (K) and DE--values of all the active substances studied.

  18. Rhabdomyolysis due to Trimethoprim-Sulfamethoxazole Administration following a Hematopoietic Stem Cell Transplant

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn

    2015-01-01

    Full Text Available Rhabdomyolysis, a syndrome of muscle necrosis, is a life-threatening event. Here we describe the case of a patient with chronic myeloid leukemia who underwent a haploidentical stem cell transplant and subsequently developed rhabdomyolysis after beginning trimethoprim-sulfamethoxazole (TMP/SMX prophylaxis therapy. Rechallenge with TMP/SMX resulted in a repeat episode of rhabdomyolysis and confirmed the association. Withdrawal of TMP/SMX led to sustained normalization of creatine kinase levels in the patient. A high index of suspicion is necessary to identify TMP/SMX as the cause of rhabdomyolysis in immunocompromised patients.

  19. Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

    LENUS (Irish Health Repository)

    Garvey, J P

    2009-11-01

    Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.

  20. Cyclic secondary sulfonamides: unusually good inhibitors of cancer-related carbonic anhydrase enzymes.

    Science.gov (United States)

    Moeker, Janina; Peat, Thomas S; Bornaghi, Laurent F; Vullo, Daniela; Supuran, Claudiu T; Poulsen, Sally-Ann

    2014-04-24

    Carbonic anhydrase IX (CA IX) is a target for hypoxic cancer therapies, and the discovery of CA IX selective ligands is imperative for the development of these agents. Primary sulfonamides are broad specificity inhibitors of CA enzymes, while secondary sulfonamides are generally poor CA inhibitors. However, saccharin, a cyclic secondary sulfonamide, has unusually good inhibition of CA IX (Ki = 103 nM). In this study, we demonstrate that the affinity and selectivity of saccharin for CA IX can be further modulated when linked to hydrophobic or hydrophilic substituents. The hydrophilic glycoconjugate derivative (12) showed improved inhibition of CA IX (Ki = 49.5 nM) and extremely poor inhibition of the predominant off-target CAs (Ki > 50000 nM) compared to saccharin. This >1000-fold selectivity for CA IX over off-target CAs is unprecedented for classical primary sulfonamide CA inhibitors. Our study highlights the potential of cyclic secondary sulfonamides to be exploited for the discovery of potent, cancer-selective CA inhibitors.

  1. Degradation kinetics of six sulfonamides in hen eggs under simulated cooking temperatures

    Directory of Open Access Journals (Sweden)

    YING-HUA ZHANG

    2011-08-01

    Full Text Available Six sulfonamides, i.e., sulfadiazine, sulfadimethoxine, sulfamerazine, sulfamethazine, sulfamethoxazole and sulfamonomethoxine, were applied to spike whole hen eggs at 0.1 mg kg-1 eggs. The spiked hen eggs were heated at 80 and 100 °C to investigate the degradation kinetics of the sulfonamides under simu­lated cooking conditions. The sulfonamides added were extracted twice from the spiked eggs with dichloromethane by an ultrasonic-assisted extraction, and analyzed by a HPLC method after purification. The first-order rate constants and half-life times of the sulfonamides were calculated, and the corresponding apparent activation energy of their degradation was also obtained by applica­tion of the Arrhenius equation. The results indicated that all six sulfonamides degraded faster at the higher heating temperature, with first-order rate constants ranging from 0.0056 to 0.0108 min-1 at 80 °C and from 0.0147 to 0.0394 min-1 at 100 °C. The apparent activation energies for the degradation of the sulfon­amides were estimated to be in the range 30.9 to 77.5 kJ mol-1. Sulfadiazine and sulfadimethoxine had the shortest and longest half-life time, respectively, and were the most instable and stable.

  2. Interception of amide ylides with sulfonamides: synthesis of (E)-N-sulfonyl amidines catalyzed by Zn(OTf)2.

    Science.gov (United States)

    Chen, Jijun; Long, Wenhao; Fang, Shangwen; Yang, Yonggang; Wan, Xiaobing

    2017-12-12

    Through the interception of amide ylides with sulfonamides, we herein report the first general example of an intermolecular condensation reaction between sulfonamides and amides. Beyond formamides, this approach was successfully applied to a variety of lactams and linear amides, giving rise to a broad array of (E)-N-sulfonyl amidines.

  3. Extraction procedure for sulfachloropyridazine in porcine tissues and detection in a sulfonamide-specific enzyme-linked immunosorbent assay (ELISA)

    NARCIS (Netherlands)

    Cliquet, P.; Cox, E.; Haasnoot, W.; Schacht, B.; Goddeeris, B.M.

    2003-01-01

    Sulfonamide-specific polyclonal rabbit antibodies were obtained after immunization with a sulfathiazole derivative (N1-[4-(carboxymethyl)-2-thiazolyl]sulfanilamide = TS) coupled to keyhole lympet hemocyanin. Using these antibodies, two sulfonamide-specific enzyme-linked immunosorbent assays (ELISAs)

  4. Dominance of multidrug resistant CC271 clones in macrolide-resistant streptococcus pneumoniae in Arizona

    Directory of Open Access Journals (Sweden)

    Bowers Jolene R

    2012-01-01

    Full Text Available Abstract Background Rates of resistance to macrolide antibiotics in Streptococcus pneumoniae are rising around the world due to the spread of mobile genetic elements harboring mef(E and erm(B genes and post-vaccine clonal expansion of strains that carry them. Results Characterization of 592 clinical isolates collected in Arizona over a 10 year period shows 23.6% are macrolide resistant. The largest portion of the macrolide-resistant population, 52%, is dual mef(E/erm(B-positive. All dual-positive isolates are multidrug-resistant clonal lineages of Taiwan19F-14, mostly multilocus sequence type 320, carrying the recently described transposon Tn2010. The remainder of the macrolide resistant S. pneumoniae collection includes 31% mef(E-positive, and 9% erm(B-positive strains. Conclusions The dual-positive, multidrug-resistant S. pneumoniae clones have likely expanded by switching to non-vaccine serotypes after the heptavalent pneumococcal conjugate vaccine release, and their success limits therapy options. This upsurge could have a considerable clinical impact in Arizona.

  5. Kinetics of drug-ribosome interactions defines the cidality of macrolide antibiotics.

    Science.gov (United States)

    Svetlov, Maxim S; Vázquez-Laslop, Nora; Mankin, Alexander S

    2017-12-26

    Antibiotics can cause dormancy (bacteriostasis) or induce death (cidality) of the targeted bacteria. The bactericidal capacity is one of the most important properties of antibacterial agents. However, the understanding of the fundamental differences in the mode of action of bacteriostatic or bactericidal antibiotics, especially those belonging to the same chemical class, is very rudimentary. Here, by examining the activity and binding properties of chemically distinct macrolide inhibitors of translation, we have identified a key difference in their interaction with the ribosome, which correlates with their ability to cause cell death. While bacteriostatic and bactericidal macrolides bind in the nascent peptide exit tunnel of the large ribosomal subunit with comparable affinities, the bactericidal antibiotics dissociate from the ribosome with significantly slower rates. The sluggish dissociation of bactericidal macrolides correlates with the presence in their structure of an extended alkyl-aryl side chain, which establishes idiosyncratic interactions with the ribosomal RNA. Mutations or chemical alterations of the rRNA nucleotides in the drug binding site can protect cells from macrolide-induced killing, even with inhibitor concentrations that significantly exceed those required for cell growth arrest. We propose that the increased translation downtime due to slow dissociation of the antibiotic may damage cells beyond the point where growth can be reinitiated upon the removal of the drug due to depletion of critical components of the gene-expression pathway.

  6. Molecular epidemiology, antimicrobial susceptibility, and characterization of macrolide-resistant Streptococcus pyogenes in Japan.

    Science.gov (United States)

    Tanaka, Yuhei; Gotoh, Kenji; Teramachi, Mariko; Ishimoto, Kazuhisa; Tsumura, Naoki; Shindou, Shizuo; Yamashita, Yushiro

    2016-11-01

    Here we report the molecular epidemiology of macrolide-resistant Streptococcus pyogenes (group A streptococci, GAS) isolated from children with pharyngotonsillitis between 2011 and 2013 in Japan. In 299 isolates, 124 (41.5%) isolates were macrolide-resistant. We characterized the isolates by emm typing, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Of 299 isolates, 124 (41.5%) were macrolide-resistant isolates, 76 (61.3%) possessed mefA and 46 (37.1%) possessed ermB. All 76 isolates with mefA possessed msrD. There were no isolates possessed ermTR in this study. Eight emm/MLST types were observed. The predominant type was emm1/ST28 (57 isolates, 46.0%), which possessed the mefA/msrD complex, presenting as the M phenotype. The second most predominant type was emm12/ST467, which possessed ermB, presenting as the cMLS B phenotype. Of the cMLS B phenotype isolates, types emm28/ST52 and emm12/ST36 had multiple genetic backgrounds. We found high proportions of macrolide-resistant GAS in the southwestern areas of Japan. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Evaluation of macrolides for possible use against multidrug-resistant Mycobacterium tuberculosis

    NARCIS (Netherlands)

    van der Paardt, Anne-Fleur; Wilffert, Bob; Akkerman, Onno W.; de Lange, Wiel C. M.; van Soolingen, Dick; Sinha, Bhanu; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    Multidrug-resistant tuberculosis (MDR-TB) is a major global health problem. The loss of susceptibility to an increasing number of drugs behoves us to consider the evaluation of non-traditional anti-tuberculosis drugs. Clarithromycin, a macrolide antibiotic, is defined as a group 5 anti-tuberculosis

  8. Macrolide-Resistance Selection in Tibetan Pigs with a High Load of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Qiu, Gang; Rui, Yapei; Zhang, Jialu; Zhang, Lihong; Huang, Shucheng; Wu, Qingxia; Li, Kun; Han, Zhaoqing; Liu, Suozhu; Li, Jiakui

    2017-12-22

    Currently, tylosin tartrate is the first-line treatment for Mycoplasma hyopneumoniae infections in China. However, the efficacy of tylosin tartrate and resistance to this treatment in M. hyopneumoniae infections of Tibetan pigs are unknown. In this study, we examined the prevalence of M. hyopneumoniae infection in Tibetan pigs at three intensive farms in Tibet, China. In addition, we investigated the efficacy of tylosin tartrate treatment for porcine enzootic pneumonia by monitoring M. hyopneumoniae DNA eradication dynamics and macrolide resistance (MR). Eighty-two of 450 (18.2%) Tibetan pigs tested positive for only M. hyopneumoniae, and most of these animals (85.1%) had symptoms and signs of pneumonia. The elimination of M. hyopneumoniae DNA was substantially faster in Tibetan pigs with a lower pretreatment M. hyopneumoniae load, and the total eradication rate was 97.4% (75/77). Two Tibetan pigs tested positive for M. hyopneumoniae that contained macrolide resistance-determining mutations in the 23S rRNA gene. Our results indicate that the pretreatment M. hyopneumoniae load may be an effective predictor of macrolide treatment efficacy (and possibly that of other antimicrobial agents) and MR. Moreover, our results suggest that danofloxacin mesylate can be used as an alternative drug for the treatment of macrolide-resistant M. hyopneumoniae infection acquired during intensive farming.

  9. New polyene macrolide family produced by submerged culture of Streptomyces durmitorensis

    Czech Academy of Sciences Publication Activity Database

    Stodůlková, Eva; Kuzma, Marek; Hench, I. B.; Černý, J.; Králová, Jarmila; Novák, Petr; Chudíčková, Milada; Savic, M.; Djokic, L.; Vasiljevic, B.; Flieger, Miroslav

    2011-01-01

    Roč. 64, č. 11 (2011), s. 717-722 ISSN 0021-8820 R&D Projects: GA MŠk 2B08064 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50520514 Keywords : apoptosis * FTMS * polyene macrolide Subject RIV: EE - Microbiology, Virology Impact factor: 1.651, year: 2011

  10. Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia.

    Science.gov (United States)

    Williams, Derek J; Edwards, Kathryn M; Self, Wesley H; Zhu, Yuwei; Arnold, Sandra R; McCullers, Jonathan A; Ampofo, Krow; Pavia, Andrew T; Anderson, Evan J; Hicks, Lauri A; Bramley, Anna M; Jain, Seema; Grijalva, Carlos G

    2017-12-01

    β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches. To compare the effectiveness of β-lactam monotherapy vs β-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia. We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children's hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017. We defined the referent as β-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients' length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up. Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the

  11. Modeling of the solubility of Naproxen and Trimethoprim in different solvents at different temperature

    Directory of Open Access Journals (Sweden)

    Moudjari Y.

    2013-07-01

    Full Text Available The study concerns the prediction of the solubility of pharmaceutical compounds such as Trimethoprim and Naproxen in various solvents like Methanol, Ethanol, 1-Propanol, 2-Propanol, 1-Butanol and 2-Butanol for the first solute and Chloroform, Octanol and Cyclohexane, for the second one. The solubility prediction was performed using thermodynamic models like the UNIFAC, which is a group contribution method, and the semi-predictive model like NRTL. The required interaction parameters for the NRTL are not available and are calculated by optimizing an objective function involving experimental data reported in the literature for the considered systems. Also the obtained results by means of the UNIFAC model for Naproxen showed deviations from the experimental data and therefore new molecular decompositions to generate new groups are proposed and the corresponding interaction parameters are calculated. The influence of the molecular structure on the behavior of the mixture is also discussed. On the other hand a new group representing the Aromatic Nitrogen (AN present in Trimethoprim is introduced and new interaction parameters concerning these groups are calculated. Finally it may be concluded that the NRTL model led to the best results for the solubility prediction for pharmaceutical compounds.

  12. Antibiotics degradation in soil: A case of clindamycin, trimethoprim, sulfamethoxazole and their transformation products.

    Science.gov (United States)

    Koba, Olga; Golovko, Oksana; Kodešová, Radka; Fér, Miroslav; Grabic, Roman

    2017-01-01

    Twelve different soil types that represent the soil compartments of the Czech Republic were fortified with three antibiotics (clindamycin (CLI), sulfamethoxazole (SUL), and trimethoprim (TRI)) to investigate their fate. Five metabolites (clindamycin sulfoxide (CSO), hydroxy clindamycin sulfoxide (HCSO), S-(SDC) and N-demethyl clindamycin (NDC), N 4 -acetyl sulfamethoxazole (N 4 AS), and hydroxy trimethoprim (HTR)) were detected and identified using HPLC/HRMS and HRPS in the soil matrix in this study. The identities of CSO and N 4 AS were confirmed using commercially available reference standards. The parent compounds degraded in all soils. Almost all of the metabolites have been shown to be persistent in soils, with the exception of N 4 AS, which was formed and degraded completely within 23 days of exposure. The rate of degradation mainly depended on the soil properties. The PCA results showed a high dependence between the soil type and behaviour of the pharmaceutical metabolites. The mentioned metabolites can be formed in soils, and the most persistent ones may be transported to the ground water and environmental water bodies. Because no information on the effects of those metabolites on living organism are available, more studies should be performed in the future to predict the risk to the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations.

    Science.gov (United States)

    Ivanova, Jekaterīna; Balode, Agnese; Žalubovskis, Raivis; Leitans, Janis; Kazaks, Andris; Vullo, Daniela; Tars, Kaspars; Supuran, Claudiu T

    2017-02-01

    A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (K I s in the range of 683-4250nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar-nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Macrolide resistance conferred by rRNA mutations in field isolates of Mannheimia haemolytica and Pasteurella multocida.

    Science.gov (United States)

    Olsen, Anders S; Warrass, Ralf; Douthwaite, Stephen

    2015-02-01

    To determine how resistance to macrolides is conferred in field isolates of Pasteurella multocida and Mannheimia haemolytica that lack previously identified resistance determinants for rRNA methylation, efflux and macrolide-modifying enzymes. Isolates of P. multocida and M. haemolytica identified as being highly resistant (MICs >64 mg/L) to the macrolides erythromycin, gamithromycin, tilmicosin, tildipirosin and tulathromycin were screened by multiplex PCR for the previously identified resistance genes erm(42), msr(E) and mph(E). Strains lacking these determinants were analysed by genome sequencing and primer extension on the rRNAs. Macrolide resistance in one M. haemolytica isolate was conferred by the 23S rRNA mutation A2058G; resistance in three P. multocida isolates were caused by mutations at the neighbouring nucleotide A2059G. In each strain, all six copies of the rrn operons encoded the respective mutations. There were no mutations in the ribosomal protein genes rplD or rplV, and no other macrolide resistance mechanism was evident. High-level macrolide resistance can arise from 23S rRNA mutations in P. multocida and M. haemolytica despite their multiple copies of rrn. Selective pressures from exposure to different macrolide or lincosamide drugs presumably resulted in consolidation of either the A2058G or the A2059G mutation. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Nanoemulsions of sulfonamide carbonic anhydrase inhibitors strongly inhibit the growth of Trypanosoma cruzi.

    Science.gov (United States)

    Vermelho, Alane Beatriz; da Silva Cardoso, Verônica; Ricci Junior, Eduardo; Dos Santos, Elisabete Pereira; Supuran, Claudiu T

    2018-12-01

    Sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors targeting the α-class enzyme from the protozoan pathogen Trypanosoma cruzi, responsible of Chagas disease, were recently reported. Although many such derivatives showed low nanomolar activity in vitro, they were inefficient anti-T. cruzi agents in vivo. Here, we show that by formulating such sulfonamides as nanoemulsions in clove (Eugenia caryophyllus) oil, highly efficient anti-protozoan effects are observed against two different strains of T. cruzi. These effects are probably due to an enhanced permeation of the enzyme inhibitor through the nanoemulsion formulation, interfering in this way with the life cycle of the pathogen either by inhibiting pH regulation or carboxylating reactions in which bicarbonate/CO 2 are involved. This type of formulation of sulfonamides with T. cruzi CA inhibitory effects may lead to novel therapeutic approaches against this orphan disease.

  16. RESIDUES OF TETRACYCLINES, SULFONAMIDES AND TYLOSIN IN JAR HONEY FROM LATIUM REGION DURING 2005-2007

    Directory of Open Access Journals (Sweden)

    P. Pulcini

    2008-12-01

    Full Text Available During 3 years (2005-2007, the IZSLT, and the C.R.A. (ex Sezione di Apicoltura dell’Istituto Sperimentale per la Zoologia Agraria – sede di Roma, analized 165 samples of jar honey, from Latium Region, for melissopalinological, sensorial, chemical and physical analysis. The screening test for tetracyclines and tylosin were performed, respectively, with the Tetrasensor Honey kit and the ELISA kit for tylosin. HPLC-ESI-MSMS was used for sulfonamides and for all the samples that resulted positives to the screenig test for tetracyclines and tylosin. These the results: 49% of samples presented not in conformities; 18 samples (11% of the total were positives for tetracyclines; 15 - samples (9% positives for sulfonamides; 6 samples (4% positives for both tetracyclines and sulfonamides; 0 samples resulted positives for tylosin.

  17. Committee Opinion No. 717 Summary: Sulfonamides, Nitrofurantoin, and Risk of Birth Defects.

    Science.gov (United States)

    2017-09-01

    The evidence regarding an association between the nitrofuran and sulfonamide classes of antibiotics and birth defects is mixed. As with all patients, antibiotics should be prescribed for pregnant women only for appropriate indications and for the shortest effective duration. During the second and third trimesters, sulfonamides and nitrofurantoins may continue to be used as first-line agents for the treatment and prevention of urinary tract infections and other infections caused by susceptible organisms. Prescribing sulfonamides or nitrofurantoin in the first trimester is still considered appropriate when no other suitable alternative antibiotics are available. Pregnant women should not be denied appropriate treatment for infections because untreated infections can commonly lead to serious maternal and fetal complications.

  18. Committee Opinion No. 717: Sulfonamides, Nitrofurantoin, and Risk of Birth Defects.

    Science.gov (United States)

    2017-09-01

    The evidence regarding an association between the nitrofuran and sulfonamide classes of antibiotics and birth defects is mixed. As with all patients, antibiotics should be prescribed for pregnant women only for appropriate indications and for the shortest effective duration. During the second and third trimesters, sulfonamides and nitrofurantoins may continue to be used as first-line agents for the treatment and prevention of urinary tract infections and other infections caused by susceptible organisms. Prescribing sulfonamides or nitrofurantoin in the first trimester is still considered appropriate when no other suitable alternative antibiotics are available. Pregnant women should not be denied appropriate treatment for infections because untreated infections can commonly lead to serious maternal and fetal complications.

  19. Synthesis and biological evaluation of novel quinazoline-sulfonamides as anti-cancer agents.

    Science.gov (United States)

    Poudapally, Suresh; Battu, Shankar; Velatooru, Loka Reddy; Bethu, Murali Satyanarayana; Janapala, Venkateswara Rao; Sharma, Somesh; Sen, Subhabrata; Pottabathini, Narender; Iska, Vijaya Bhaskara Reddy; Katangoor, Vidya

    2017-05-01

    A robust economic approach to N-(quinazoline-4-yl)sulfonamides was developed and synthesized different aryl, hetero aryl, alkyl and cyclopropyl sulfonamides in excellent yields. All the compounds were evaluated for cytotoxic affinity to SKOV3, DU145, THP1, U937, and COLO205 cell lines. Interesting to find that the bulkiness of substituent at C-2 position of quinazoline forces the molecule to flip around in order to bind in the active site, when compared to the binding preference of previously known quinazoline compounds. Among the 21 compounds synthesized 2b, 2d, 2e, 2h, 2i, 3c, 3d, 3f, 3g and 3h found to be active on all the cell lines tested with IC 50 values <10µg/mL. Performed docking simulations to understand the binding preference of various C-2 substituted quinazoline sulfonamides. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry

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    Gerchman Irena

    2011-08-01

    Full Text Available Abstract The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18 of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS, detected 13 molecular types (I-XIII. Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01 and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides.

  1. Prevalence of Genotypes That Determine Resistance of Staphylococci to Macrolides and Lincosamides in Serbia.

    Science.gov (United States)

    Mišić, Milena; Čukić, Jelena; Vidanović, Dejan; Šekler, Milanko; Matić, Sanja; Vukašinović, Mihailo; Baskić, Dejan

    2017-01-01

    Macrolides, lincosamides, and streptogramins (MLS) resistance genes are responsible for resistance to these antibiotics in Staphylococcus infections. The purpose of the study was to analyze the distribution of the MLS resistance genes in community- and hospital-acquired Staphylococcus isolates. The MLS resistance phenotypes [constitutive resistance to macrolide-lincosamide-streptogramin B (cMLSb), inducible resistance to macrolide-lincosamide-streptogramin B (iMLSb), resistance to macrolide/macrolide-streptogramin B (M/MSb), and resistance to lincosamide-streptogramin A/streptogramin B (LSa/b)] were determined by double-disc diffusion method. The presence of the MLS resistance genes ( erm A, erm B, erm C, msr A/B, lnu A, lnu B, and lsa A) were determined by end-point polymerase chain reaction in 179 isolates of staphylococci collected during 1-year period at the Center for Microbiology of Public Health Institute in Vranje. The most frequent MLS phenotype among staphylococcal isolates, both community-acquired and hospital-acquired, was iMLSb (33.4%). The second most frequent was M/MSb (17.6%) with statistically significantly higher number of hospital-acquired staphylococcal isolates ( p  staphylococci (MRCNS) (90.9%) isolates with cMLSB phenotype. The msr A/B gene and M/MSb phenotype were statistically significantly higher in hospital-acquired than community-acquired staphylococci strains ( p  staphylococci harboring the rest of MLS resistance genes acquired in community and hospital settings ( p  > 0.05). The prevalence of iMLSb phenotypes may change over time, so it is necessary to perform periodic survey of MLS resistance phenotypes, particularly where the D-test is not performed routinely.

  2. Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

    Directory of Open Access Journals (Sweden)

    Markus Menke

    2016-12-01

    Full Text Available The contents of the gular glands of the male African reed frog Hyperolius cinnamomeoventris consist of a mixture of aliphatic macrolides and sesquiterpenes. While the known macrolide gephyromantolide A was readily identified, the structure of another major component was suggested to be a tetradecen-13-olide. The synthesis of the two candidate compounds (Z-5- and (Z-9-tetradecen-13-olide revealed the former to be the naturally occurring compound. The synthesis used ring-closing metathesis as key step. While the Hoveyda–Grubbs catalyst furnished a broad range of isomeric products, the (Z-selective Grubbs catalyst lead to pure (Z-products. Analysis by chiral GC revealed the natural frog compound to be (5Z,13S-5-tetradecen-13-olide (1. This compound is also present in the secretion of other hyperoliid frogs as well as in femoral glands of male mantellid frogs such as Spinomantis aglavei. The mass spectra of the synthesized macrolides as well as their rearranged isomers obtained during ring-closing metathesis showed that it is possible to assign the location of the double bond in an unsaturated macrolide on the basis of its EI mass spectrum. The occurrence of characteristic ions can be explained by the fragmentation pathway proposed in the article. In contrast, the localization of a double bond in many aliphatic open-chain compounds like alkenes, alcohols or acetates, important structural classes of pheromones, is usually not possible from an EI mass spectrum. In the article, we present the synthesis and for the first time elucidate the structure of macrolides from the frog family Hyperoliidae.

  3. Effect of subtherapeutic vs therapeutic administration of macrolides on antimicrobial resistance in Mannheimia haemolytica and enterococci isolated from beef cattle

    Directory of Open Access Journals (Sweden)

    Rahat eZaheer

    2013-05-01

    Full Text Available Macrolides are the first-line treatment against bovine respiratory disease, and are also used to treat infections in humans. The macrolide, tylosin phosphate, is often included in the diet of cattle as a preventative for liver abscesses in many regions of the world outside of Europe. This study investigated the effects of administering macrolides to beef cattle either systemically through a single subcutaneous injection (therapeutic or continuously in-feed (subtherapeutic, on the prevalence and antimicrobial resistance of Mannheimia haemolytica and Enterococcus spp. isolated from the nasopharynx and faeces, respectively. Nasopharyngeal and faecal samples were collected weekly over 28 days from untreated beef steers and from steers injected once with tilmicosin or tulathromycin or continuously fed tylosin phosphate at dosages recommended by manufacturers. Tilmicosin and tulathromycin were effective in lowering (P < 0.05 the prevalence of M. haemolytica, whereas subtherpeutic tylosin had no effect. M. haemolytica isolated from control- and macrolide-treated animals were susceptible to macrolides as well as to other antibiotics. Major bacteria co-isolated with M. haemolytica included Pasteurella multocida, Staphylococcus spp., Acinetobacter spp., E. coli and Bacillus spp. With the exception of M. haemolytica and P. multocida, erythromycin resistance was frequently found in other isolated species. Both methods of macrolide administration increased (P < 0.05 the levels erythromycin-resistance enterococci in faeces. Development of resistance to injectable macrolides in bacteria isolated from the nasopharynx was species dependent. Therapeutic administration of tilmicosin and tularthromycin selected for macrolide resistant bacteria within both the respiratory and intestinal tract, whereas suptherapeutic administration of tylosin only selected for macrolide resistance in enteric bacteria.

  4. Identification and dynamic modeling of biomarkers for bacterial uptake and effect of sulfonamide antimicrobials

    International Nuclear Information System (INIS)

    Richter, Merle K.; Focks, Andreas; Siegfried, Barbara; Rentsch, Daniel; Krauss, Martin; Schwarzenbach, René P.; Hollender, Juliane

    2013-01-01

    The effects of sulfathiazole (STA) on Escherichia coli with glucose as a growth substrate was investigated to elucidate the effect-based reaction of sulfonamides in bacteria and to identify biomarkers for bacterial uptake and effect. The predominant metabolite was identified as pterine-sulfathiazole by LC-high resolution mass spectrometry. The formation of pterine-sulfathiazole per cell was constant and independent of the extracellular STA concentrations, as they exceeded the modeled half-saturation concentration K M S of 0.011 μmol L −1 . The concentration of the dihydrofolic acid precursor para-aminobenzoic acid (pABA) increased with growth and with concentrations of the competitor STA. This increase was counteracted for higher STA concentrations by growth inhibition as verified by model simulation of pABA dynamics. The EC value for the inhibition of pABA increase was 6.9 ± 0.7 μmol L −1 STA, which is similar to that calculated from optical density dynamics indicating that pABA is a direct biomarker for the SA effect. - Highlights: ► Elucidation of the effect-based reaction of sulfonamides in bacteria. ► Identification of a biomarker for uptake and effect-based reaction of sulfonamides. ► Investigation of a biomarker for the bacterial growth inhibition by sulfonamides. ► Quantitative mechanistic modeling of biomarker dynamics using enzyme kinetics. ► Mechanistic quantitative linking of sulfonamide concentrations and effects. - Identification of specific biomarkers for the uptake and effect-based reaction of sulfonamides in bacteria and resulting growth inhibition.

  5. Detection of Class 1 and 2 Integrons, β-Lactamase Genes and Molecular Characterization of Sulfonamide Resistance in Escherichia coli Isolates Recovered from Poultry in China

    Directory of Open Access Journals (Sweden)

    Jam Kashif§, Rehana Buriro§, Javed Memon, Muhammad Yaqoob, Jamila Soomro§, Diao Dongxue, Huang Jinhu and Wang Liping*

    2013-07-01

    Full Text Available This study aimed to detect integrons, β-lactamase genes and to characterize sulfonamide resistant E. coli isolates recovered from poultry. All the isolates (n=38 were investigated for the presence of integrons, Sul1, Sul2, Sul3 genes by PCR. Class 1 and class 2 integron were present in 79 and 16%, respectively. Additional resistance gene cassette embedded in class 1 and 2 integrons was aadA1, aadA5, dfrA17 and aadA22, dfrA, respectively. Sul1 and Sul2 genes were detected in 42.1 and 60.5% isolates, respectively. Both the Sul1 and Sul2 were present in 23% isolates. However, Sul3 gene was not present. Co-existence of Sul1 and Sul2 with class 1 integrons was found in 28.9 and 60.5% of class 1 integron positive isolates, respectively. Whereas, a less percentage of isolates showed a low level of resistance to β-lactams and no blaCTX-M, blaSHV and blaTEM was found. The MIC results showed resistance to sulfadiazine and sulfamethoxazole-trimethoprim in 88 and 84% isolates, resistance to penicillin, ampicillin, amoxicillin was 52, 52 and 44%, respectively. Chloramphenicol, florfenicol, tetracycline and gentamycin resistance was found in 51, 5, 42 and 67% isolates, respectively. This study revealed high frequency of class 1 integrons, Sul genes among poultry E. coli isolates, therefore further spread of Sul genes and integrons is predictable.

  6. Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease.

    Science.gov (United States)

    Schulte, T; Mattern, R; Berger, K; Szymanski, S; Klotz, P; Kraus, P H; Przuntek, H; Schöls, L

    2001-09-01

    To evaluate the efficiency of a combination of trimethoprim and sulfamethoxazole in patients with spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). Placebo-controlled, double-blind crossover trial in 22 patients with genetically confirmed SCA3/MJD. Study phases of 6 months were separated by a washout period of 4 weeks. Dosages were a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim, 80 mg, and sulfamethoxazole, 400 mg, twice daily for 5.5 months. Outpatient department of the Neurological Clinic, Ruhr-University, Bochum, Germany. Ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing. Effects on the visual system were studied using the achromatic Vision Contrast Test System and the Farnsworth-Munsell 100-hue test for color discrimination. Physical and mental health were documented using the Medical Outcomes Study 36-Item Short-Form Health Survey. Subgroup analyses assessed the influence of age, sex, age at onset, duration of the disease, phenotype, and CAG repeat length on test performance. Twenty of 22 patients completed the study. Dropouts were due to a rash (placebo phase) and an attempted suicide in a family conflict. Trimethoprim-sulfamethoxazole therapy had no significant effect in SCA3/MJD patients in the short-term analysis (2 weeks) or in the long-term interval (6 months). In contrast to previous reports that studied smaller groups of patients, treatment with trimethoprim-sulfamethoxazole did not improve the diverse and complex movement disorders caused by SCA3/MJD. Trimethoprim-sulfamethoxazole had no effect on the visual system and cannot be recommended as a continuous treatment for SCA3/MJD patients.

  7. Determination of sulfonamides in meat by liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dal Ho; Choi, Jong Oh; Kim, Jin Seog [Korea Research Institute of Standards and Science, Daejon (Korea, Republic of); Lee, Dai Woon [Yonsei Univ., Seoul (Korea, Republic of)

    2002-11-01

    Liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) has been used for the determination of sulfonamides in meat. Five typical sulfonamides were selected as target compounds, and beef meat was selected as a matrix sample. As internal standards, sulfapyridine and isotope labeled sulfamethazine ({sup 13}C{sub 6}-SMZ) were used. Compared to the results of recent reports, our results have shown improved precision to a RSD of 1.8% for the determination of sulfamethazine spiked with 75 ng/g level in meat.

  8. Synthesis and bioactivity of several new hetaryl sulfonamides.

    Science.gov (United States)

    Taslimi, Parham; Sujayev, Afsun; Mamedova, Sevgi; Kalın, Pınar; Gulçin, İlhami; Sadeghian, Nastaran; Beydemir, Sukru; Kufrevioglu, O Irfan; Alwasel, Saleh H; Farzaliyev, Vagif; Mamedov, Sabir

    2017-12-01

    1-(4-Methylsulfonyl)-2-thione-4-aryl-5-Z-6-methyl and oxyalkyl-imidazoles were synthesized from different tetrahydropyrimidinethiones and aryl sulfonyl chloride. These compunds were tested for metal chelating effects and to determine the phrase in which inhibition occured between two physiologically pertinent compunds and carbonic anhydrase (CA) isozymes I and II (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). AChE was detected in high concentrations in the brain and red blood cells. BChE is another enzymes that is abundant available in the liver and released into the blood in a soluble form. Newly synthesized hetaryl sulfonamides exhibited impressive inhibition profiles with Ki values in the range of 1.42-6.58 nM against hCA I, 1.72-7.41 nM against hCA II, 0.20-1.14 nM against AChE and 1.55-5.92 nM against BChE. Moreover, acetazolamide showed Ki values of 43.69 ± 6.44 nM against hCA I and 31.67 ± 8.39 nM against hCA II. Additionally, tacrine showed Ki values of 25.75 ± 3.39 nM and 37.82 ± 2.08 against AChE and BChE, respectively.

  9. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... resistance in Campylobacter and track resistance trends in human clinical isolates in relation to use of these agents in food animals. Susceptibility data suggest that erythromycin and other macrolides should remain the drugs of choice in most regions, with systematic surveillance and central measures...

  10. Emergence of Plasmid-Borne dfrA14 Trimethoprim Resistance Gene in Shigella sonnei

    Directory of Open Access Journals (Sweden)

    ALFONSO MIRANDA

    2016-07-01

    Full Text Available The most common mechanism of trimethoprim (TMP-resistance is the acquisition of dihydrofolate reductase enzyme resistant to this drug. Previous molecular characterization of TMP-genes resistance in Chilean isolates of S. sonnei searching for dfrA1 and dfrA8, showed solely the presence of dfrA8 (formerly dhfrIIIc. However, these genetic markers were absent in S. sonnei strains further isolated during an outbreak in 2009. To identify the TMP-resistance gene in these strains, a genomic DNA library from a TMP-resistant (TMPR S. sonnei representative strain for the outbreak was used to clone, select and identify a TMP-resistance marker. The TMPR clone was sequenced by primer walking, identifying the presence of the dfrA14 gene in the sul2-strA’-dfrA14-‘strA-strB gene arrangement, harbored in a native 6,779-bp plasmid. The same plasmid was isolated by transforming with a ~4.2 MDa plasmid extracted from several TMPR S. sonnei strains into E. coli. This plasmid, named pABC-3, was present only in dfrA14-positive strains and was homologous to a previously described pCERC-1, but different due to the absence of an 11-bp repetitive unit. The distribution of dfrA1, dfrA8 and dfrA14 TMP-resistance genes was determined in 126 TMPR S. sonnei isolates. Most of the strains (96 % carried only one of the three TMP-resistance genes assessed. Thus, all strains obtained during the 2009-outbreak harbored only dfrA14, whereas, dfrA8 was the most abundant gene marker before outbreak and, after the outbreak dfrA1 seems have appeared in circulating strains. According to PFGE, dfrA14-positive strains were clustered in a genetically related group including some dfrA1- and dfrA8-positive strains; meanwhile other genetic group included most of the dfrA8-positive strains. This distribution also correlated with the isolation period, showing a dynamics of trimethoprim genetic markers prevalent in Chilean S. sonnei strains. To our knowledge, dfrA14 gene associated to a small

  11. Trimethoprim-sulfamethoxazole-induced Steven Johnson syndrome in an HIV-infected patient.

    Science.gov (United States)

    Taqi, Syed Ahmed; Zaki, Syed Ahmed; Nilofer, Angadi Rajasab; Sami, Lateef Begum

    2012-01-01

    Trimethoprim-sulfamethoxazole (TMP/SMX) is a widely prescribed antimicrobial for the management of several uncomplicated infections. It is commonly used for the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in the HIV-infected population. The adverse reaction to TMP/SMX is more frequent and severe in HIV-infected patients as compared to the general population. Here, we report a case of Stevens-Johnson syndrome (SJS) secondary to TMP/SMX. The patient had a generalized cutaneous reaction with involvement of the eyes, oral cavity, and genitals. He had elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme. TMP/SMX therapy was stopped and supportive treatment was started. His condition improved after eight days of stopping TMP/SMX therapy.

  12. Single-day trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis pneumonia in children with cancer.

    Science.gov (United States)

    Caselli, Désirée; Petris, Maria Grazia; Rondelli, Roberto; Carraro, Francesca; Colombini, Antonella; Muggeo, Paola; Ziino, Ottavio; Melchionda, Fraia; Russo, Giovanna; Pierani, Paolo; Soncini, Elena; DeSantis, Raffaella; Zanazzo, Giulio; Barone, Angelica; Cesaro, Simone; Cellini, Monica; Mura, Rossella; Milano, Giuseppe M; Meazza, Cristina; Cicalese, Maria P; Tropia, Serena; De Masi, Salvatore; Castagnola, Elio; Aricò, Maurizio

    2014-02-01

    To determine whether a simplified, 1-day/week regimen of trimethoprim/sulfamethoxazole is sufficient to prevent Pneumocystis (jirovecii [carinii]) pneumonia (PCP). Current recommended regimens for prophylaxis against PCP range from daily administration to 3 consecutive days per week dosing. A prospective survey of the regimens adopted for the PCP prophylaxis in all patients treated for childhood cancer at pediatric hematology-oncology centers of the Associazione Italiana Ematologia Oncologia Pediatrica. The 20 centers participating in the study reported a total of 2466 patients, including 1093 with solid tumor and 1373 with leukemia/lymphoma (or primary immunodeficiency; n = 2). Of these patients, 1371 (55.6%) received the 3-day/week prophylaxis regimen, 406 (16.5%) received the 2-day/week regimen, and 689 (27.9%), including 439 with leukemia/lymphoma, received the 1-day/week regimen. Overall, only 2 cases of PCP (0.08%) were reported, both in the 2-day/week group. By intention to treat, the cumulative incidence of PCP at 3 years was 0.09% overall (95% CI, 0.00-0.40%) and 0.51% for the 2-day/week group (95% CI, 0.10%-2.00%). Remarkably, both patients who failed had withdrawn from prophylaxis. A single-day course of prophylaxis with trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in children with cancer undergoing intensive chemotherapy regimens. This simplified strategy might have implications for the emerging need for PCP prophylaxis in other patients subjected to the increased use of biological and nonbiological agents that induce higher levels of immune suppression, such as those with rheumatic diseases. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  13. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  14. Macrolide antibiotic-mediated downregulation of MexAB-OprM efflux pump expression in Pseudomonas aeruginosa.

    Science.gov (United States)

    Sugimura, Makoto; Maseda, Hideaki; Hanaki, Hideaki; Nakae, Taiji

    2008-11-01

    Macrolide antibiotics modulate the quorum-sensing system of Pseudomonas aeruginosa. We tested the effect of macrolide antibiotics on the cell density-dependent expression of the MexAB-OprM efflux pump and found that 1.0 mug/ml (MIC/6.25) of azithromycin suppressed the expression of MexAB-OprM by about 70%, with the result that the cells became two- to fourfold more susceptible to antibiotics such as aztreonam, tetracycline, carbenicillin, chloramphenicol, and novobiocin.

  15. 21 CFR 558.15 - Antibiotic, nitrofuran, and sulfonamide drugs in the feed of animals.

    Science.gov (United States)

    2010-04-01

    ... sulfonamide drugs whether granted by approval of new animal drug applications, master files and/or antibiotic... Veterinary Medicine on protocol design and plans for future studies. (2) By April 20, 1974, data from... Chickens ......do To extend period of high egg production, to improve feed efficiency, to improve egg...

  16. Deciphering the bacterial microbiome in huanglongbing-affected citrus treated with thermotherapy and sulfonamide antibiotics

    Science.gov (United States)

    Huanglongbing (HLB) is a serious citrus disease that threatens the citrus industry. In previous studies, sulfonamide antibiotics and heat treatment suppressed ‘Candidatus Liberibacter asiaticus’ (Las), but did not completely eliminate the Las. Furthermore, there are few reports studying the bacteria...

  17. Interaction of nitrogen dioxide with sulfonamide-substituted phthalocyanines: Towards NO2 gas sensor

    Czech Academy of Sciences Publication Activity Database

    Pochekailov, Sergii; Nožár, Juraj; Nešpůrek, Stanislav; Rakušan, J.; Karásková, M.

    2012-01-01

    Roč. 169, 5 July (2012), s. 1-9 ISSN 0925-4005 R&D Projects: GA AV ČR KAN400720701; GA MPO FR-TI1/144 Institutional research plan: CEZ:AV0Z40500505 Keywords : phthalocyanine * sulfonamide * nitrogen dioxide Subject RIV: CG - Electrochemistry Impact factor: 3.535, year: 2012

  18. Synthesis of New Thiazole Derivatives Bearing A Sulfonamide Moiety Of Expected Anticancer And Radiosensitizing Activities

    International Nuclear Information System (INIS)

    Mohamed, S.Sh.I.

    2012-01-01

    In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new pyrano thiazole and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

  19. ipso-Hydroxylation and Subsequent Fragmentation: a Novel Microbial Strategy To Eliminate Sulfonamide Antibiotics

    NARCIS (Netherlands)

    Ricken, B.; Corvini, P.F.X.; Cichocka, D.; Parisi, M.; Lenz, M.; Wyss, D.; Martínez-Lavanchyd, P.M.; Müller, J.M.; Shahgaldiane, P.; Tulli, L.G.; Kohler, H.P.E.; Kolvenbacha, B.A.

    2013-01-01

    Sulfonamide antibiotics have a wide application range in human and veterinary medicine. Because they tend to persist in the environment, they pose potential problems with regard to the propagation of antibiotic resistance. Here, we identified metabolites formed during the degradation of

  20. Rapid immunochemical analysis of the sulfonamide-sugar conjugated fraction of antibiotic contaminated honey samples.

    Science.gov (United States)

    Muriano, A; Chabottaux, V; Diserens, J-M; Granier, B; Sanchez-Baeza, F; Marco, M-P

    2015-07-01

    A rapid high-throughput immunochemical screening (HtiS) procedure for the analysis of the sulfonamide (SA)-sugar conjugated fraction of antibiotic contaminated honey samples has been developed. Studies performed with this matrix have indicated that sulfonamide antibiotics are conjugated to sugars rapidly and quantitatively, providing samples with very low SA immunoreactivity. Therefore, sulfonamides must be first released before the analysis, and for this purpose, a simple and fast sample preparation procedure has been established consisting of hydrolyzing the sample for 5 min, adjusting the pH and buffering the sample prior to the immunochemical analysis. Under these conditions, honey samples could be directly analyzed without any additional sample treatment, other than dilution. Recovery values of the whole analytical procedure were greater than 85%. The analysis of the same samples without the hydrolysis provided recovery values below 5%. Selectivity studies performed in hydrolyzed honey samples revealed that nine relevant sulfonamide antibiotics can be detected with limit of detection (LOD) values below the action limits established by some EU countries (Belgium, 20 μg kg(-1), United Kingdom or Switzerland, 50 μg kg(-1)). Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Computational study of substituent effects on the acidity, toxicity and chemical reactivity of bacteriostatic sulfonamides.

    Science.gov (United States)

    Soriano-Correa, Catalina; Barrientos-Salcedo, Carolina; Francisco-Márquez, Misaela; Sainz-Díaz, C Ignacio

    2018-02-16

    Relationships among physicochemical properties, the chemical structure and antibacterial activity of sulfonamides have not been completely explicated yet. Nevertheless, from a therapeutics and prodrugs design point of view, a substituent group can modify the electronic structure, the physicochemical features and chemical reactivity which are critical for the biological activity. In this work, we analyze the substituent effects on the physicochemical properties, toxicity, chemical reactivity and its relation with the bacteriostatic activity of selected sulfonamides by means of DFT-M06-2X calculations in aqueous solution, using quantum chemical and docking descriptors. A correlation between the theoretical acidity and the pKa experimental values has been found. The more active sulfonamides have a larger acidity. The acidity increases with electron-withdrawing substituents. The main reactivity takes place on N4 atoms linked to aromatic ring, and in the SO 2 NH moiety, which are influenced by substituents. Docking descriptors showed binding affinities between sulfonamides and target receptor, the dihydropteroate synthase (DHPS). Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Direct Spirocyclization from Keto-sulfonamides: An Approach to Azaspiro Compounds.

    Science.gov (United States)

    Beltran, Frédéric; Fabre, Indira; Ciofini, Ilaria; Miesch, Laurence

    2017-10-06

    Spontaneous spirocyclization of keto-sulfonamides via ynamides through a one-pot process is presented. Push-pull ynamides were obtained through Michael addition/elimination without Cu. The obtained azaspiro compounds are building blocks for indole alkaloids. Theoretical studies provide insights into the mechanism of the formal Conia-ene reaction.

  3. Biosensor immunoassay for the detection of eight sulfonamides in chicken serum

    NARCIS (Netherlands)

    Haasnoot, W.; Bienenmann-Ploum, M.; Kohen, F.

    2003-01-01

    A monoclonal antibody (MAb) raised against sulfamethazine (21C7) was applied in an optical biosensor (Biacore Q) to develop a rapid biosensor immunoassay (BIA) for the detection of several sulfonamides in chicken serum. The performance of this MAb was compared with two polyclonal antibodies (PAbs)

  4. Ferrate promoted oxidative cleavage of sulfonamides: Kinetics and product formation under acidic conditions

    Science.gov (United States)

    Sulfonamide-based antibiotics are often detected in surface waters and secondary wastewater effluents and pose an eminent threat for the development of antibiotic resistance bacteria and genes in aquatic environment. This paper presents the kinetics and stoichiometry of the oxid...

  5. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15.

    Science.gov (United States)

    Han, Ting; Goralski, Maria; Gaskill, Nicholas; Capota, Emanuela; Kim, Jiwoong; Ting, Tabitha C; Xie, Yang; Williams, Noelle S; Nijhawan, Deepak

    2017-04-28

    Indisulam is an aryl sulfonamide drug with selective anticancer activity. Its mechanism of action and the basis for its selectivity have so far been unknown. Here we show that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. Mutations in RBM39 that prevent its recruitment to CUL4-DCAF15 increase RBM39 stability and confer resistance to indisulam's cytotoxicity. RBM39 associates with precursor messenger RNA (pre-mRNA) splicing factors, and inactivation of RBM39 by indisulam causes aberrant pre-mRNA splicing. Many cancer cell lines derived from hematopoietic and lymphoid lineages are sensitive to indisulam, and their sensitivity correlates with DCAF15 expression levels. Two other clinically tested sulfonamides, tasisulam and chloroquinoxaline sulfonamide, share the same mechanism of action as indisulam. We propose that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides). Copyright © 2017, American Association for the Advancement of Science.

  6. Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

    Science.gov (United States)

    Angius, Fabrizio; Piras, Enrica; Uda, Sabrina; Madeddu, Clelia; Serpe, Roberto; Bigi, Rachele; Chen, Wuguo; Dittmer, Dirk P; Pompei, Raffaello; Ingianni, Angela

    2017-08-01

    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.

  7. Rapid disease progression in human immunodeficiency virus type 1-infected individuals with adverse reactions to trimethoprim-sulfamethoxazole prophylaxis

    NARCIS (Netherlands)

    Veenstra, J.; Veugelers, P. J.; Keet, I. P.; van der Ven, A. J. A. M.; Miedema, F.; Lange, J. M.; Coutinho, R. A.

    1997-01-01

    We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid

  8. dfrA25, a novel trimethoprim resistance gene from Salmonella Agona isolated from a human urine sample in Brazil

    DEFF Research Database (Denmark)

    Agersø, Yvonne; Peirano, Gisele; Aarestrup, Frank Møller

    2006-01-01

    . A phylogenetic tree was constructed based on representative trimethoprim-resistance-mediating DfrA proteins retrieved from GenBank. Filter-mating experiments and Southern blots of plasmid preparations were performed with the donor and selected transconjugants. Results and conclusions: dfrA25 encodes...

  9. Effectiveness of trimethoprim/sulfamethoxazole for children with chronic active otitis media: a randomized, placebo-controlled trial.

    NARCIS (Netherlands)

    van der Veen, E.L.; Rovers, M.M.; Albers, F.W.J.; Sanders, E.A.M.; Schilder, A.G.M.

    2007-01-01

    OBJECTIVE: The goal was to determine the clinical effectiveness of prolonged outpatient treatment with trimethoprim/sulfamethoxazole for children with chronic active otitis media. METHODS: We performed a randomized, placebo-controlled trial with 101 children (1-12 years of age) with chronic active

  10. Prevention of Pneumocystis carinii pneumonia relapse in AIDS patients. The efficacy and tolerability of low-dose sulfamethoxazole-trimethoprim

    DEFF Research Database (Denmark)

    Nielsen, T L; Jensen, Birgitte Nybo; Nelsing, S

    1993-01-01

    The effectiveness and tolerability of Sulfamethoxazole with Trimethoprim (SMX-TMP), a dose of 400mg/80mg given twice a day as secondary prophylaxis (SP) against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 166 AIDS patients. The mean observation period was 9.7 months (range...

  11. Towards the Understanding of Resistance Mechanisms in Clinically Isolated Trimethoprim-resistant, Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Frey, K.; Lombardo, M; Wright, D; Anderson, A

    2010-01-01

    Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.

  12. A community-based study of the incidence of trimethoprim-sulfamethoxazole-preventable infections in Malawian adults living with HIV.

    NARCIS (Netherlands)

    Oosterhout, J.J.G. van; Laufer, M.K.; Graham, S.M.; Thumba, F.; Perez, M.A.; Chimbiya, N.; Wilson, L.; Chagomerana, M.; Molyneux, M.E.; Zijlstra, E.E; Taylor, T.E.; Plowe, C.V.

    2005-01-01

    The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair

  13. Airborne allergic contact dermatitis from tylosin in pharmacy compounders and cross-sensitization to macrolide antibiotics.

    Science.gov (United States)

    Malaiyandi, Viba; Houle, Marie Claude; Skotnicki-Grant, Sandy

    2012-01-01

    Tylosin is a broad-spectrum macrolide antibiotic that is restricted to veterinary use. Allergic contact dermatitis (ACD) caused by tylosin has been reported in the literature from the farming industry and veterinary medicine. It is also reported as the most common antibiotic to cause ACD in the previously mentioned occupational settings. We present 2 cases of airborne ACD from tylosin among veterinary pharmaceutical compounding technicians. To our knowledge, only one other case of patch test-confirmed tylosin ACD has been reported in the manufacturing setting. Based on our results, cross-sensitization to other clinically relevant macrolides does not appear to be a concern. Our cases highlight the importance of patch testing among pharmaceutical compounders where the incidence of an airborne contact may be greater, given that the exposure is to the powdered form of potential allergens.

  14. A review of macrolide treatment of atherosclerosis and abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Stovring, Jette; Andersen, Paul Lehm

    2003-01-01

    Seroepidemiological studies have shown an association between Chlamydia pneumoniae and atherosclerosis, the risk of acute myocardial infarction and abdominal aortic aneurysms (AAA). Several studies have detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in AAA......, and in sclerotic aortic valves. However, culturing of C. pneumoniae is difficult and has seldomly succeeded from atherosclerotic lesions. Thus, the pathogenicity is unknown, and the significance of detecting the organism is unresolved. Nevertheless, in a large observational study comparing the risk...... of cardiovascular events among recipients of macrolide versus pencillins, macrolide treatment reduced the risk of such events after relevant adjustment. Furthermore, in two out of three minor randomized clinical trials were patients with ischaemic heart disease were randomized into antibiotic treated and placebo...

  15. Potential chemopreventive activity of a new macrolide antibiotic from a marine-derived Micromonospora sp.

    Science.gov (United States)

    Carlson, Skylar; Marler, Laura; Nam, Sang-Jip; Santarsiero, Bernard D; Pezzuto, John M; Murphy, Brian T

    2013-04-03

    Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1), as well as 5-O-α-L-rhamnosyltylactone (2), were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses.

  16. Susceptibility of bacterial isolates from community-acquired infections in sub-Saharan Africa and Asia to macrolide antibiotics.

    Science.gov (United States)

    Lubell, Yoel; Turner, Paul; Ashley, Elizabeth A; White, Nicholas J

    2011-10-01

    To review the literature on the susceptibility of common community pathogens in sub-Saharan Africa and Asia to the macrolide antibiotics. Inclusion criteria required that isolates were collected since 2004 to ensure results were of contemporary relevance. The data were aggregated by region, age group and sterility of site of culture sample. A total of 51 studies were identified, which reported the macrolide antimicrobial susceptibilities of common bacterial pathogens isolated since 2004. In general, there was less macrolide resistance in African than in Asian isolates. Most African studies reported high levels of macrolide susceptibility in Streptococcus pneumoniae, whereas most Chinese studies reported high levels of resistance. There was very little information available for Gram-negative organisms. Susceptibility of the pneumococcus to macrolides in SSA remains high in many areas, and good activity of azithromycin has been shown against Salmonellae spp. in Asia. In urban areas where high antibiotic consumption is prevalent, there was evidence of increased resistance to macrolides. However, there is no information on susceptibility from large areas in both continents. © 2011 Blackwell Publishing Ltd.

  17. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies

    International Nuclear Information System (INIS)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-01-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m 2 /g), high pore volume (1.23 cm 3 /g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. - Highlights: • A high efficiency adsorbent for sulfonamide removal is prepared from anthracite. • Effects of

  18. Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai, China.

    Science.gov (United States)

    Martin, Irene E; Gu, Weiming; Yang, Yang; Tsang, Raymond S W

    2009-08-15

    The resurgence of syphilis in China requires laboratories to update their methods for molecular epidemiology investigation and surveillance. This study focuses on implementing polymerase chain reaction (PCR) diagnostic tests for syphilis and for detection of molecular subtypes and macrolide resistance among strains causing primary syphilis in the city of Shanghai, China. Swabs were obtained from the genital lesions of 39 patients who presented with symptoms compatible with primary syphilis. Eight of the patients also provided whole blood samples. Swabs were also obtained from 10 patients without syphilis who presented with genital ulcers. PCR tests to amplify 3 common but unlinked treponemal genes were performed on DNA samples extracted from these specimens. Molecular subtyping was based on genetic characterization of 2 treponemal repeat genes, arp and tpr. Detection of macrolide resistance was accomplished by identification of the 23S ribosomal RNA gene mutation associated with the resistance pattern. Thirty-eight patients with primary syphilis were found to have Treponema pallidum DNA in their genital lesions by PCR assays using primers that target the bmp, tpp-47, and polA genes. None of the patients without syphilis had positive PCR results. Five molecular subtypes were identified, with 1 type (14f) causing 79% of the cases. All 38 patients were found to be infected with macrolide-resistant strains. Three common treponemal gene targets (bmp, tpp-47, and polA) were detectable by PCR in patients with primary syphilis. A single clone characterized as 14f and showing macrolide resistance appeared to have caused most of the primary syphilis cases in this study.

  19. Macrolides inhibit Fusobacterium nucleatum-induced MUC5AC production in human airway epithelial cells.

    Science.gov (United States)

    Nagaoka, Kentaro; Yanagihara, Katsunori; Harada, Yosuke; Yamada, Koichi; Migiyama, Yohei; Morinaga, Yoshitomo; Hasegawa, Hiroo; Izumikawa, Koichi; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

    2013-04-01

    Fusobacterium nucleatum is one of the most common anaerobic bacteria in periodontitis and is responsible for several extraoral infections, including respiratory tract diseases. In this study, we examined whether F. nucleatum induces mucin secretion in airway epithelial cells. We also examined the effects of macrolides on F. nucleatum-induced mucus production compared with the effects of other antibiotics that exert anti-anaerobic activities. The production of MUC5AC, the major core protein of mucin secreted from the airway surface epithelium, in bronchial epithelial cells after stimulation with culture supernatants (Sup) of F. nucleatum was analyzed by performing enzyme-linked immunosorbent assay and quantitative RT-PCR. The cell-signaling pathway of F. nucleatum Sup stimulation was also analyzed by Western blotting. For inhibition studies, cells were treated with azithromycin, clarithromycin, clindamycin (CLDM), and metronidazole (MTZ). The F. nucleatum Sup induced NCI-H292 cells to express MUC5AC at both the protein level and the mRNA level in both a time- and dose-dependent manner. Macrolides inhibited F. nucleatum Sup-induced MUC5AC production, while CLDM and MTZ were less effective. F. nucleatum Sup induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and this induction was suppressed by macrolides. F. nucleatum Sup-induced MUC5AC production was blocked by the ERK pathway inhibitor U0126. F. nucleatum is likely to contribute to excessive mucin production, which suggests that periodontitis may correlate with the pathogenesis of chronic respiratory tract infection. Macrolides seem to reduce this mucin production and might represent an additional means of therapeutic intervention for F. nucleatum respiratory tract infections other than CLDM and MTZ.

  20. Antimicrobial growth promoter ban and resistance to macrolides and vancomycin in enterococci from pigs

    DEFF Research Database (Denmark)

    Boerlin, P.; Wissing, A.; Aarestrup, Frank Møller

    2001-01-01

    Ninety-six enterococcus isolates from fecal samples of pigs receiving tylosin as an antimicrobial growth promoter and 59 isolates obtained in the same farms 5 to 6 months after the ban of antimicrobial growth promoters in Switzerland were tested for susceptibility to nine antimicrobial agents....... A clear decrease in resistance to macrolides, lincosamides, and tetracycline was visible after the ban. Vancomycin-resistant Enterococcus faecium belonged to the same clonal lineage as vancomycin-resistant isolates previously isolated from Danish pigs....

  1. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027.

    Science.gov (United States)

    Wieczorkiewicz, Jeffrey T; Lopansri, Bert K; Cheknis, Adam; Osmolski, James R; Hecht, David W; Gerding, Dale N; Johnson, Stuart

    2016-01-01

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Does macrolide use confer risk of out-of-hospital cardiac arrest compared with penicillin V?

    DEFF Research Database (Denmark)

    Hertz, Frederik Boetius; Jensen, Aksel; Knudsen, Jenny D

    2018-01-01

    were examined by conditional logistic regression analyses in case-crossover and case-time-control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics. ETHICS: The present study...... was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)). PARTICIPANTS: We identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment....... RESULTS: In the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0...

  3. Subspecies distribution and macrolide and fluoroquinolone resistance genetics of Mycobacterium abscessus in Korea.

    Science.gov (United States)

    Kim, J; Sung, H; Park, J-S; Choi, S-H; Shim, T-S; Kim, M-N

    2016-01-01

    Treating Mycobacterium abscessus infections with antimicrobials remains difficult, possibly due to drug resistance. To investigate the subspecies distribution of M. abscessus and its correlation with antibiotic susceptibility and the genetics of antibiotic resistance, focusing on macrolides and fluoroquinolones, in the Republic of Korea. A total of 53 M. abscessus isolates were identified to the subspecies level by sequencing of hsp65 and erm(41). The minimal inhibitory concentrations (MICs) of clarithromycin (CLM) and ciprofloxacin (CFX) were determined using Sensititre™ RAPMYCO plates. The rrl, gyrA and gyrB genes were sequenced to elucidate the molecular mechanisms of macrolide and fluoroquinolone resistance. Isolates included 22 M. abscessus subsp. abscessus and 31 M. abscessus subsp. bolletii. erm(41) sequences showing subspecies-specific deletions and sequence variations in the 28th nucleotide were concordant with inducible CLM resistance; however, mutations in rrl were not detected. Low- and high-level CFX resistance was observed in respectively 19 (35.8%) and 10 (18.9%) of the 53 clinical isolates, regardless of subspecies. However, no non-synonymous mutations were detected in gyrA or gyrB. Sequencing of the erm gene and subspeciation of M. abscessus may be used to predict inducible macrolide susceptibility. Further studies of the relationship between specific mutations in gyrA or gyrB to MIC change are required.

  4. Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

    Science.gov (United States)

    Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

    2015-08-01

    Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Mycoplasma genitalium in Spain: prevalence of genital infection and frequency of resistance to macrolides.

    Science.gov (United States)

    Asenjo, Alejandra; Kusters, Johannes G; Severs, Tim T; Alós, Juan-Ignacio

    2018-03-01

    The aim of this study was to determine the prevalence of Mycoplasma genitalium infection and the resistance to macrolides within a general population in Madrid in 2015. We collected 359 urine samples from a general population with symptoms of sexually transmitted infections (STIs). All samples underwent a real-time PCR. For the detection of macrolide resistance, a 283bp fragment of region V of the 23S rRNA gene of M. genitalium was amplified and sequenced. We found a prevalence of 3.34% of M. genitalium and a macrolide resistance rate of 20%. In males, the prevalence was 6.62% and in women 0.96%, being significantly higher in males. The prevalence obtained shows that it is a pathogen to consider in our environment. These findings stress the need for routine testing of M. genitalium infections and would seem to suggest the advisability of resistance testing. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. In vitro killing kinetics and postantibiotic effect of josamycin and other macrolides on several bacteria.

    Science.gov (United States)

    Minguez, F; Ramos, C; Loscos, A; Chiu, M L; Prieto, J

    1993-01-01

    The antimicrobial activity [minimal inhibitory concentration (MIC) and killing kinetics] and postantibiotic effect (PAE) of different concentrations (MIC and 10 x MIC) of josamycin, erythromycin, midecamycin and azithromycin on Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli were studied in vitro. The MIC and killing kinetics were determined by standard methods. The PAE was measured after 1 h exposure to the drugs, which were removed by diluting the culture 1,000-fold. All tested macrolides had their lowest MIC against S. pneumoniae, and the most active against S. aureus was josamycin. In killing kinetics, using 10 x MIC, the macrolides exhibited a bactericidal effect against S. pneumoniae and E. coli, with reductions of 3 log10 in colony-forming units per milliliter with respect to the initial inoculum, while a bactericidal effect was not observed for S. aureus. The PAEs were concentration dependent, the greatest PAEs being obtained with S. pneumoniae. Although lower, the PAEs induced on E. coli were significant when high concentrations of the drug were tested. The assayed macrolides showed both more activity and PAEs on S. pneumoniae.

  7. Marinisporolides, polyene-polyol macrolides from a marine actinomycete of the new genus Marinispora.

    Science.gov (United States)

    Kwon, Hak Cheol; Kauffman, Christopher A; Jensen, Paul R; Fenical, William

    2009-01-16

    Two new polyene macrolides, marinisporolides A and B (1, 2), were isolated from the saline culture of the marine actinomycete, strain CNQ-140, identified as a member of the new marine genus Marinispora. The marinisporolides are 34-membered macrolides composed of a conjugated pentaene and several pairs of 1,3-dihydroxyl functionalities. Marinisporolide A (1) contains a bicyclic spiro-bis-tetrahydropyran ketal functionality, while marinisporolide B (2) is the corresponding hemiketal. The structures of these new compounds were assigned by combined spectral and chemical methods including extensive 2D NMR experiments and correlations of (13)C NMR data with Kishi's Universal NMR Database. Chemical modifications, including methanolysis, acetonide formation, and application of the modified Mosher method, provided the full stereostructures of these molecules. Three additional macrolides, marinisporolides C-E (3-5), which are olefin geometric isomers of marinisporolide A (1), were also isolated and their structures defined. Under room light, marinisporolides A and B readily photoisomerize to C-E indicating that they are most likely produced by photochemical conversion during the cultivation or isolation procedures. Although polyenes, marinisporolides A (1) and B (2) showed weak to no antifungal activity against Candida albicans.

  8. Marinisporolides, Polyene-Polyol Macrolides from a Marine Actinomycete of the New Genus “Marinispora”

    Science.gov (United States)

    Kwon, Hak Cheol; Kauffman, Christopher A.; Jensen, Paul R.; Fenical, William

    2011-01-01

    Two new polyene macrolides, marinisporolides A and B (1, 2), were isolated from the saline culture of the marine actinomycete, strain CNQ-140, identified as a member of the new marine genus “Marinispora.” The marinisporolides are 34 membered macrolides composed of a conjugated pentaene and several pairs of 1,3-dihydroxyl functionalities. Marinisporolide A (1) contains a bicyclic spiro-bis-tetrahydropyran ketal functionality, while marinisporolide B (2) is the corresponding hemiketal. The structures of these new compounds were assigned by combined spectral and chemical methods including extensive 2D NMR experiments and correlations of 13C NMR data with Kishi’s Universal NMR Database. Chemical modifications, including methanolysis, acetonide formation, and application of the modified Mosher method, provided the full stereostructures of these molecules. Three additional macrolides, marinisporolides C–E (3–5), which are olefin geometric isomers of marinisporolide A (1), were also isolated and their structures defined. Under room light, marinisporolides A and B readily photoisomerize to C–E indicating that they are most likely produced by photochemical conversion during the cultivation or isolation procedures. Although polyenes, marinisporolides A (1) and B (2) showed weak to no antifungal activity against Candida albicans. PMID:19132943

  9. Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mikailov A

    2013-01-01

    Full Text Available Anar Mikailov,1 Ilona Kane,2 Stephen C Aronoff,3 Raemma Luck,3,† Michael T DelVecchio31Beth Israel Deaconess Medical Center, Boston, MA, 2St Christopher's Hospital for Children, Philadelphia, PA, 3Department of Pediatrics, Temple University School of Medicine, Philadelphia, PA, USA†Raemma Luck is now deceasedBackground: The purpose of this study was to investigate macrolides as an adjunct to an asthma controller regimen in children with asthma.Methods: Prospective clinical trials of macrolide therapy in children with asthma using outcome measures of change in forced expiratory volume in one second (FEV1 and/or oral corticosteroid requirement were searched for in PubMed up to December 2009. The reference lists of studies were also included in the analysis, as well as those listed in published meta-analyses.Results: The literature search yielded 116 studies, six of which were included in this meta-analysis. The change in FEV1 from baseline with adjunctive use of macrolide therapy in all children was not significant (0.25% predicted; 95% confidence interval [CI] −0.37, 0.86 predicted, P = 0.43; however, the change in FEV1 among children receiving daily oral corticosteroids was significant (3.89% predicted; 95% CI −0.01, 7.79, P = 0.05. Addition of macrolide therapy to the treatment of children with oral corticosteroid-dependent asthma resulted in a statistically significant decrease in daily corticosteroid dosage (−3.45 mg/day; 95% CI −5.79, −1.09 mg/day, P = 0.004. This reduction in daily corticosteroid dosage was directly proportional to the duration of macrolide therapy (−0.17 mg methylprednisolone per week of macrolide therapy; 95% CI −0.33, −0.021, P = 0.025.Conclusion: Addition of macrolides to the treatment regimen of children with oral corticosteroid-dependent asthma improves FEV1 and decreases the daily dosage of corticosteroids required for control in these children. The degree of dose reduction is directly related to

  10. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human

    DEFF Research Database (Denmark)

    Shuyu, Wu; Dalsgaard, A.; Hammerum, A. M.

    2010-01-01

    involved in the mobility of sul genes. Methods A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multiplex PCR was conducted to detect the presence of three sul genes among the sulfonamide-resistant E. coli......Background Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3) in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids...... carrying sul genes were characterized by PCR-based replicon typing to allow a comparison of the types of sul genes, the reservoir and plasmid present. Results A total of 109/501 isolates exhibited sulfonamide resistance. The relative prevalences of sul genes from the three reservoirs (pigs, pig carcasses...

  11. L-Threonine-derived novel bifunctional phosphine-sulfonamide catalyst-promoted enantioselective aza-morita-Baylis-Hillman reaction

    KAUST Repository

    Zhong, Fangrui

    2011-03-18

    A series of novel bifunctional phosphine-sulfonamide organic catalysts were designed and readily prepared from natural amino acids, and they were utilized to promote enantioselective aza-Morita-Baylis-Hillman (MBH) reactions. l-Threonine-derived phosphine-sulfonamide 9b was found to be the most efficient catalyst, affording the desired aza-MBH adducts in high yields and with excellent enantioselectivities. © 2011 American Chemical Society.

  12. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies.

    Science.gov (United States)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-04-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m(2)/g), high pore volume (1.23 cm(3)/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A sensitive method for the determination of Sulfonamides in seawater samples by Solid Phase Extraction and UV-Visible spectrophotometry

    Science.gov (United States)

    Errayess, Sophia Ait; Lahcen, Abdellatif Ait; Idrissi, Laila; Marcoaldi, Caterina; Chiavarini, Salvatore; Amine, Aziz

    2017-06-01

    The authors have developed a sensitive spectrophotometric method for determination of sulfonamide derivatives such as sulfanilamide (SAA), sulfadiazine (SDZ), sulfacetamide (SCT) sulfamethoxazole (SMX), sulfamerazine (SMR), sulfadimethoxine (SDX), sulfamethiazole (SMT) and Sulfathiazole (STZ). This method is based on the Bratton-Marshall reaction, which involves the diazotization of sulfonamides with sodium nitrite under acidic conditions, followed by coupling with N-(1-naphtyl) ethylenediamine dihydrochloride (NED) to form a pink colored compound. Therefore, the Bratton-Marshall method was modified by optimizing the reaction conditions, which allows us to determine a low concentration range of sulfonamides compared to the reported methods. The limits of detection and quantification obtained were 0.019-0.05 and 0.06-0.16 μg mL- 1, respectively. In comparison with other reported methods using different coupling agents, the proposed method was found to be the most simple and sensitive for sulfonamides determination. In this paper, the modified method was successfully employed for the determination of sulfonamides in drinking water, seawater and pharmaceutical and veterinary formulations. The purpose of this work is to optimize and develop a simple method for extraction and concentration of sulfonamides present as residues in seawater and their quantification with the recommended spectrophotometric method. Solid phase extraction (SPE) of sulfonamides from seawater samples was evaluated using Oasis HLB cartridges (3 mL, 540 mg). The recovery efficiency was investigated in the sulfonamides concentration range comprised between 0.19 and 126 ng mL- 1. The ease of use of this extraction method makes it very useful for routine laboratory work.

  14. Ultrasensitive Immunochromatographic Strip for Fast Screening of 27 Sulfonamides in Honey and Pork Liver Samples Based on a Monoclonal Antibody.

    Science.gov (United States)

    Chen, Yanni; Guo, Lingling; Liu, Liqiang; Song, Shanshan; Kuang, Hua; Xu, Chuanlai

    2017-09-20

    Group-specific monoclonal antibodies (Mabs) with selectivity for 27 sulfonamides were developed based on new combinations of immunogen and coating antigen. The Mab was able to recognize 27 sulfonamides with 50% inhibition concentration (IC 50 ) values ranging from 0.15 to 15.38 μg/L. In particular, the IC 50 values for five sulfonamides (sulfamethazine, sulfaquinoxaline, sulfamonomethoxine, sulfadimethoxine, and sulfamethoxazole) were 0.51, 0.15, 0.56, 0.54, and 2.14 μg/L, respectively. On the basis of the Mab, an immunochromatographic lateral flow strip test was established for rapid screening of sulfonamides in honey samples. The visual limit of detection of the strip test for most sulfonamides in spiked honey samples was below 10 μg/kg, satisfying the requirements of authorities. Positive honey and pork liver samples, which had been confirmed by high-performance liquid chromatography/mass spectrometry, were used to validate the reliability of the proposed strip test. The immunochromatographic lateral flow strip test provides a rapid and convenient method for fast screening of sulfonamides in honey samples.

  15. Liquid chromatographic and spectrophotometric methods for the determination of erythromycin stearate and trimethoprim in tablets

    Directory of Open Access Journals (Sweden)

    Sonia T. Hassib

    2011-12-01

    Full Text Available Simple, accurate and precise reversed-phase liquid chromatographic (LC and spectrophotometric methods have been developed and validated for the determination of erythromycin stearate (ERS and trimethoprim (TMP in mixture. In LC method, chromatographic separation was achieved on a Symmetry® Waters C18 column (150 × 4.6 mm, 5 μm based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (9:acetonitrile:water (25:100:50, v/v/v at a flow rate of 1.6 ml min−1 with UV detection at 210 nm for ERS and 280 nm for TMP. Besides, two spectrophotometric methods were applied after reaction with perchloric acid (12 M which gives a colored product with ERS. Then, the spectral interference between the colored product of ERS and TMP was resolved by either ratio spectra derivative spectrophotometry in the first spectrophotometric method or chemometric techniques, namely classical least-squares (CLS, principal component regression (PCR and partial least-squares regression (PLS in the second spectrophotometric method. The results were statistically compared using one-way analysis of variance (ANOVA. The methods developed were satisfactorily applied to the analysis of the pharmaceutical preparation containing the two drugs and proved to be specific and accurate for the quality control of the cited drugs in pharmaceutical dosage forms.

  16. Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200 patients with paracoccidioidomycosis.

    Science.gov (United States)

    Borges, Sheila Rocha Conceição; Silva, Gilberto Marcelo Sperandio da; Chambela, Mayara da Costa; Oliveira, Raquel de Vasconcellos C de; Costa, Regina Lana Braga; Wanke, Bodo; Valle, Antonio Carlos Francesconi do

    2014-04-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Brazil accounts for approximately 80% of cases, where it represents a major public health issue due to its disabling impact and the number of premature deaths it causes. We present a retrospective cohort study that was conducted in order to better understand factors that relate to cure of the infection in the treatment of 200 patients with PCM. We evaluated the influence of sociodemographic and clinical factors as well as therapeutic regimen (trimethoprim-sulfamethoxazole [TMP-SMX] and itraconazole) on the progress of PCM (cure and noncure). There was a higher incidence of cure (83%) among patients who regularly received treatment for their infections and completed the treatment protocol. Moreover, itraconazole (86.4%) was significantly superior to TMP-SMX (51.3%) in terms of cure rate and had a median treatment period that was significantly shorter (12 months) than that for TMP-SMX (23 months). A Cox proportional hazard regression model showed that use of itraconazole increased the hazard of cure, regardless of sex, age, education, clinical form, completion of treatment, and regularity. Although the results of this study show that itraconazole was the best treatment option for PCM patients, a double-blind, randomized, controlled trial is necessary to confirm this conclusion.

  17. Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess.

    Science.gov (United States)

    Bowen, Asha C; Carapetis, Jonathan R; Currie, Bart J; Fowler, Vance; Chambers, Henry F; Tong, Steven Y C

    2017-01-01

    Skin and soft tissue infections (SSTI) affect millions of people globally, which represents a significant burden on ambulatory care and hospital settings. The role of sulfamethoxazole-trimethoprim (SXT) in SSTI treatment, particularly when group A Streptococcus (GAS) is involved, is controversial. We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or Staphylococcus aureus , including methicillin-resistant (MRSA). We identified 196 studies, and 15 underwent full text review by 2 reviewers. Observational studies, which mainly focused on SSTI due to S aureus , supported the use of SXT when compared with clindamycin or β-lactams. Of 10 randomized controlled trials, 8 demonstrated the efficacy of SXT for SSTI treatment including conditions involving GAS. These findings support SXT use for treatment of impetigo and purulent cellulitis (without an additional β-lactam agent) and abscess and wound infection. For nonpurulent cellulitis, β-lactams remain the treatment of choice.

  18. An Environmental Risk Assessment for Human-Use Trimethoprim in European Surface Waters

    Science.gov (United States)

    Straub, Jürg Oliver

    2013-01-01

    An environmental risk assessment (ERA) for the aquatic compartment in Europe from human use was developed for the old antibiotic Trimethoprim (TMP), comparing exposure and effects. The exposure assessment is based on European risk assessment default values on one hand and is refined with documented human use figures in Western Europe from IMS Health and measured removal in wastewater treatment on the other. The resulting predicted environmental concentrations (PECs) are compared with measured environmental concentrations (MECs) from Europe, based on a large dataset incorporating more than 1800 single MECs. On the effects side, available chronic ecotoxicity data from the literature were complemented by additional, new chronic results for fish and other organisms. Based on these data, chronic-based deterministic predicted no effect concentrations (PNECs) were derived as well as two different probabilistic PNEC ranges. The ERA compares surface water PECs and MECs with aquatic PNECs for TMP. Based on all the risk characterization ratios (PEC÷PNEC as well as MEC÷PNEC) and risk graphs, there is no significant risk to surface waters. PMID:27029296

  19. An Environmental Risk Assessment for Human-Use Trimethoprim in European Surface Waters

    Directory of Open Access Journals (Sweden)

    Jürg Oliver Straub

    2013-03-01

    Full Text Available An environmental risk assessment (ERA for the aquatic compartment in Europe from human use was developed for the old antibiotic Trimethoprim (TMP, comparing exposure and effects. The exposure assessment is based on European risk assessment default values on one hand and is refined with documented human use figures in Western Europe from IMS Health and measured removal in wastewater treatment on the other. The resulting predicted environmental concentrations (PECs are compared with measured environmental concentrations (MECs from Europe, based on a large dataset incorporating more than 1800 single MECs. On the effects side, available chronic ecotoxicity data from the literature were complemented by additional, new chronic results for fish and other organisms. Based on these data, chronic-based deterministic predicted no effect concentrations (PNECs were derived as well as two different probabilistic PNEC ranges. The ERA compares surface water PECs and MECs with aquatic PNECs for TMP. Based on all the risk characterization ratios (PEC÷PNEC as well as MEC÷PNEC and risk graphs, there is no significant risk to surface waters.

  20. Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam

    Science.gov (United States)

    Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

    2015-01-01

    The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples) were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX), 4 ng L-1 sulfadiazine (SDZ), 17 ng L-1 trimethoprim (TRIM), and 12 ng L-1 enrofloxacin (ENRO). These concentrations were lower than the predicted no effect concentrations (PNECs) and minimum inhibitory concentrations (MICs), suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from aquatic environment, yet the persistence of these antibiotics is of concern and might lead to chronic exposure of aquatic organisms as well as humans. PMID:26135396

  1. Trimethoprim-Sulfamethoxazole-Induced Drug Eruption With Eosinophilia and Systemic Symptoms (DRESS).

    Science.gov (United States)

    Antia, Camila; Persad, Leah; Alikhan, Ali

    2017-10-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe and potentially life threatening adverse drug reaction. To help identify DRESS, several criteria have been established; however, there is still a lack of consensus on diagnosis, and clinical judgment is paramount. Here we describe a 24-year-old female who presented with a cutaneous eruption, fever, lymphadenopathy, eosinophilia, facial edema, and elevated liver enzymes four and a half weeks after a 10-day course of Trimethoprim/sulfamethoxazole (TMP/SMX). We used both the RegiSCAR and J-SCAR criteria to show the validity of classifying this case as DRESS, we also comment on the only other three cases, published to date, that had been reported as TMP/SMX induced DRESS. DRESS can be a difficult diagnosis due to its diverse symptomatology and delayed presentation - therefore, high suspicion and exclusion of other causes is key. Use of validated diagnostic criteria can aid the clinician in this regard. In the absence of a well-established therapy, early recognition, withdrawal of suspected drug(s), and supportive care play a crucial role in the management of DRESS. J Drugs Dermatol. 2017;16(10):1043-1046..

  2. Removal of trimethoprim, sulfamethoxazole, and triclosan by the green alga Nannochloris sp.

    Science.gov (United States)

    Bai, Xuelian; Acharya, Kumud

    2016-09-05

    Trimethoprim (TMP), sulfamethoxazole (SMX), and triclosan (TCS) are widely used and continuously released into aquatic environments. Freshwater algae can be responsible for the uptake and transfer of the contaminants because they are a major food source for most aquatic organisms. This research applied incubation studies to evaluate the removal efficiency of TMP, SMX, and TCS by the green alga Nannochloris sp. The results showed that the hydrophilic antibiotics TMP and SMX remained in the algal culture at 100% and 68%, respectively, after 14days of incubation, and therefore were not significantly removed from the medium. However, the lipophilic antimicrobial TCS was significantly removed from the medium. Immediately after incubation began, 74% of TCS dissipated and 100% of TCS was removed after 7days of incubation. Additionally, over 42% of TCS was found associated with the algal cells throughout the incubation. The results demonstrate that the presence of Nannochloris sp. eliminated TCS in the aquatic system, but could not significantly remove the antibiotics TMP and SMX. The removal mechanisms of SMX and TCS were found to be different in the algal culture. Algae-promoted photolysis was the primary process for removing SMX and algae-mediated uptake played a major role in removing TCS. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

    Directory of Open Access Journals (Sweden)

    Carmen Rodriguez-Cerdeira

    2012-01-01

    Full Text Available Background. Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders. Materials and Methods. We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience. Results. Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus act by inhibiting the activation of the nuclear factor for activated T cells (NFAT. There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet’s disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects. Conclusions. This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders.

  4. The neutral species of the weak base trimethoprim is more toxic to willow trees (Salix viminalis) than the cation

    DEFF Research Database (Denmark)

    Mikes, O.; Trapp, Stefan

    2011-01-01

    The acute toxicity of the veterinary antibiotic trimethoprim (TMP) to willow trees was tested at three different pH levels in hydroponic solutions with TMP concentrations of 1, 10, 100 or 1000 mg/L. The pH variation was achieved by using ammonium (pH 4.3, low) or nitrate (pH 6.4, medium) as nitro......The acute toxicity of the veterinary antibiotic trimethoprim (TMP) to willow trees was tested at three different pH levels in hydroponic solutions with TMP concentrations of 1, 10, 100 or 1000 mg/L. The pH variation was achieved by using ammonium (pH 4.3, low) or nitrate (pH 6.4, medium...

  5. Rationalization of Activity Cliffs of a Sulfonamide Inhibitor of DNA Methyltransferases with Induced-Fit Docking

    Directory of Open Access Journals (Sweden)

    José L. Medina-Franco

    2014-02-01

    Full Text Available Inhibitors of human DNA methyltransferases (DNMT are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure–activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of ‘activity cliffs’, e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

  6. Bismuth- and hafnium-catalyzed hydroamination of vinyl arenes with sulfonamides, carbamates, and carboxamides.

    Science.gov (United States)

    Qin, Hongbo; Yamagiwa, Noriyuki; Matsunaga, Shigeki; Shibasaki, Masakatsu

    2007-01-08

    Catalytic intermolecular hydroamination of vinyl arenes is described. Our initial investigation revealed that a Bi(OTf)3/[Cu(CH3CN)4]PF6 system previously developed for catalytic intermolecular hydroamination of 1,3-dienes was suitable for hydroamination of a styrene with sulfonamides, but the substrate generality of this system was unsatisfactory. Several metals were screened to expand the substrate scope, and a new Hf(OTf)4/[Cu(CH3CN)4]PF6 system was determined to be highly suitable. The combination of Hf(OTf)4 and [Cu(CH3CN)4]PF6 efficiently promoted the hydroamination of various vinyl arenes, including less-reactive vinyl arenes with electron-withdrawing groups. This strategy was applied to sulfonamides, carbamates, and carboxamides, and products were obtained in up to 99% yield with 0.3-10 mol % catalyst loading.

  7. Distribution of quinolones, sulfonamides, tetracyclines in aquatic environment and antibiotic resistance in Indochina

    Directory of Open Access Journals (Sweden)

    Satoru eSuzuki

    2012-02-01

    Full Text Available Southeast Asia has become the center of rapid industrial development and economic growth. However, this growth has far outpaced investment in public infrastructure, leading to the unregulated release of many pollutants, including wastewater-related contaminants such as antibiotics. Antibiotics are of major concern because they can easily be released into the environment from numerous sources, and can subsequently induce development of antibiotic-resistant bacteria. Recent studies have shown that for some categories of drugs this source-to-environment antibiotic resistance relationship is more complex. This review summarizes current understanding regarding the presence of quinolones, sulfonamides, and tetracyclines in aquatic environments of Indochina and the prevalence of bacteria resistant to them. Several noteworthy findings are discussed: 1 quinolone contamination and the occurrence of quinolone resistance are not correlated; 2 occurrence of the sul sulfonamide resistance gene varies geographically; and 3 microbial diversity might be related to the rate of oxytetracycline resistance.

  8. Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII

    Directory of Open Access Journals (Sweden)

    Vaida Morkūnaitė

    2014-01-01

    Full Text Available A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA and isothermal titration calorimetry (ITC. Saccharin bound the CAs weakly, exhibiting the affinities of 1–10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1–10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.

  9. Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas

    Science.gov (United States)

    Ekoue-Kovi, Kekeli; Yearick, Kimberly; Iwaniuk, Daniel P.; Natarajan, Jayakumar K.; Alumasa, John; de Dios, Angel C.; Roepe, Paul D.; Wolf, Christian

    2009-01-01

    We report the synthesis and in vitro antimalarial activities of more than 50 7-chloro-4-aminoquinolyl-derived sulfonamides 3-8 and 11-26, ureas 19-22, thioureas 23-26, and amides 27-54. Many of the CQ analogues prepared for this study showed submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strains of P. falciparum) and low resistance indices were obtained in most cases. Systematic variation of the side chain length and introduction of fluorinated aliphatic and aromatic termini revealed promising leads that overcome CQ resistance. In particular, sulfonamide 3 exhibiting a short side chain with a terminal dansyl moiety combined high antiplasmodial potency with a low resistance index and showed IC50‘s of 17.5 nM and 22.7 nM against HB3 and Dd2 parasites. PMID:19041248

  10. Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin.

    Science.gov (United States)

    Basanagouda, Mahantesha; Shivashankar, K; Kulkarni, Manohar V; Rasal, Vijaykumar P; Patel, Harishchandra; Mutha, Sumit S; Mohite, Ashwini A

    2010-03-01

    A series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl group have been synthesized as antimicrobials in three steps starting from 7-methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was found to yield the corresponding 6-sulfonylchloride 2, which when treated with sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The chemical structures of the compounds were elucidated by IR, NMR and LC-MS spectral data. All the synthesized compounds have been screened for their in vitro anti-bacterial and anti-fungal activities. Some of the compounds have been found to be active against both bacterial species at a concentration of 1 microg/mL. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  11. Rationalization of activity cliffs of a sulfonamide inhibitor of DNA methyltransferases with induced-fit docking.

    Science.gov (United States)

    Medina-Franco, José L; Méndez-Lucio, Oscar; Yoo, Jakyung

    2014-02-21

    Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure-activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of 'activity cliffs', e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

  12. Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents.

    Science.gov (United States)

    Shah, Syed Shoaib Ahmad; Rivera, Gildardo; Ashfaq, Muhammad

    2013-01-01

    Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.

  13. Chemical genetic screening identifies sulfonamides that raise organellar pH and interfere with membrane traffic.

    Science.gov (United States)

    Nieland, Thomas J F; Feng, Yan; Brown, Jing Xu; Chuang, Tuan Daniel; Buckett, Peter D; Wang, Jin; Xie, Xiao-Song; McGraw, Timothy E; Kirchhausen, Tomas; Wessling-Resnick, Marianne

    2004-07-01

    Chemical genetics seeks to identify small molecules that afford functional dissection of cell biological pathways. Previous screens for small molecule inhibitors of exocytic membrane traffic yielded the identification and characterization of several compounds that block traffic from the Golgi to the cell surface as well as transport from the endoplasmic reticulum to the Golgi network [Feng et al. Proc Natl Acad Sci USA 2003;100:6469-6474; Yarrow et al. Comb Chem High Throughput Screen 2003;6:279-286; Feng et al. EMBO Reports 2004: in press]. Here, we screened these inhibitors for potential effects on endocytic membrane traffic. Two structurally related sulfonamides were found to be potent and reversible inhibitors of transferrin-mediated iron uptake. These inhibitors do not block endoplasmic reticulum-to-Golgi transport, but do disrupt Golgi-to-cell surface traffic. The compounds are members of a novel class of sulfonamides that elevate endosomal and lysosomal pH, down-regulate cell surface receptors, and impair recycling of internalized transferrin receptors to the plasma membrane. In vitro experiments revealed that the sulfonamides directly inhibit adenosine triphosphate (ATP) hydrolysis by the V-ATPase and that they also possess a potent proton ionophore activity. While maintenance of organellar pH is known to be a critical factor in both endocytosis and exocytosis, the precise role of acidification, beyond the uncoupling of ligands from their receptors, remains largely unknown. Identification of this novel class of sulfonamide inhibitors provides new chemical tools to better understand the function of organelle pH in membrane traffic and the activity of V-ATPases in particular.

  14. Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

    Energy Technology Data Exchange (ETDEWEB)

    Cumming, Jared; Babu, Suresh; Huang, Ying; Carrol, Carolyn; Chen, Xia; Favreau, Leonard; Greenlee, William; Guo, Tao; Kennedy, Matthew; Kuvelkar, Reshma; Le, Thuy; Li, Guoqing; McHugh, Nansie; Orth, Peter; Ozgur, Lynne; Parker, Eric; Saionz, Kurt; Stamford, Andrew; Strickland, Corey; Tadesse, Dawit; Voigta, Johannes; Zhang, Lili; Zhang, Qi (Ligand); (Merck)

    2010-08-17

    With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2{prime} sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A{beta}{sub 40} in transgenic mice with a single subcutaneous dose.

  15. Deciphering the Bacterial Microbiome in Huanglongbing-Affected Citrus Treated with Thermotherapy and Sulfonamide Antibiotics.

    Directory of Open Access Journals (Sweden)

    Chuanyu Yang

    Full Text Available Huanglongbing (HLB is a serious citrus disease that threatens the citrus industry. In previous studies, sulfonamide antibiotics and heat treatment suppressed 'Candidatus Liberibacter asiaticus' (Las, but did not completely eliminate the Las. Furthermore, there are few reports studying the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics. In this study, combinations of heat (45°C or 40°C and sulfonamide treatment (sulfathiazole sodium-STZ, or sulfadimethoxine sodium-SDX were applied to HLB-affected citrus. The bacterial microbiome of HLB-affected citrus following thermotherapy and/or chemotherapy was characterized by PhyloChipTMG3-based metagenomics. Our results showed that the combination of thermotherapy at 45°C and chemotherapy with STZ and SDX was more effective against HLB than thermotherapy alone, chemotherapy alone, or a combination of thermotherapy at 40°C and chemotherapy. The PhyloChipTMG3-based results indicated that 311 empirical Operational Taxonomic Units (eOTUs were detected in 26 phyla. Cyanobacteria (18.01% were dominant after thermo-chemotherapy. Thermotherapy at 45°C decreased eOTUs (64.43% in leaf samples, compared with thermotherapy at 40°C (73.96% or without thermotherapy (90.68% and it also reduced bacterial family biodiversity. The eOTU in phylum Proteobacteria was reduced significantly and eOTU_28, representing "Candidatus Liberibacter," was not detected following thermotherapy at 45°C. Following antibiotic treatment with SDX and STZ, there was enhanced abundance of specific eOTUs belonging to the families Streptomycetaceae, Desulfobacteraceae, Chitinophagaceae, and Xanthomonadaceae, which may be implicated in increased resistance to plant pathogens. Our study further develops an integrated strategy for combating HLB, and also provides new insight into the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics.

  16. Deciphering the Bacterial Microbiome in Huanglongbing-Affected Citrus Treated with Thermotherapy and Sulfonamide Antibiotics.

    Science.gov (United States)

    Yang, Chuanyu; Powell, Charles A; Duan, Yongping; Shatters, Robert; Fang, Jingping; Zhang, Muqing

    2016-01-01

    Huanglongbing (HLB) is a serious citrus disease that threatens the citrus industry. In previous studies, sulfonamide antibiotics and heat treatment suppressed 'Candidatus Liberibacter asiaticus' (Las), but did not completely eliminate the Las. Furthermore, there are few reports studying the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics. In this study, combinations of heat (45°C or 40°C) and sulfonamide treatment (sulfathiazole sodium-STZ, or sulfadimethoxine sodium-SDX) were applied to HLB-affected citrus. The bacterial microbiome of HLB-affected citrus following thermotherapy and/or chemotherapy was characterized by PhyloChipTMG3-based metagenomics. Our results showed that the combination of thermotherapy at 45°C and chemotherapy with STZ and SDX was more effective against HLB than thermotherapy alone, chemotherapy alone, or a combination of thermotherapy at 40°C and chemotherapy. The PhyloChipTMG3-based results indicated that 311 empirical Operational Taxonomic Units (eOTUs) were detected in 26 phyla. Cyanobacteria (18.01%) were dominant after thermo-chemotherapy. Thermotherapy at 45°C decreased eOTUs (64.43%) in leaf samples, compared with thermotherapy at 40°C (73.96%) or without thermotherapy (90.68%) and it also reduced bacterial family biodiversity. The eOTU in phylum Proteobacteria was reduced significantly and eOTU_28, representing "Candidatus Liberibacter," was not detected following thermotherapy at 45°C. Following antibiotic treatment with SDX and STZ, there was enhanced abundance of specific eOTUs belonging to the families Streptomycetaceae, Desulfobacteraceae, Chitinophagaceae, and Xanthomonadaceae, which may be implicated in increased resistance to plant pathogens. Our study further develops an integrated strategy for combating HLB, and also provides new insight into the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics.

  17. Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474.

    Science.gov (United States)

    Gamage, Swarna A; Giddens, Anna C; Tsang, Kit Y; Flanagan, Jack U; Kendall, Jackie D; Lee, Woo-Jeong; Baguley, Bruce C; Buchanan, Christina M; Jamieson, Stephen M F; Shepherd, Peter R; Denny, William A; Rewcastle, Gordon W

    2017-10-15

    Replacement of one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 (1) with sulfonamide containing substituents produced a new class of active and potent PI3Kα inhibitors. Solubility issues prevented all but the 6-amino derivative 17 from being evaluated in vivo, but the clear activity of this compound demonstrated that this class of PI3K inhibitor shows great promise. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Synthesis of Morpholine Containing Sulfonamides: Introduction of Morpholine Moiety on Amine Functional Group

    Directory of Open Access Journals (Sweden)

    D. Singh

    2004-01-01

    Full Text Available Sulfonamides have been the center of drug structures as this group is quite stable & well tolerated in human beings. The synthesis of these structures was started in search of new pharmacological active reagents. These compounds are being tested for the desired activity (ICAM-1/LFA-1 Interaction inhibitors as anti-adhesion therapeutic agents, the biological activity & structure activity relationship will be published elsewhere. Synthesis of morpholine moiety from amino group is done by using reagent 2-chloroethanol.

  19. Copper-Promoted Desulfitative N-Arylation of Sulfonamides and Sulfoximines with Sodium Arylsulfinates.

    Science.gov (United States)

    Jiang, Yangji; You, Yaping; Dong, Wanrong; Peng, Zhihong; Zhang, Yingjun; An, Delie

    2017-06-02

    A general and direct N-arylation of sulfonamides and NH-sulfoximines by sodium arylsulfinates through a desulfitative pathway was herein demonstrated. The reaction proceeded with catalytic loadings of Cu(II)-catalysts without any external ligands. And the novel arylation protocol featured for high efficiency (up to 93% yields) and good substituent tolerance (up to 53 examples). Moreover, a plausible reaction mechanism was also discussed.

  20. Regioselective Annulation of Aryl Sulfonamides with Allenes through Cobalt-Promoted C-H Functionalization.

    Science.gov (United States)

    Lan, Tianlong; Wang, Liguo; Rao, Yu

    2017-03-03

    The development of an efficient method for the construction of biologically relevant sultams is described, which represents the first case of cobalt-promoted C-H/N-H functionalization of sulfonamides with allenes. This newly developed annulation reaction demonstrated good functional group tolerance and excellent regioselectivity. Both terminal monosubstituted allenes and internal disubstituted allenes can be employed to give the desired sultams in good yields. This strategy can be successfully used to build a unique sultam library with novel structural diversity.

  1. From Sensors to Silencers: Quinoline- and Benzimidazole-Sulfonamides as Inhibitors for Zinc Proteases

    Science.gov (United States)

    2010-01-01

    Derived from the extensive work in the area of small molecule zinc(II) ion sensors, chelating fragment libraries of quinoline- and benzimidazole-sulfonamides have been prepared and screened against several different zinc(II)-dependent matrix metalloproteinases (MMPs). The fragments show impressive inhibition of these metalloenzymes and preferences for different MMPs based on the nature of the chelating group. The findings show that focused chelator libraries are a powerful strategy for the discovery of lead fragments for metalloprotein inhibition. PMID:20507095

  2. Synthesis and Antibacterial Evaluation of Some Novel Imidazole and Benzimidazole Sulfonamides

    Directory of Open Access Journals (Sweden)

    Aidil Abdul Hamid

    2013-09-01

    Full Text Available Several new substituted sulfonamide compounds were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR, and mass spectroscopy. The antibacterial activities of the synthesized compounds were screened against standard strains of six Gram positive and four Gram negative bacteria using the microbroth dilution assay. Most of the compounds studied showed promising activities against both types of bacteria.

  3. RESIDUES OF TETRACYCLINES, SULFONAMIDES AND TYLOSIN IN JAR HONEY FROM LATIUM REGION DURING 2005-2007

    OpenAIRE

    G. Formato; S Saccares; G Migliore; L. De Santis; L. Lusco; C. Di Muro; P. Pulcini

    2008-01-01

    During 3 years (2005-2007), the IZSLT, and the C.R.A. (ex Sezione di Apicoltura dell’Istituto Sperimentale per la Zoologia Agraria – sede di Roma), analized 165 samples of jar honey, from Latium Region, for melissopalinological, sensorial, chemical and physical analysis. The screening test for tetracyclines and tylosin were performed, respectively, with the Tetrasensor Honey kit and the ELISA kit for tylosin. HPLC-ESI-MSMS was used for sulfonamides and for all the samples that res...

  4. Erythromycin Resistance-Conferring Plasmid pRSB105, Isolated from a Sewage Treatment Plant, Harbors a New Macrolide Resistance Determinant, an Integron-Containing Tn402-Like Element, and a Large Region of Unknown Function▿

    Science.gov (United States)

    Schlüter, A.; Szczepanowski, R.; Kurz, N.; Schneiker, S.; Krahn, I.; Pühler, A.

    2007-01-01

    The erythromycin resistance plasmid pRSB105 was previously isolated from an activated sludge bacterial community of a municipal wastewater treatment plant. Compilation of the complete pRSB105 nucleotide sequence revealed that the plasmid is 57,137 bp in size and has a mean G+C content of 56.66 mol%. The pRSB105 backbone is composed of two different replication and/or partitioning modules and a functional mobilization region encoding the mobilization genes mobCDE and mobBA. The first replicon (Rep1) is nearly identical to the corresponding replication module of the multiresistance plasmid pRSB101 isolated from an unknown activated sludge bacterium. Accordingly, pRSB101 and pRSB105 are sister plasmids belonging to a new plasmid family. The second replicon (Rep2) of pRSB105 was classified as a member of the IncP-6 group. While Rep1 confers replication ability only in γ-proteobacteria, Rep2 extents the host range of the plasmid since it is also functional in the β-proteobacterium Ralstonia eutropha. Plasmid pRSB105 harbors the macrolide resistance genes mel and mph, encoding, respectively, a predicted ABC-type efflux permease and a macrolide-2′-phosphotransferase. Erythromycin resistance is mainly attributed to mel, whereas mph contributes to erythromycin resistance to a lesser extent. The second resistance region, represented by an integron-containing Tn402-like element, includes a β-lactam (oxa10) and a trimethoprim (dfrB2) resistance gene cassette. In addition to antibiotic resistance modules, pRSB105 encodes a functional restriction/modification system and two nonresistance regions of unknown function. The presence of different mobile genetic elements that flank resistance and nonresistance modules on pRSB105 indicates that these elements were involved in acquisition of accessory plasmid modules. Comparative genomics of pRSB105 and related plasmids elucidated that pRSB105 evolved by integration of distinct modules from different plasmid sources, including

  5. Acquired resistance to the 16-membered macrolides tylosin and tilmicosin by Mycoplasma bovis.

    Science.gov (United States)

    Lerner, Uri; Amram, Eytan; Ayling, Roger D; Mikula, Inna; Gerchman, Irena; Harrus, Shimon; Teff, Dina; Yogev, David; Lysnyansky, Inna

    2014-01-31

    The molecular mechanism of acquired resistance to the 16-membered macrolides tylosin (Ty) and tilmicosin (Tm) was investigated in Mycoplasma bovis field isolates. Sequence analysis of domains II and V of the two 23S rRNA alleles and ribosomal proteins L4 and L22 was performed on 54 M. bovis isolates showing different minimal inhibitory concentrations (MIC). The presence of any one of the point mutations G748A, C752T, A2058G, A2059G or A2059C (Escherichia coli numbering) in one or both alleles of the 23S rRNAs was correlated with decreased susceptibility to Ty (8-1024 μg/ml) and to Tm (32 to >256 μg/ml) in 27/27 and 27/31 M. bovis isolates, respectively. Although a single mutation in domain II or V could be sufficient to cause decreased susceptibility to Ty, our data imply that a combination of mutations in two domains is necessary to achieve higher MICs (≥ 128 μg/ml). The influence of a combination of mutations in two domains II and V on enhancement of resistance to Tm was less clear. In addition, the amino acid (aa) substitution L22-Q90H was found in 24/32 representative M. bovis isolates with different MICs, but no correlation with decreased susceptibility to Ty or Tm was identified. Multiple aa substitutions were also identified in the L4 protein, including at positions 185-186 (positions 64 and 65 in E. coli) which are adjacent to the macrolide-binding site. This is the first description of the molecular mechanism of acquired resistance to the 16-membered macrolides in M. bovis. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Detection of genetic mutations associated with macrolide resistance of Mycoplasma pneumoniae

    Directory of Open Access Journals (Sweden)

    Chi Eun Oh

    2010-02-01

    Full Text Available Purpose : The aim of this study was to identify mutations associated with macrolide resistance in Mycoplasma pneumoniae (MP and to establish a cultural method to determine antimicrobial susceptibility. Methods : Nasopharyngeal aspirates (NPAs were collected from 62 children diagnosed with MP pneumonia by a serologic method or polymerase chain reaction. The 23S rRNA and L4 ribosomal protein genes of MP were amplified and sequenced. To identify mutations in these 2 genes, their nucleotide sequences were compared to those of the reference strain M129. MP cultivation was carried out for 32 (28 frozen and 5 refrigerated NPAs and M129 strain using Chanock’s glucose broth and agar plate in a 5% CO2 incubator at 37?#608;and examined at 2-3 day intervals for 6 weeks. Results : Among the 62 specimens, 17 had M144V mutations in ribosomal protein L4. The A2064G mutation was observed in 1 specimen; its 23S rRNA gene was successfully sequenced. Culture for MP was successful from the M129 strain and 2 of the 5 NPAs that were refrigerated for no longer than 3 days. However, MP did not grow from the 28 NPAs that were kept frozen at -80?#608;since 2003. Conclusion : We found the M144V mutation of L4 protein to be common and that of domain V of 23S rRNA gene was relatively rare among MP. Studies on the prevalence of macrolide-resistant MP and the relationship between the mutations of 23S rRNA gene and ribosomal protein L4 will aid in understanding the mechanism of macrolide resistance in MP.

  7. Effect of pH and soil structure on transport of sulfonamide antibiotics in agricultural soils.

    Science.gov (United States)

    Park, Jong Yol; Huwe, Bernd

    2016-06-01

    We investigated the effect of solution pH and soil structure on transport of sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) in combination with batch sorption tests and column experiments. Sorption isotherms properly conformed to Freundlich model, and sorption potential of the antibiotics is as follows; sulfadimethoxine > sulfamethoxazole > sulfamethazine. Decreasing pH values led to increased sorption potential of the antibiotics on soil material in pH range of 4.0-8.0. This likely resulted from abundance of neutral and positive-charged sulfonamides species at low pH, which electrostatically bind to sorption sites on soil surface. Due to destruction of macropore channels, lower hydraulic conductivities of mobile zone were estimated in the disturbed soil columns than in the undisturbed soil columns, and eventually led to lower mobility of the antibiotics in disturbed column. The results suggest that knowledge of soil structure and solution condition is required to predict fate and distribution of sulfonamide antibiotics in environmental matrix. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. A portable electrochemical magnetoimmunosensor for detection of sulfonamide antimicrobials in honey.

    Science.gov (United States)

    Muriano, A; Pinacho, D-G; Chabottaux, V; Diserens, J-M; Granier, B; Stead, S; Sanchez Baeza, F; Pividori, M I; Marco, M-P

    2013-09-01

    A new electrochemical magnetoimmunosensor (EMIS) has been developed for the screening of residues of sulfonamide antimicrobials in honey samples. The immunosensor is able to detect up to ten different sulfonamide congeners at levels below the action points established in some European countries (25 μg kg(-1)) after a hydrolysis step in which the sulfonamides are released from the corresponding conjugates formed in samples of this type. In spite of the complexity of the sample after the hydrolysis procedure, the EMIS could perform quantitative measurements, directly in these samples, without any additional sample cleanup or extraction step. For example, sulfapyridine, used as a reference, can be detected in hydrolyzed honey with a limit of detection (IC90) of 0.1 ± 0.03 μg kg(-1). Considering that the use of antibiotics for bee treatment is prohibited in the European Union, the immunosensor presented here could be an excellent screening tool. Moreover, several samples can be processed in parallel, which facilitates the analysis, reducing the necessity to use more costly confirmatory methods for just screening. As a proof of concept, a set of blind honey samples (spiked and incurred) were analyzed and the results were compared with those obtained by high-performance liquid chromatography-tandem mass spectrometry, demonstrating the potential of the EMIS as a screening tool.

  9. Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1.

    Science.gov (United States)

    Alim, Zuhal; Kilic, Deryanur; Koksal, Zeynep; Beydemir, Sukru; Ozdemir, Hasan

    2017-10-01

    Paraoxonase-1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. Due to the PON1's crucial functions, inhibitors and activators of PON1 must be known for pharmacological applications. In this study, we investigated the in vitro effects of some sulfonamides compounds on human serum PON1 (hPON1). For this aim, we purified the hPON1 from human serum with high specific activity by using simple chromatographic methods, and after the purification processes, we investigated in vitro interactions between the enzyme and some sulfonamides (2-amino-5-methyl-1,3-benzenedisulfonamide, 2-chloro-4-sülfamoilaniline, 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, sulfisomidine, and 5-amino-2-methylbenzenesulfonamide). IC 50 , K i values, and inhibition types were calculated for each sulfonamide. 2-amino-5-methyl-1,3-benzenedisulfonamide and 2-chloro-4-sülfamoilaniline exhibited noncompetitive inhibition effect, whereas 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, and sulfisomidine exhibited mixed type inhibition. On the other hand, 5-amino-2-methylbenzenesulfonamide showed competitive inhibition and so molecular docking studies were performed for this compound in order to assess the probable binding mechanism into the active site of hPON1. © 2017 Wiley Periodicals, Inc.

  10. A molecular mechanics valence force field for sulfonamides derived by ab initio methods

    Energy Technology Data Exchange (ETDEWEB)

    Nicholas, J.B.; Burke, B.J.; Hopfinger, A.J. (Univ. of Illinois, Chicago (United States)); Vance, R.; Martin, E. (DowElanco, Walnut Creek, CA (United States))

    1991-11-28

    Molecular mechanics valence force field parameters for the sulfonamide group, SO[sub 2]NH, have been derived from ab initio calculations at the RHF/6-31G* level of theory. The force field parameters were designed to be used in conjunction with existing parameters from the MM2/MMP2 force field. The new parameters are demonstrated to accurately reproduce the ab initio optimized geometries of four molecules that contain the sulfonamide group. The strategy used in force field parametrization is discussed. The conformational flexibility of the sulfonamide group has been investigated. Calculations at the RHF/6-31G* level reveal the existence of two stable conformers and that interconversion is achieved by nitrogen inversion rather than rotation about the S-N bond. The energetic effects of expanding the basis set to 6-31G** and of including MP2 and MP3 corrections for electron correlation are discussed. The geometries and Mulliken charges for the ab initio optimized structures are also reported.

  11. Structural Basis for the Inhibition of Helicobacter pylori α-Carbonic Anhydrase by Sulfonamides.

    Directory of Open Access Journals (Sweden)

    Joyanta K Modak

    Full Text Available Periplasmic α-carbonic anhydrase of Helicobacter pylori (HpαCA, an oncogenic bacterium in the human stomach, is essential for its acclimation to low pH. It catalyses the conversion of carbon dioxide to bicarbonate using Zn(II as the cofactor. In H. pylori, Neisseria spp., Brucella suis and Streptococcus pneumoniae this enzyme is the target for sulfonamide antibacterial agents. We present structural analysis correlated with inhibition data, on the complexes of HpαCA with two pharmacological inhibitors of human carbonic anhydrases, acetazolamide and methazolamide. This analysis reveals that two sulfonamide oxygen atoms of the inhibitors are positioned proximal to the putative location of the oxygens of the CO2 substrate in the Michaelis complex, whilst the zinc-coordinating sulfonamide nitrogen occupies the position of the catalytic water molecule. The structures are consistent with acetazolamide acting as site-directed, nanomolar inhibitors of the enzyme by mimicking its reaction transition state. Additionally, inhibitor binding provides insights into the channel for substrate entry and product exit. This analysis has implications for the structure-based design of inhibitors of bacterial carbonic anhydrases.

  12. Prediction of Physico-chemical Properties of Bacteriostatic N1-Substituted Sulfonamides: Theoretical and Experimental Studies.

    Science.gov (United States)

    Nikoofard, Hossein; Sargolzaei, Mohsen; Faridbod, Farnosh

    2017-12-01

    A computational study at the density functional theory (DFT) as well as electrochemical methods, was carried out on the structural and physico-chemical properties of a series of sulfonamide derivatives (SAs) as WHO essential medications in the treatment of basic health system. The B3LYP/6-311++G(d,p) level of theory carried out on sulfadiazine (SDZ), sulfathiazole (STZ), sulfaquinoxaline (SQX), sulfacetamide (SAA), and the reference unsubstituted sulfonamide (SA) was discussed and rationalized in term of the N1-sulfonamide substituent. The geometric structures and the electronic properties related to the bacteriostatic reactivity were revealed to be affected by the steric and "push-pull" characteristics of the substituents. Electrochemical experiments on oxidation of SAs, using cyclic voltammetry are presented. The results obtained showed that the calculated ionization potentials (IPs) could be correlated linearly with the electro-oxidation potentials. From the molecules studied it is evident that SDZ act as the most electro-active agent, possessing the highest biological activity. DFT computations carried out using the standard molar enthalpies of formation in the gas phase predicted improvements in the thermodynamic stabilization of the SDZ, SQX, and SAA molecules and an unstabilization of STZ with respect to the parent molecule SA.

  13. Carbonic anhydrase inhibitory properties of phenolic sulfonamides derived from dopamine related compounds

    Directory of Open Access Journals (Sweden)

    Hulya Göcer

    2017-03-01

    Full Text Available The effects of some phenolic sulfonamides were determined on the cytosolic carbonic anhydrase isoenzyme I and II (hCA I and II. Both isoenzymes were purified separately from human erythrocytes, using the Sepharose-4B-l-tyrosine-sulfanilamide affinity column chromatography method. In continuation of the study, we identified the inhibitory effects of phenolic sulfonamides 1–4 on the esterase activity of hCA I, and II. The inhibitory effects of phenolic sulfonamides 1–4 were tested on human carbonic anhydrase isoenzymes hCA I, and II. Among the compounds 1–4, compound 1 was concluded to show the best inhibitory effects. According to our data, IC50 values of compound 1 were found as 3.55 and 2.94 μM for hCA I, and hCA II, respectively. On the other hand, Ki values of this compound were found as 0.827 and 0.745 μM for both isoenzymes, respectively.

  14. Determination of Sulfonamides in Chicken Muscle by Pulsed Direct Current Electrospray Ionization Tandem Mass Spectrometry.

    Science.gov (United States)

    Fu, Xian; Liang, Hengxing; Xia, Bing; Huang, Chunyan; Ji, Baocheng; Zhou, Yan

    2017-09-20

    A simple and rapid approach for the simultaneous detection of trace amounts of six sulfonamides in chicken muscle was developed using pulsed direct current electrospray ionization tandem mass spectrometry (pulsed-dc ESI-MS/MS). The pretreatment of chicken muscle samples consisted of two steps: acetonitrile extraction and n-hexane delipidation. Sulfonamides do not need to be derivatized or chromatographed prior to pulsed-dc ESI-MS/MS. The factors affecting the performance of pulsed-dc ESI-MS/MS were studied. Under optimum conditions, the quantitative performance of pulsed-dc ESI-MS/MS was validated according to European Union Decision 2002/657/EC, and the sensitivity of pulsed-dc ESI-MS/MS was 3 times higher than that of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The limits of detection obtained by pulsed-dc ESI-MS/MS were in the range of 0.07-0.11 μg/kg. The proposed method was simple, rapid, and sensitive, and was successfully used for quantitation and rapid screening of sulfonamides in real chicken muscle samples.

  15. Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole

    DEFF Research Database (Denmark)

    Khalil, Insaf; Rønn, Anita M; Alifrangis, Michael

    2003-01-01

    A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genotypes were determined. dhfr genotypes correlated with ...... the cultures....

  16. CONFLEX/MM3 search/minimization study of the conformations of the macrolide antibiotic tylosin

    Science.gov (United States)

    Ivanov, Petko M.

    2002-03-01

    The conformations of the 16-membered macrolide antibiotic tylosin were studied with the MM3 force field. The CONFLEX conformational search procedure was used for finding low-energy conformations. The computed data are indicative for the existence of several conformations in equilibrium. The intramolecular hydrogen bonds play an important role for the preferred geometry of the macroring and the conformations of the side chains. The present results provide further insight into the most probable conformations of tylosin and compliment an earlier analysis based on NMR techniques.

  17. Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

    Directory of Open Access Journals (Sweden)

    Kohei Kawa

    2011-06-01

    Full Text Available b-Hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.

  18. Polymorphism in R-tamsulosin (an alpha blocker): The unexpected manifestation of a sulfonamide⋯o-diethoxybenzene heterosynthon

    Science.gov (United States)

    Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Ravikumar, Krishnan

    2014-12-01

    A two point Nsbnd H⋯O dimer or an infinite catemer are the most preferred motifs/synthons for sulfonamide structures. Such synthons are known to be so robust that they are only disrupted in the presence of highly activated O acceptors such as pyridine-N-oxide and sulfoxide. We demonstrate in this article that a multi-point synthon offered by much weaker ethoxy O and amine N acceptors can however strongly compete and disrupt the robust sulfonamide homosynthons. This has been illustrated with the synthon analysis in three polymorphic crystal structures of R-tamsulosin, an active drug used in the treatment of Benign Prostatic Hyperplasia (BPH) and its hydrochloride salt. These crystalline solids are characterized by Single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR) and Raman spectroscopy. Forms I, II of the free base and hydrochloride salt crystallize in the monoclinic P21, C2, and P21 space groups respectively with two molecules in the asymmetric unit (Z‧ = 2), whereas, form III of freebase crystallize in the orthorhombic P212121 space group with Z‧ = 1. Remarkably, all four crystal structures contain a totally unexpected sulfonamide⋯o-diethoxybenzene heterosynthon. The multi-point motifs observed in polymorphs are relatively stronger than those in the hydrochloride salt because of the gauche conformation of the tamsulosin linker chain which renders an additional hydrogen bond interaction with amine N acceptor, and resemble the crown ether sulfonamide recognition pattern. Observation of this new heterosynthon offers potential scope in the design of pharmaceutical cocrystals for sulfonamide bearing drug molecules. The present study also presents a detailed hydrogen bond motif analysis in 310 primary sulfonamide structures culled from the latest version of Cambridge Structural Database (CSD). The role of various competing groups is discussed in the context of understanding the most recurring

  19. The first reported case of concurrent trimethoprim-sulfamethoxazole-induced immune hemolytic anemia and thrombocytopenia.

    Science.gov (United States)

    Linnik, Yevgeniy A; Tsui, Edison W; Martin, Isabella W; Szczepiorkowski, Zbigniew M; Denomme, Gregory A; Gottschall, Jerome L; Hill, John M; Dunbar, Nancy M

    2017-12-01

    Drug-induced immune hemolytic anemia (DIIHA) and drug-induced immune thrombocytopenia (DIIT) are rare but dangerous complications of pharmacotherapy that may be underrecognized in hematopoietic stem cell transplant (HSCT) patients due to overlap of signs and symptoms with those of more common disease processes. A 61-year-old woman with NK-cell deficiency and GATA-2-associated myelodysplastic syndrome, status post-recent allogeneic HSCT (Day +58), presented with 3 days of acute-onset severe back pain, muscle cramps, and increasingly dark urine. She was found to be anemic, thrombocytopenic, and in acute renal failure. On admission, the direct antiglobulin test was positive for complement (C3) only. After careful review of her medication list, the possibility of DIIHA was raised. She had started taking trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jiroveci pneumonia prophylaxis 24 days prior on a weekend dose schedule. Serologic tests on peripheral blood samples were performed using standard methods. Drug studies were performed at an immunohematology reference laboratory. The patient's serum showed hemolysis of donor red blood cells in the presence of TMP-SMX and also TMP-SMX-induced platelet antibodies. The patient was treated with transfusions, hemodialysis, and immunosuppressive agents. Her clinical condition improved and she was discharged after 8 days in stable condition. This case describes the first reported concurrent DIIHA and DIIT due to TMP-SMX-induced antibodies in an HSCT patient. DIIHA and DIIT can present a diagnostic challenge in the setting of intermittent medication dosing. © 2017 AABB.

  20. Reaction of some macrolide antibiotics with the ribosome. Labeling of the binding site components

    International Nuclear Information System (INIS)

    Tejedor, F.; Ballesta, J.P.

    1986-01-01

    Radioactive carbomycin A, niddamycin, tylosin, and spiramycin, but not erythromycin, can be covalently bound to Escherichia coli ribosomes by incubation at 37 degrees C. The incorporation of radioactivity into the particles is inhibited by SH- and activated double bond containing compounds but not by amino groups, suggesting that the reactions may take place by addition to the double bond present in the reactive antibiotics. This thermic reaction must be different from the photoreaction described for some of these macrolides [Tejedor, F., and Ballesta, J. P. G. (1985) Biochemistry 24, 467-472] since tylosin, which is not photoincorporated, is thermically bound to ribosomes. Most of the radioactivity is incorporated into the ribosomal proteins. Two-dimensional gel electrophoresis of proteins labeled by carbomycin A, niddamycin, and tylosin indicates that about 40% of the radioactivity is bound to protein L27; the rest is distributed among several other proteins such as L8, L2, and S12, to differing extents depending on the drug used. These results indicate, in accordance with previous data, that protein L27 plays an important role in the macrolide binding site, confirming that these drugs bind near the peptidyl transferase center of the ribosome

  1. Reaction of some macrolide antibiotics with the ribosome. Labeling of the binding site components

    Energy Technology Data Exchange (ETDEWEB)

    Tejedor, F.; Ballesta, J.P.

    1986-11-18

    Radioactive carbomycin A, niddamycin, tylosin, and spiramycin, but not erythromycin, can be covalently bound to Escherichia coli ribosomes by incubation at 37 degrees C. The incorporation of radioactivity into the particles is inhibited by SH- and activated double bond containing compounds but not by amino groups, suggesting that the reactions may take place by addition to the double bond present in the reactive antibiotics. This thermic reaction must be different from the photoreaction described for some of these macrolides (Tejedor, F., and Ballesta, J. P. G. (1985) Biochemistry 24, 467-472) since tylosin, which is not photoincorporated, is thermically bound to ribosomes. Most of the radioactivity is incorporated into the ribosomal proteins. Two-dimensional gel electrophoresis of proteins labeled by carbomycin A, niddamycin, and tylosin indicates that about 40% of the radioactivity is bound to protein L27; the rest is distributed among several other proteins such as L8, L2, and S12, to differing extents depending on the drug used. These results indicate, in accordance with previous data, that protein L27 plays an important role in the macrolide binding site, confirming that these drugs bind near the peptidyl transferase center of the ribosome.

  2. Synergy of four macrolide antibiotics with chloroquine against chloroquine-resistant Plasmodium falciparum in vitro.

    Science.gov (United States)

    Gershon, P; Howells, R E

    1986-01-01

    The antimalarial activity of four macrolide antibiotics was investigated against the multidrug resistant K1 strain of Plasmodium falciparum in vitro. ID50 (50% inhibitory concentration) values for erythromycin, spiramycin, tylosin tartrate and oleandomycin phosphate in 48-hour assays were 1.6 X 10(-4)M, 2.5 X 10(-5)M, 1.2 X 10(-5)M and 9 X 10(-6)M respectively, and in 96 hour assays were 10(-5)M, 2.6 X 10(-6)M, 2.6 X 10(-6) and 3 X 10(-6)M, respectively. Comparable values were obtained in assays in which drug effect was quantified from either parasite counts or 14C isoleucine incorporation. Each of the four macrolides displayed synergy with chloroquine at the IC90 (90% inhibitory concentration) level, but at the IC50 level synergy was either less pronounced or absent. For each combination this difference in the degree of synergy was significant at the 95% level of confidence. In replicate assays in which 3H hypoxanthine was the marker of drug effect, synergy between chloroquine and either erythromycin or spiramycin could not be detected.

  3. Hydrolysis of amphenicol and macrolide antibiotics: Chloramphenicol, florfenicol, spiramycin, and tylosin.

    Science.gov (United States)

    Mitchell, Shannon M; Ullman, Jeffrey L; Teel, Amy L; Watts, Richard J

    2015-09-01

    Antibiotics that enter the environment can present human and ecological health risks. An understanding of antibiotic hydrolysis rates is important for predicting their environmental persistence as biologically active contaminants. In this study, hydrolysis rates and Arrhenius constants were determined as a function of pH and temperature for two amphenicol (chloramphenicol and florfenicol) and two macrolide (spiramycin and tylosin) antibiotics. Antibiotic hydrolysis rates in pH 4-9 buffer solutions at 25°C, 50°C, and 60°C were quantified, and degradation products were characterized. All of the antibiotics tested remained stable and exhibited no observable hydrolysis under ambient conditions typical of aquatic ecosystems. Acid- and base-catalyzed hydrolysis occurred at elevated temperatures (50-60°C), and hydrolysis rates increased considerably below pH 5 and above pH 8. Hydrolysis rates also increased approximately 1.5- to 2.9-fold for each 10°C increase in temperature. Based on the degradation product masses found, the functional groups that underwent hydrolysis were alkyl fluoride, amide, and cyclic ester (lactone) moieties; some of the resultant degradation products may remain bioactive, but to a lesser extent than the parent compounds. The results of this research demonstrate that amphenicol and macrolide antibiotics persist in aquatic systems under ambient temperature and pH conditions typical of natural waters. Thus, these antibiotics may present a risk in aquatic ecosystems depending on the concentration present. Copyright © 2015. Published by Elsevier Ltd.

  4. Multi-residue fluorescent microspheres immunochromatographic assay for simultaneous determination of macrolides in raw milk.

    Science.gov (United States)

    Li, Xiangmei; Shen, Jianzhong; Wang, Qi; Gao, Shuxia; Pei, Xingyao; Jiang, Haiyang; Wen, Kai

    2015-12-01

    A rapid, reliable, sensitive, and quantitative multi-residue fluorescent microspheres immunochromatographic assay (FMCA) was developed for simultaneous detection of four macrolides in raw milk. The IC50 value of the optimized FMCA was 1.36, 1.22, 1.01, and 1.39 ng/mL for erythromycin (ERY), spiramycin (SPI), tilmicosin (TIM), and tylosin (TYL), respectively. The limits of detection (LODs) for the four macrolides was 0.13 ng/mL. The recoveries of ERY, SPI, TIM, and TYL from spiked raw milk ranged from 91.8-109.2, 89.6-114.4, 84.8-111.6, and 85.8-115.2%, respectively, with coefficients of variation (CVs) of 5.4-11.3, 7.9-15.7, 6.2-13.7, and 3.2-14.9%, respectively. The whole testing process was completed within 20 min. The antibody-mixed labeled method was successfully applied to the FMCA, which greatly simplified the operation steps and saved a lot of time. Compared with the immunogold chromatographic assay (IGCA), the FMCA is more sensitive and stable and has less antibody consumption. A parallel analysis in blind raw milk samples was conducted by liquid chromatography-tandem mass spectrometry (LC-MS/MS); the results showed good correlation (r(2) = 0.99) between the two methods. Therefore, the developed multi-residue FMCA is reliable and can be easily applied to other antibiotics or other contaminants.

  5. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    Directory of Open Access Journals (Sweden)

    Euna eOh

    2015-10-01

    Full Text Available The increasing resistance of Campylobacter to clinically-important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN. Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux.

  6. Sulfonamides identified as plant immune-priming compounds in high-throughput chemical screening increase disease resistance in Arabidopsis thaliana.

    Science.gov (United States)

    Noutoshi, Yoshiteru; Ikeda, Mika; Saito, Tamio; Osada, Hiroyuki; Shirasu, Ken

    2012-01-01

    Plant activators are agrochemicals that protect crops from diseases by activating the plant immune system. To isolate lead compounds for use as practical plant activators, we screened two different chemical libraries composed of various bioactive substances by using an established screening procedure that can selectively identify immune-priming compounds. We identified and characterized a group of sulfonamide compounds - sulfameter, sulfamethoxypyridazine, sulfabenzamide, and sulfachloropyridazine - among the various isolated candidate molecules. These sulfonamide compounds enhanced the avirulent Pseudomonas-induced cell death of Arabidopsis suspension cell cultures and increased disease resistance in Arabidopsis plants against both avirulent and virulent strains of the bacterium. These compounds did not prevent the growth of pathogenic bacteria in minimal liquid media at 200 μM. They also did not induce the expression of defense-related genes in Arabidopsis seedlings, at least not at 24 and 48 h after treatment, suggesting that they do not act as salicylic acid analogs. In addition, although sulfonamides are known to be folate biosynthesis inhibitors, the application of folate did not restore the potentiation effects of the sulfonamides on pathogen-induced cell death. Our data suggest that sulfonamides potentiate Arabidopsis disease resistance by their novel chemical properties.

  7. Sulfonamides identified as plant immune-priming compounds in high-throughput chemical screening increase disease resistance in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Yoshiteru eNoutoshi

    2012-10-01

    Full Text Available Plant activators are agrochemicals that protect crops from diseases by activating the plant immune system. To isolate lead compounds for use as practical plant activators, we screened 2 different chemical libraries composed of various bioactive substances by using an established screening procedure that can selectively identify immune-priming compounds. We identified and characterized a group of sulfonamide compounds—sulfameter, sulfamethoxypyridazine, sulfabenzamide, and sulfachloropyridazine—among the various isolated candidate molecules. These sulfonamide compounds enhanced the avirulent Pseudomonas-induced cell death of Arabidopsis suspension cell cultures and increased disease resistance in Arabidopsis plants against both avirulent and virulent strains of the bacterium. These compounds did not prevent the growth of pathogenic bacteria in minimal liquid media at 200 µM. They also did not induce the expression of defense-related genes in Arabidopsis seedlings, at least not at 24 and 48 h after treatment, suggesting that they do not act as salicylic acid analogs. In addition, although sulfonamides are known to be folate biosynthesis inhibitors, the application of folate did not restore the potentiation effects of the sulfonamides on pathogen-induced cell death. Our data suggest that sulfonamides potentiate Arabidopsis disease resistance by their novel chemical properties.

  8. Synthesis of thiazolidine-thiones, imino-thiazolidines and oxazolidines via the base promoted cyclisation of epoxy-sulfonamides and heterocumulenes.

    Science.gov (United States)

    Anitha, Mandala; Swamy, K C Kumara

    2018-01-17

    Epoxy-sulfonamides react with heterocumulenes (carbon disulfide/isothiocyanates/isocyanates) in the presence of a base to afford ring expansion products in good to high yields with excellent regioselectivity. N-(2-Bromoethyl)-sulfonamides can also be employed as substrates. This reaction proceeds through a 5-exo-tet pathway without forming aziridine intermediates.

  9. Macrolide use and the risk of vascular disease in HIV-infected men in the Multicenter AIDS Cohort Study

    DEFF Research Database (Denmark)

    Woolley, Ian J; Li, Xiuhong; Jacobson, Lisa P

    2007-01-01

    of macrolide prophylaxis on those outcomes. METHODS: A subcohort analysis was undertaken using data collected in the Multicenter AIDS Cohort Study to examine the relative risk of vascular events (myocardial infarction, unstable angina and ischaemic stroke). Cox proportional hazard model using age as the time...

  10. Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

    Directory of Open Access Journals (Sweden)

    Lutz Larissa

    2012-09-01

    Full Text Available Abstract Background Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF patients. Results A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P P = 0.005. When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P  0.001 and tobramycin (P  0.001, regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions. Conclusions P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.

  11. Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis

    NARCIS (Netherlands)

    S.J. Phaff (Sonja); H.A.W.M. Tiddens (Harm); H.A. Verbrugh (Henri); A. Ott (Alewijn)

    2006-01-01

    textabstractOBJECTIVES: Azithromycin is used to modulate exuberant inflammatory response in patients with cystic fibrosis (CF). The purpose of this study was to determine the association between long-term use of azithromycin in CF patients and change over time in macrolide susceptibility of

  12. Genome-wide identification and characterization of macrolide glycosyltransferases from a marine-derived Bacillus strain and their phylogenetic distribution.

    Science.gov (United States)

    Liu, Yang; Qin, Wen; Liu, Quanquan; Zhang, Jun; Li, Huayue; Xu, Shanshan; Ren, Pengfei; Tian, Li; Li, Wenli

    2016-12-01

    Clarifying glycosyltrasferases (GTs) function is of significance for the development of GT inhibitors as drugs, and the use of GTs to glycodiversify small molecules in the search of drug leads. While many Actinomyces natural-product GTs had been functionally characterized, our understanding towards Bacillus natural-product GTs is so far very limited. Herein, genome-wide identification of macrolide GT genes from marine-derived Bacillus methylotrophicus B-9987 revealed the presence of three macrolide GT genes bmmGT1-3. While bmmGT1 was previously revealed to be involved in the biosynthesis of trans-acyltransferase (AT) polyketides compounds macrolactins (MLNs) and bacillaenes (BAEs), the functions of bmmGT2 and bmmGT3 were probed, demonstrating that they are capable to biochemically catalyze glycosylation of MLNs and BAEs as well but interestingly with different regioselectivity, affording four new MLNs analogs. Notably, further genome mining revealed that the orthologs of these three macrolide GT genes showed a regular distribution in the subtilis- and the cereus-clade Bacillus strains; interestingly, bmmGT1 orthologs only occurred in the subtilis-clade Bacillus, and they were also found in the genomes of Streptomyces strains, suggesting their close phylogenetic relationship. These results provide the first significant insight into the important roles of Bacillus macrolide GTs in the biology of the species. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Molecular mechanisms of quinolone, macrolide, and tetracycline resistance among Campylobacter isolates from initial stages of broiler production.

    Science.gov (United States)

    Pérez-Boto, D; Herrera-León, S; García-Peña, F J; Abad-Moreno, J C; Echeita, M A

    2014-01-01

    The aim of this study was to investigate the resistance mechanisms of quinolones, macrolides and tetracycline in campylobacter isolates from grandparent and parent broiler breeders in Spain. Twenty-six isolates were investigated for quinolone resistance, three isolates for macrolide resistance and 39 for tetracycline resistance. All of the quinolone-resistant isolates possessed the mutation Thr86Ile in the quinolone resistance-determining region of gyrA and one isolate possessed the mutation Pro104Ser. Only one Campylobacter coli population (defined by restriction fragment length polymorphism-polymerase chain reaction of flaA and pulsed field gel electrophoresis) was resistant to erythromycin, and the mutation A2075G (23S rDNA) was responsible for macrolide resistance. The tetO gene was found in all of the tetracycline-resistant isolates. Twenty-two out of the 39 isolates investigated by Southern blot possessed chromosomic location of tetO and 17 were located on plasmids. Most of the plasmids with tetO were of around 60 kb and conjugation was demonstrated in a selection of them. In conclusion, we showed that Thr86Ile is highly prevalent in quinolone-resistant isolates as well as mutation A2075G in macrolide-resistant isolates of poultry origin. More variability was found for tetO. The possibility of horizontal transmission of tetO among campylobacter isolates is also an issue of concern in public health.

  14. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene

    Science.gov (United States)

    Berryman, Orion B.; Johnson, Charles A.; Vonnegut, Chris L.; Fajardo, Kevin A.; Zakharov, Lev N.; Johnson, Darren W.; Haley, Michael M.

    2015-01-01

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)–C(sp2) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2′-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N–H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF4− or HSO4−, where the sulfonamide arms rotate to the side opposite the pyridine N atom. PMID:26405435

  15. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene.

    Science.gov (United States)

    Berryman, Orion B; Johnson, Charles A; Vonnegut, Chris L; Fajardo, Kevin A; Zakharov, Lev N; Johnson, Darren W; Haley, Michael M

    2015-03-04

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)-C(sp 2 ) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2'-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N-H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF 4 - or HSO 4 - , where the sulfonamide arms rotate to the side opposite the pyridine N atom.

  16. DESIGN, SYNTHESIS AND ANTICANCER ACTIVITY OF SOME NOVEL 1,2,4-TRIAZOLES CARRYING BIOLOGICALLY ACTIVE SULFONAMIDE MOIETIES.

    Science.gov (United States)

    Ghorab, Mostafa M; Alsaid, Mansour S; Al-Dosari, Mohammed

    2016-09-01

    Thirteen novel 1, 2, 4-triazoles incorporating a biologically active sulfonamide moieties 1-13 were designed and synthesized. The structures of the prepared compounds were elucidated on the basis of elemental analyses, IR, 'H-NMR, "C-NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vino anticancer activity against various cancer cell lines. The corresponding triazole carrying a biologically active free sulfonamide with unsubstituted phenyl ring 1 and triazole bearing sulfonamide with dimethylpyrimidine 11 were the most potent in this study which showed higher activity than the reference drug 2',7'-dichlorofluorescein (DCF). Cytotoxic screening of the tested compounds could offer an encouraging framework in the field that may lead to the discovery of potent anticancer activity.

  17. Synthesis, structure and physicochemical properties of zinc and copper complexes based on sulfonamides containing 8-aminoquinoline ligands

    Directory of Open Access Journals (Sweden)

    Luiz Everson da Silva

    2008-01-01

    Full Text Available Sulfonamides obtained by reaction of 8-aminoquinoline with 4-nitrobenzenesulfonylchloride and 2,4,6-triisopropylbenzenesulfonyl chloride were used to synthesize coordination compounds with CuII and ZnII with a ML2 composition. Determination of the crystal structures of the resulting zinc and copper complexes by X-ray diffraction show a distorted tetrahedral environment for the [Cu(qnbsa2], [Cu(qibsa2] and [Zn(qibsa2] complexes in which the sulfonamide group acts as a bidentate ligand through the nitrogen atoms from the sulfonamidate and quinoline groups. The complex [Zn(qnbsa2] crystallizes with a water molecule from the solvent and the Zn is five-coordinated and shows a bipyramidal-trigonal geometry. The electrochemical and electronic spectroscopy properties of the copper complexes are also discussed.

  18. Synthesis, structure and physicochemical properties of zinc and copper complexes based on sulfonamides containing 8-aminoquinoline ligands

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Luiz Everson da; Sousa Junior, Paulo Teixeira de [Universidade Federal de Mato Grosso (UFMT), Cuiaba, MT (Brazil). Dept. de Quimica; Joussef, Antonio Carlos; Piovezan, Clovis; Neves, Ademir [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Quimica]. E-mail: ademir@qmc.ufsc.br

    2008-07-01

    Sulfonamides obtained by reaction of 8-aminoquinoline with 4-nitrobenzenesulfonylchloride and 2,4,6-triisopropylbenzenesulfonyl chloride were used to synthesize coordination compounds with Cu{sup II} and Zn{sup II} with a ML{sub 2} composition. Determination of the crystal structures of the resulting zinc and copper complexes by X-ray diffraction show a distorted tetrahedral environment for the [Cu(qnbsa){sub 2}], [Cu(qibsa){sub 2}] and [Zn(qibsa){sub 2}] complexes in which the sulfonamide group acts as a bidentate ligand through the nitrogen atoms from the sulfonamidate and quinoline groups. The complex [Zn(qnbsa){sub 2}] crystallizes with a water molecule from the solvent and the Zn is five-coordinated and shows a bipyramidal-trigonal geometry. The electrochemical and electronic spectroscopy properties of the copper complexes are also discussed. (author)

  19. In vitro impact of macrolide antibiotics on the viability of selected mammalian cell lines

    Directory of Open Access Journals (Sweden)

    Eva Tvrdá

    2016-10-01

    Full Text Available The aim of this study was to evaluate the in vitro cytotoxicity of different concentrations of macrolide  antibiotics (tilmicosin-TILM, tylosin-TYL and spiramycin-SPI on selected animal cell cultures. VERO cells (kidney cells from Macacus rhesus, FE cells (feline embryonal cells and BHK 21 cells (cell line from young hamster kidneys were used in the study and subjected to concentrations of macrolides ranging 50-1000 µg/mL, depending on the specific antibiotic and cell line. The cell viability expressed as the mitochondrial activity of living cells was assessed using the metabolic mitochondrial MTT test. The effect of tilmicosin: FE cells were the most sensitive with a significant decrease of mitochondrial activity at 100-150 µg/mL (P<0.001 TILM. VERO cells were the most resistant, as no significant decrease of viability was observed at any TILM dose. The effect of tylosin: FE cells showed the highest sensitivity to TYL, as 1000 µg/mL reduced the cell viability to a half (P<0.001 when compared to the untreated control. Similarly, a decreased viability of BHK 21 cells was observed following the supplementation of 1500 (P<0.001 and 900 (P<0.05 µg/mL TYL. VERO cells exhibited the highest resilience to the TYL treatment, with no significant differences of viability in comparison to the control. The effect of spiramycin: BHK 21 cells exhibited the highest sensitivity to the antibiotic, as all concentrations (150, 200, 300 µg/mL SPI led to a significant decrease (P<0.001 of the mitochondrial activity.  Similarly, the viability of FE cells significantly (P<0.05 decreased after the administration of 350 and 540 µg/mL SPI. On the other hand, VERO cells revealed the highest resistance to the antibiotic, with no significant effects in comparison to the control. Our data reveal that macrolides have a significant adverse negative effect on the cell viability, and may provide more information to our knowledge on the specific effects medication has on

  20. Tetracycline and trimethoprim/sulfamethoxazole at clinical laboratory: can they help to characterize Staphylococcus aureus carrying different SCCmec types?

    Science.gov (United States)

    Cavalcante, Fernanda Sampaio; Schuenck, Ricardo Pinto; Caboclo, Roberta Mello Ferreira; Ferreira, Dennis de Carvalho; Nouér, Simone Aranha; Santos, Kátia Regina Netto dos

    2013-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) can be difficult to detect at the clinical practice. We analyzed 140 MRSA isolates from inpatients to correlate the antimicrobial susceptibility with the SCCmec types. Type III (n = 63) isolates were more resistant to ciprofloxacin, clindamycin, cloramphenicol, erythromycin, gentamicin, and rifampin than type IV (n = 65) ones (p < 0.05). Moreover, type IV isolates were susceptible to tetracycline (100%) and trimethoprim/sulfamethoxazole (98%), while type III isolates presented resistance to them. In regions where these SCCmec types are prevalent, the detection of specific resistant phenotypes could help to predict them, mainly when there are no technical conditions to SCCmec typing.

  1. Concentrations of trimethoprim and sulfamethoxazole in cerebrospinal fluid and serum in mares with and without a dimethyl sulfoxide pretreatment.

    OpenAIRE

    Green, S L; Mayhew, I G; Brown, M P; Gronwall, R R; Montieth, G

    1990-01-01

    Each of seven mares was given an intravenous (IV) injection of 40% dimethyl sulfoxide (DMSO) at a dosage of 1 g/kg, over 35 min, immediately followed by a single IV injection of a trimethoprim (TMP) and sulfamethoxazole (SMZ) combination (SMZ 83%, TMP 17%) at a combined dosage of 44 mg/kg (7.48 mg/kg TMP; 36.52 mg/kg SMZ). Each horse served as its own control and was alternately treated with an identical dose of TMP-SMZ treatment alone at least seven days following or preceding the DMSO and T...

  2. Adsorption of sulfonamides to demineralized pine wood biochars prepared under different thermochemical conditions

    International Nuclear Information System (INIS)

    Xie, Mengxing; Chen, Wei; Xu, Zhaoyi; Zheng, Shourong; Zhu, Dongqiang

    2014-01-01

    The main objective of this study was to understand the key factors and mechanisms controlling adsorption of sulfonamides to biochars. Batch adsorption experiments were performed for sulfamethoxazole and sulfapyridine to three pine-wood biochars prepared under different thermochemical conditions: pyrolysis at 400 °C (C400) and 500 °C (C500), and pyrolysis at 500 °C followed with hydrogenation (C500-H). For both sulfonamides, the adsorbent surface area-normalized adsorption was stronger to C500 than to C400. This is attributable to the enhanced π–π electron-donor–acceptor interaction with the carbon surface of C500 due to the higher degree of graphitization. Despite the relatively large difference in surface O-functionality content between C500 (12.2%) and C500-H (6.6%), the two biochars exhibited nearly identical adsorbent surface area-normalized adsorption, indicating negligible role of surface O-functionalities in the adsorption to these adsorbents. Effects of solution chemistry conditions (pH, Cu 2+ , and dissolved soil humic acid) on adsorption were examined. -- Highlights: • Adsorption to biochars is dominated by π–π electron-donor–acceptor (EDA) interaction. • Graphitic surfaces of biochars are predominant adsorption sites. • Surface O-functionalities of biochars play minor roles in adsorption. • Adsorption affinities are markedly affected by Cu ions and humic acids. -- Adsorption of sulfonamides to biochars is dominated by π–π electron-donor–acceptor (EDA) interaction with the graphitic surface

  3. Thermodynamic aspects of solubility and partitioning processes of some sulfonamides in the solvents modeling biological media

    International Nuclear Information System (INIS)

    Perlovich, German L.; Ryzhakov, Alex M.; Strakhova, Nadezda N.; Kazachenko, Vladimir P.; Schaper, Klaus-Jürgen; Raevsky, Oleg A.

    2014-01-01

    Highlights: • Solubility processes of some sulfonamide isomers in water and 1-octanol were investigated. • Transfer processes from water to 1-octanol were evaluated by analysis of enthalpic and entropic terms. • Impact of various substituents in phenyl rings on solubility and transfer processes was studied. -- Abstract: The thermodynamic aspects of solubility processes of sulfonamides (SAs) with the general structures 4-NH 2 –C 6 H 4 –SO 2 NH–C 6 H 2 (R 1 )(R 2 )-R 3 (R 1 = 2-CH 3 , 2-Cl; R 2 = 4-CH 3 , 4-Cl; R 3 =5-H, 5-Cl), 4-NH 2 -2-Cl–C 6 H 3 –SO 2 NH–C 6 H 3 (R 1 )-R 2 (R 1 = 2-H, 2-Cl; R 2 = 4-H, 4-Cl) and 4-NH 2 -2-CH 3 –C 6 H 3 –SO 2 NH–C 6 H 3 (R 1 )-R 2 (R 1 = 2-H, 2-Cl, 2-NO 2 ; R 2 = 4-H, 4-Cl) in water and 1-octanol (as phases modeling various drug delivery pathways) were studied using the isothermal saturation method. For the sulfonamides with various substituents in phenyl rings the processes of transfer from water to 1-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight that the contribution of these terms is different for different molecules (entropy- or enthalpy-determined). Thus, in contrast to the interpretation of only the Gibbs energy of transfer (extensively used for pharmaceuticals in the form of the partition coefficient, logP), the analysis of thermodynamic functions of the transfer process provides additional mechanistic information. This may be important for further evaluation of the physiological distribution of drug molecules and may provide a better understanding of biopharmaceutical properties of drugs

  4. Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

    Directory of Open Access Journals (Sweden)

    Bekdemir Yunus

    2008-08-01

    Full Text Available Abstract Background Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance. Methods Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested. Results The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably. Conclusion This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.

  5. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62,993), and A-56268) on Toxoplasma gondii

    Energy Technology Data Exchange (ETDEWEB)

    Chang, H.R.; Pechere, J.C.

    1988-04-01

    The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with (/sup 3/H)uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

  6. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Pettigrew, Melinda M.; Tsuji, Brian T.; Gent, Janneane F.; Kong, Yong; Holden, Patricia N.; Sethi, Sanjay

    2016-01-01

    Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 μg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance. PMID:27139476

  7. Development of an analytical method for determination of sulfonamide residues in eggs

    International Nuclear Information System (INIS)

    Ben Azzeddine, Chams

    2009-01-01

    For the determination of sulfonamide residues in eggs, Premitest is selected for screening, providing a qualitative biological approach, it is inexpensive, fast, multi-elements and easy to implement. The H. P.L.C. / UV is the quantitative method of choice for confirmation and determination of these contaminants. During my internship, I had the opportunity to participate in the development of this method. It is recognized slower and more expensive but more specific and more sensitive. In this report, I present this optimized method and some criteria checked during my internship. Other criteria are to be completed to validate the method that will be subsequently used for routine analysis.

  8. Bismuth(III) triflate promoted intramolecular hydroamination of unactivated alkenyl sulfonamides in the preparation of pyrrolidines.

    Science.gov (United States)

    Mathia, František; Szolcsányi, Peter

    2012-04-14

    Bi(OTf)(3)·nH(2)O was found to be an efficient promoter of the cyclisative hydroamination of unactivated alkenyl sulfonamides, giving rise to the N-protected 2-methyl pyrrolidines in good to excellent yields (up to 95%). Based on control experiments, a joint Lewis acid-Brønsted acid catalysis might be in operation, or triflic acid itself, generated in situ by hydrolysis of metal triflate, could be the true hydroamination catalyst. This journal is © The Royal Society of Chemistry 2012

  9. 4-Methyl-N-(1-methyl-1H-indazol-5-yl)benzene­sulfonamide

    Science.gov (United States)

    Chicha, Hakima; Oulemda, Bassou; Rakib, El Mostapha; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    In the title compound, C15H15N3O2S, the fused ring system is close to planar, the largest deviation from the mean plane being 0.030 (2) Å, and makes a dihedral angle of 48.84 (9)° with the benzene ring belonging to the methyl­benzene­sulfonamide moiety. In the crystal, mol­ecules are ­connected through N—H⋯N hydrogen bonds and weak C—H⋯O contacts, forming a two-dimensional network parallel to (001). PMID:24427093

  10. Synthesis of Sulfonamides and Evaluation of Their Histone Deacetylase (HDAC Activity

    Directory of Open Access Journals (Sweden)

    Jae–Chul Jung

    2007-05-01

    Full Text Available A simple synthesis of sulfonamides 4–22 as novel histone deacetylase (HDAC inhibitors is described. The key synthetic strategies involve N–sulfonylation of L–proline benzyl ester hydrochloride (2 and coupling reaction of N–sulfonyl chloride 3 with amines in high yields. It was found that several compounds showed good cellular potency with the most potent compound 20 exhibiting an IC50 = 2.8 μM in vitro.

  11. Synthesis of Sulfones and Sulfonamides via Sulfinate Anions: Revisiting the Utility of Thiosulfonates.

    Science.gov (United States)

    Shyam, Pranab K; Jang, Hye-Young

    2017-02-03

    Simple and high-yielding strategies for the production of a variety of sulfones and sulfonamides, using thiosulfonates synthesized by copper-catalyzed aerobic dimerization, are reported. Although thiosulfonates are an old class of compound, practical methods for their synthesis and utilization have not been rigorously developed. In this study, we revisit the reactions of easily accessible thiosulfonates to form sulfinate anions. Because of the similar reactivity of thiosulfonates and metal sulfinates derived from toxic SO 2 , thiosulfinates are proposed to be stable, nontoxic alternatives to metal sulfinate salts.

  12. Investigation of the fate of sulfonamides downgradient of a decommissioned sewage farm near Berlin, Germany

    Science.gov (United States)

    Richter, Doreen; Massmann, Gudrun; Taute, Thomas; Duennbier, Uwe

    2009-05-01

    The drinking water production of a drinking water treatment plant in Berlin is affected by ambient contaminated groundwater. The three organic compounds para-toluenesulfonamide (p-TSA), ortho-toluenesulfonamide (o-TSA) and benzenesulfonamide (BSA) were identified in the catchment area of this plant. The groundwater pollution is a result of former sewage farm irrigation in the area, operating for almost 70 years until the 1980s. The distribution of the sulfonamides in the anoxic groundwater was investigated, and a large number of observation and production wells were sampled for this purpose. The contaminant plume is 25 m * 3000 m * 2000 m (depth, length, width) in size. The high concentrations of p-TSA, o-TSA and BSA in the groundwater show that the sulfonamides persist over decades in an anoxic aquifer environment. Groundwater quality assessment revealed that elevated concentrations of the analytes can be expected in the abstraction well galleries in the future. Therefore, sulfonamides should periodically be monitored in the drinking water (maximum allowed concentration of 0.30 µg/L of p-TSA and for o-TSA and BSA, a limit of 0.10 µg/L for unknown substances applies). Because of the widespread application and the persistence of the sulfonamides under anoxic conditions, our local investigations suggest that the substances may generally be present in groundwater under the influence of sewage irrigation. Incubation experiments were conducted under in situ hydrostatic pressure to study the behaviour of these trace organic compounds under different redox conditions (oxic and anoxic). Groundwater sampling equipment was either sterilised or not sterilised in order to distinguish between microbiological processes occurring in the aquifer and those representing sampling and storage artefacts (incubation experiments). Results showed that the addition of oxygen to the anoxic groundwater facilitates p-TSA and o-TSA degradation. Hence, while the substances are persistent

  13. Discovery of morpholine-based aryl sulfonamides as Nav1.7 inhibitors.

    Science.gov (United States)

    Wu, Yong-Jin; Guernon, Jason; McClure, Andrea; Venables, Brian; Rajamani, Ramkumar; Robbins, Kevin J; Knox, Ronald J; Matchett, Michele; Pieschl, Rick L; Herrington, James; Bristow, Linda J; Meanwell, Nicholas A; Olson, Richard; Thompson, Lorin A; Dzierba, Carolyn

    2018-03-01

    Replacement of the piperidine ring in the lead benzenesulfonamide Na v 1.7 inhibitor 1 with a weakly basic morpholine core resulted in a significant reduction in Na v 1.7 inhibitory activity, but the activity was restored by shortening the linkage from methyleneoxy to oxygen. These efforts led to a series of morpholine-based aryl sulfonamides as isoform-selective Na v 1.7 inhibitors. This report describes the synthesis and SAR of these analogs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Synthesis and characterization of curcumin-sulfonamide hybrids: Biological evaluation and molecular docking studies

    Science.gov (United States)

    Banuppriya, Govindharasu; Sribalan, Rajendran; Padmini, Vediappen

    2018-03-01

    Curcumin-sulfonamide hybrids (4a-e) were synthesized and their in vitro antioxidant, anti-inflammatory and anticancer activities were studied. The synthesized compounds showed a very good potent activity towards antioxidant and anti-inflammatory studies rather than its parent as well as standard. These compounds have exhibited an excellent toxicity effect to the cancer cell lines such as A549 and AGS. The compounds 4a and 4c have showed good anticancer activity than curcumin. The molecular docking studies were also performed against various Epidermal Growth Factor Receptor (EGFR) enzymes. The DFT calculations were also done in order to support the docking results.

  15. Synthesis and Biological Evaluation of Sulfonamide 1,3-Thiazole Azo Dyes and Their Textile Printing Application

    OpenAIRE

    , K.A. Ahmed; , H.M. El-Hennawi; , H.A. Abdel-Aziz; , M.A. Elkashouti

    2016-01-01

    1,3-Thiazoles and sulphonamides have received considerable attention, because they are widely employed as promising chromophores as well as their biological activities as anti-microbial, antiviral, anti-tumor agents. The synthetic potency of sulfonamide hydrazonyl chlorides, were used as a key precursor in the synthesis of some new 1,3-thiazoles, in this study the synthesis of 4-[(2-amino-4-methylthiazol-5-yl)diazenyl]benzene sulfonamides were used as a synthone for the synthesis of 1,3-thiaz...

  16. Carbonic anhydrase inhibitors; phosphoryl-sulfonamides--a new class of high affinity inhibitors of isozymes I and II.

    Science.gov (United States)

    Fenesan, I; Popescu, R; Scozzafava, A; Crucin, V; Mateiciuc, E; Bauer, R; Ilies, M A; Supuran, C T

    2000-01-01

    A series of phosphorylated aromatic/heterocyclic sulfonamides with the general formula ArSO2NHPO3H2 have been prepared by condensing ArSO2NH2 with phosphorus pentachloride, followed by controlled hydrolysis in the presence of formic acid. The new derivatives generally act as stronger inhibitors of two carbonic anhydrase (CA) isozymes, CA I and CA II, as compared to the parent unsubstituted sulfonamides from which they were obtained. The inhibition mechanism by this new class of CA inhibitors, as well as structure activity correlations for the series of investigated derivatives, are also discussed.

  17. Synthesis and Antiviral Activity of 5‑(4‑Chlorophenyl-1,3,4-Thiadiazole Sulfonamides

    Directory of Open Access Journals (Sweden)

    Yuping Zhang

    2010-12-01

    Full Text Available Starting from 4-chlorobenzoic acid, 10 new 5-(4-chlorophenyl-N-substituted-N-1,3,4-thiadiazole-2-sulfonamide derivatives were synthesized in six-steps. Esterification of 4-chlorobenzoic acid with methanol and subsequent hydrazination, salt formation and cyclization afforded 5-(4-chlorophen-yl-1,3,4-thiadiazole-2-thiol (5. Conversion of this intermediate into sulfonyl chloride 6, followed by nucleophilic attack of the amines gave the title sulfonamides 7a-7j whose structures were confirmed by NMR, IR and elemental analysis. The bioassay tests showed that compounds 7b and 7i possessed certain anti-tobacco mosaic virus activity.

  18. Intermolecular Anti-Markovnikov Hydroamination of Unactivated Alkenes with Sulfonamides Enabled by Proton-Coupled Electron Transfer.

    Science.gov (United States)

    Zhu, Qilei; Graff, David E; Knowles, Robert R

    2018-01-17

    Here we report a catalytic method for the intermolecular anti-Markovnikov hydroamination of unactivated alkenes using primary and secondary sulfonamides. These reactions occur at room temperature under visible light irradiation and are jointly catalyzed by an iridium(III) photocatalyst, a dialkyl phosphate base, and a thiol hydrogen atom donor. Reaction outcomes are consistent with the intermediacy of an N-centered sulfonamidyl radical generated via proton-coupled electron transfer activation of the sulfonamide N-H bond. Studies outlining the synthetic scope (>60 examples) and mechanistic features of the reaction are presented.

  19. pKJ1, a naturally occurring conjugative plasmid coding for toluene degradation and resistance to streptomycin and sulfonamides

    Energy Technology Data Exchange (ETDEWEB)

    Yano, K.; Nishi, T.

    1980-08-01

    Pseudomonas sp. TA8 isolated by m-toluate enrichment from an aqueous sample metabolized toluene and m- and p-xylenes via the meta cleavage pathway, and manifested specific resistance to streptomycin and sulfonamides. A variety of experiments revealed that the pKJ1 plasmid of about 150 megadaltons carried by TA8 specified both the toluene and xylene degradative function (the Tol function) and streptomycin/sulfonamide resistance. The deletion of a segment of pKJ1 (about 22 megadaltons) resulted in the loss of the Tol function. pKJ1 was not assigned to Pseudomonas incompatibility group P-1, P-2, P-3, or P-9.

  20. Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum.

    Science.gov (United States)

    Oku, Naoya; Matsumoto, Miyako; Yonejima, Kohsuke; Tansei, Keijiroh; Igarashi, Yasuhiro

    2014-01-01

    Macroscopic gelatinous colonies of freshwater cyanobacterium Aphanothece sacrum, a luxury ingredient for Japanese cuisine, were found to contain a new oxylipin-derived macrolide, sacrolide A (1), as an antimicrobial component. The configuration of two chiral centers in 1 was determined by a combination of chiral anisotropy analysis and conformational analysis of different ring-opened derivatives. Compound 1 inhibited the growth of some species of Gram-positive bacteria, yeast Saccharomyces cerevisiae and fungus Penicillium chrysogenum, and was also cytotoxic to 3Y1 rat fibroblasts. Concern about potential food intoxication caused by accidental massive ingestion of A. sacrum was dispelled by the absence of 1 in commercial products. A manual procedure for degrading 1 in raw colonies was also developed, enabling a convenient on-site detoxification at restaurants or for personal consumption.

  1. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor.

    Science.gov (United States)

    Mirando, Adam C; Fang, Pengfei; Williams, Tamara F; Baldor, Linda C; Howe, Alan K; Ebert, Alicia M; Wilkinson, Barrie; Lounsbury, Karen M; Guo, Min; Francklyn, Christopher S

    2015-08-14

    Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans.

  2. Angioimmunoblastic T-cell lymphoma (AIL-TCL) following macrolide administration.

    Science.gov (United States)

    Sasaki, T Y; Sumida, K N

    2000-02-01

    Angioimmunoblastic Lymphadenopathy with Dysproteinemia (AILD) is a rare benign reactive process which often follows exposure to certain drugs such as penicillin. Treatment with corticosteroids usually reverses the process, however there have been reports of 18% of cases evolving into non-Hodgkins lymphoma. In our case report, we present a relatively healthy woman with history of various drug hypersensitivities who developed AILD and resultant lymphoma after treatment with azithromycin. A review of the literature has failed to find reports of AILD following macrolide exposure. Clonality, not present in other forms of hyperplasia, is present in AILD and immunosuppression may account for this difference. It is difficult to say whether the drugs are simply coincidently associated or actually cause, maintain, or exacerbate clonality in AILD and facilitate malignant transformation.

  3. Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

    Directory of Open Access Journals (Sweden)

    Naoya Oku

    2014-08-01

    Full Text Available Macroscopic gelatinous colonies of freshwater cyanobacterium Aphanothece sacrum, a luxury ingredient for Japanese cuisine, were found to contain a new oxylipin-derived macrolide, sacrolide A (1, as an antimicrobial component. The configuration of two chiral centers in 1 was determined by a combination of chiral anisotropy analysis and conformational analysis of different ring-opened derivatives. Compound 1 inhibited the growth of some species of Gram-positive bacteria, yeast Saccharomyces cerevisiae and fungus Penicillium chrysogenum, and was also cytotoxic to 3Y1 rat fibroblasts. Concern about potential food intoxication caused by accidental massive ingestion of A. sacrum was dispelled by the absence of 1 in commercial products. A manual procedure for degrading 1 in raw colonies was also developed, enabling a convenient on-site detoxification at restaurants or for personal consumption.

  4. The effect of milk on plasmatic and tissue levels of macrolides: in vivo study in rats

    Directory of Open Access Journals (Sweden)

    F. C. Groppo

    2009-01-01

    Full Text Available

    The ingestion of milk with drugs, particularly some antibiotics, is frequently recommended in order to decrease possible gastrointestinal discomfort. The objective of this study was to assess the interference of milk in the absorption and tissue levels of macrolide antibiotics (erythromycin, clarithromycin, roxithromycin and azithromycin. Forty female rats received surgicallyimplanted PVC sponges on their backs. One week later, granulomatous tissue was observed and the animals were divided into eight groups, which received erythromycin, clarithromycin, roxithromycin and azithromycin with and without milk. One hour after administration of antibiotic, the animals were sacrificed. The serum and tissue samples were submitted to microbiological assay with Micrococcus luteus ATCC 9341, in order to determine drug concentration. Milk did not cause any reduction in the serum and tissue levels of azithromycin and clarithromycin (p>0.05,t-test. However, ingestion of milk reduced by approximately 28.7% the roxithromycin (p<0.0001, t-test and by 34.1% the erythromycin (p<0.0001, t test serum concentrations. Similar effects were observed on tissue levels. Milk ingestion caused a reduction of approximately 20.8% in the roxithromycin (p<0.0001, t-test and 40% in the erythromycin (p<0.0001, t-test tissue levels. We concluded that erythromycin and roxithromycin should be not administered with milk. Keywords: Pharmacokinetics, macrolides, milk, serum concentration

  5. Antimicrobial activity of solithromycin against serotyped macrolide-resistant Streptococcus pneumoniae isolates collected from U.S. medical centers in 2012.

    Science.gov (United States)

    Farrell, D J; Mendes, R E; Jones, R N

    2015-04-01

    Solithromycin, a next-generation macrolide and novel fluoroketolide, was tested against a 2012 collection of serotyped U.S. macrolide-resistant Streptococcus pneumoniae isolates associated with community-acquired bacterial pneumonia (CABP). Against all 272 isolates, solithromycin demonstrated high potency (MIC50/90, 0.06/0.25 μg/ml), and it inhibited all strains at MICs of ≤0.5 μg/ml, including the two most prevalent macrolide-resistant serotypes (19A and 35B). These data support the continued clinical development of solithromycin for the treatment of multidrug-resistant CABP. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Antimicrobial Activity of Solithromycin against Serotyped Macrolide-Resistant Streptococcus pneumoniae Isolates Collected from U.S. Medical Centers in 2012

    OpenAIRE

    Farrell, D. J.; Mendes, R. E.; Jones, R. N.

    2015-01-01

    Solithromycin, a next-generation macrolide and novel fluoroketolide, was tested against a 2012 collection of serotyped U.S. macrolide-resistant Streptococcus pneumoniae isolates associated with community-acquired bacterial pneumonia (CABP). Against all 272 isolates, solithromycin demonstrated high potency (MIC50/90, 0.06/0.25 μg/ml), and it inhibited all strains at MICs of ≤0.5 μg/ml, including the two most prevalent macrolide-resistant serotypes (19A and 35B). These data support the continue...

  7. Photolytic degradation of sulfamethoxazole and trimethoprim using UV-A, UV-C and vacuum-UV (VUV).

    Science.gov (United States)

    Kim, Hyun Young; Kim, Tae-Hun; Yu, Seungho

    2015-01-01

    The photolytic degradation of the non-degradable pharmaceuticals sulfamethoxazole (SMX) and trimethoprim (TMP) in an aqueous solution was investigated using three kinds of low-pressure mercury lamp UV-A (352 nm), UV-C (254 nm), and vacuum-UV (VUV, 185 nm and 254 nm). The degradation rates were highly dependent on the target compounds as well as the UV sources. No degradation of the target compounds was observed using UV-A treatment, because there was no overlap between the UV-A emission spectrum and absorption spectrum of the target compounds. On the other hand, UVC and VUV revealed higher reactivity. The results also indicated that SMX had a greater potential to react photochemically than TMP. Among the UV sources, VUV was the most effective process for the degradation of target compounds. Furthermore, the addition of oxidants such as hydrogen peroxide (H2O2) and sodium persulfate (Na2S2O8) to the reaction system improved the overall degradation rate significantly.The experimental results for the VUV-irradiated samples with the addition of methanol as a hydroxyl radical scavenger revealed that hydroxyl radicals contribute significantly to the elimination of the target compound. Overall, the degradation rate of the target compounds was in the order: VUV = UV-C > UV-A for sulfamethoxazole and VUV/H2O2 > VUV/ Na2S2O8 > VUV >UV-C >UV-A for trimethoprim.

  8. Impacts of solids retention time on trace organic compound attenuation and bacterial resistance to trimethoprim and sulfamethoxazole.

    Science.gov (United States)

    Neyestani, Majid; Dickenson, Eric; McLain, Jean; Robleto, Eduardo; Rock, Channah; Gerrity, Daniel

    2017-09-01

    Bacteria can grow in the presence of trimethoprim and sulfamethoxazole by expressing antibiotic resistance genes or by acquiring thymine or thymidine from environmental reservoirs to facilitate DNA synthesis. The purpose of this study was to evaluate whether activated sludge serves as a reservoir for thymine or thymidine, potentially impacting the quantification of antibiotic resistant bacteria. This study also assessed the impacts of varying solids retention time (SRT) on trimethoprim and sulfamethoxazole removal during wastewater treatment and single and multi-drug resistance. When assayed in the presence of the antibiotics at standard clinical concentrations, up to 40% increases in the relative prevalence of resistant bacteria were observed with (1) samples manually augmented with reagent-grade thymidine, (2) samples manually augmented with sonicated biomass (i.e., cell lysate), (3) samples manually augmented with activated sludge filtrate, and (4) activated sludge samples collected from reactors with longer SRTs. These observations suggest that longer SRTs may select for antibiotic resistant bacteria and/or result in false positives for antibiotic resistance due to higher concentrations of free thymine, thymidine, or other extracellular constituents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial

    Directory of Open Access Journals (Sweden)

    Uberos J

    2012-05-01

    Full Text Available Jose Uberos,1 Mercedes Nogueras-Ocana,2 Verónica Fernandez-Puentes,1 Rocio Rodriguez-Belmonte,1 Eduardo Narbona-López,1 Antonio Molina-Carballo,1 Antonio Munoz-Hoyos11Paediatric Clinical Management Unit, San Cecilio University Clinical Hospital, Avda de Madrid s/n, Granada, Spain; 2Paediatric Urology, San Cecilio University Clinical Hospital, Avda de Madrid s/n, Granada, SpainObjectives: The present study forms part of the ISRCTN16968287 clinical assay. The objective of this study was to determine the effectiveness of cranberry syrup in the prophylaxis of recurrent urinary tract infection (UTI.Design: Phase III randomized clinical trial.Setting: The study was conducted at the San Cecilio Clinical Hospital (Granada, Spain.Participants: A total of 192 patients were recruited. The subjects were aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI (more than two episodes of infection in the last 6 months, associated or otherwise with vesicoureteral reflux of any degree, or renal pelvic dilatation associated with UTI. Criteria for exclusion from recruitment to the study included the co-existence of UTI with other infectious diseases or with metabolic diseases, chronic renal insufficiency, and the presence of allergy or intolerance to any of the components of cranberry syrup or trimethoprim.Primary outcome measures: The primary objective was to determine the risk of UTI associated with each intervention.Results: Of the 198 patients initially eligible, 192 were finally included in the study to receive either cranberry syrup or trimethoprim. UTI was observed in 47 patients, 17 of whom were males and 30 females. We recruited 95 patients diagnosed with recurrent UTI on entry; during follow-up, 26 patients had a UTI (27.4%, 95% CI: 18.4%–36.3%. Six patients (6.3% were male and 20 (21.1% were female. Eighteen patients (18.9% of the total, 95% CI: 11%–26.3% receiving trimethoprim had a UTI and eight patients (8

  10. Impact of manure-related DOM on sulfonamide transport in arable soils

    Science.gov (United States)

    Zhou, Dan; Thiele-Bruhn, Sören; Arenz-Leufen, Martina Gesine; Jacques, Diederik; Lichtner, Peter; Engelhardt, Irina

    2016-09-01

    Field application of livestock manure introduces colloids and veterinary antibiotics, e.g. sulfonamides (SAs), into farmland. The presence of manure colloids may potentially intensify the SAs-pollution to soils and groundwater by colloid-facilitated transport. Transport of three SAs, sulfadiazine (SDZ), sulfamethoxypyridazine (SMPD), and sulfamoxole (SMOX), was investigated in saturated soil columns with and without manure colloids from sows and farrows, weaners, and fattening pigs. Experimental results showed that colloid-facilitated transport of SMOX was significant in the presence of manure colloids from fattening pigs with low C/N ratio, high SUVA280 nm and protein C, while manure colloids from sows and farrows and weaners had little effect on SMOX transport. In contrast, only retardation was observed for SDZ and SMPD when manure colloids were present. Breakthrough curves (BTCs) of colloids and SAs were replicated well by a newly developed numerical model that considers colloid-filtration theory, competitive kinetic sorption, and co-transport processes. Model results demonstrate that mobile colloids act as carriers for SMOX, while immobile colloids block SMOX from sorbing onto the soil. The low affinity of SMOX to sorb on immobile colloids prevents aggregation and also promotes SMOX's colloid-facilitated transport. Conversely, the high affinity of SDZ and SMPD to sorb on all types of immobile colloids retarded their transport. Thus, manure properties play a fundamental role in increasing the leaching risk of hydrophobic sulfonamides.

  11. Rapid startup of thermophilic anaerobic digester to remove tetracycline and sulfonamides resistance genes from sewage sludge.

    Science.gov (United States)

    Xu, Rui; Yang, Zhao-Hui; Wang, Qing-Peng; Bai, Yang; Liu, Jian-Bo; Zheng, Yue; Zhang, Yan-Ru; Xiong, Wei-Ping; Ahmad, Kito; Fan, Chang-Zheng

    2018-01-15

    Spread of antibiotic resistance genes (ARGs) originating from sewage sludge is highlighted as an eminent health threat. This study established a thermophilic anaerobic digester using one-step startup strategy to quickly remove tetracycline and sulfonamides resistance genes from sewage sludge. At least 20days were saved in the startup period from mesophilic to thermophilic condition. Based on the results of 16S rDNA amplicons sequencing and predicted metagenomic method, the successful startup largely relied on the fast colonization of core thermophilic microbial population (e.g. Firmicutes, Proteobacteria, Actinobacteria). Microbial metabolic gene pathways for substrate degradation and methane production was also increased by one-step mode. In addition, real-time quantitative PCR approach revealed that most targeted tetracycline and sulfonamides resistance genes ARGs (sulI, tetA, tetO, tetX) were substantially removed during thermophilic digestion (removal efficiency>80%). Network analysis showed that the elimination of ARGs was attributed to the decline of their horizontal (intI1 item) and vertical (potential hosts) transfer-related elements under high-temperature. This research demonstrated that rapid startup thermophilic anaerobic digestion of wastewater solids would be a suitable technology for reducing quantities of various ARGs. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Purification and characterization of carbonic anhydrase from sheep kidney and effects of sulfonamides on enzyme activity.

    Science.gov (United States)

    Demirdağ, Ramazan; Çomaklı, Veysel; Şentürk, Murat; Ekinci, Deniz; İrfan Küfrevioğlu, Ö; Supuran, Claudiu T

    2013-03-15

    Carbonic anhydrase (CA, EC: 4.2.1.1) was purified from sheep kidney by affinity chromatography on a Sepharose 4B-tyrosine-sulfanilamide column. By means of two consecutive procedures, the enzyme (sCA) was purified 227.61-fold with a yield of 60.75%, and a specific activity of 838.89U/mg proteins. The optimum temperature, ionic strength and pH were determined to be 35°C, 20mM and 8.5, respectively. The molecular weight determined by SDS-PAGE was found to be 29kDa. The kinetic parameters, KM and Vmax values were determined for the 4-nitrophenyl acetate (p-NpA) hydrolysis reaction. Some sulfonamides were tested as inhibitors against the purified CAs enzyme. The Ki constants for benzenesulfonamide (1), sulfanilamide (2), mafenide (3), 4-(2-aminoethyl) benzenesulfonamide (4), 4-methyl-benzenesulfonamide (5), 2-bromo-benzenesulfonamide (6), naphthalene-2-sulfonamide (7), 4-amino-6-chlorobenzene-1,3-disulfonamide (8) and saccharin (9) were in the range 1.348-69.31μM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Integrated disposable electrochemical immunosensors for the simultaneous determination of sulfonamide and tetracycline antibiotics residues in milk.

    Science.gov (United States)

    Conzuelo, Felipe; Campuzano, Susana; Gamella, María; Pinacho, Daniel G; Reviejo, A Julio; Marco, M Pilar; Pingarrón, José M

    2013-12-15

    The design, preparation and analytical performance of a novel integrated amperometric immunosensor based on the immobilization of selective capture antibodies on the surface of Protein G-modified screen-printed dual carbon electrodes (SPdCEs) for the multiplexed determination of sulfonamide and tetracycline antibiotics residues in milk is reported in this work. Protein G was covalently immobilized onto a 4-aminobenzoic acid (4-ABA) film grafted on the disposable electrode, and a direct competitive immunoassay using horseradish peroxidase (HRP)-labeled tracers was performed. The amperometric responses measured at -0.2 V vs. the silver pseudo-reference electrode of the SPdCE upon the addition of H2O2 in the presence of hydroquinone (HQ) as mediator were used to monitor the extent of the immunoreactions. The developed methodology showed very low limits of detection (in the low ppb level) for sulfonamide and tetracycline antibiotics tested in untreated milk samples, and a good selectivity against other antibiotic residues frequently detected in milk and dairy products. The usefulness of the dual immunosensor was demonstrated by analyzing spiked milk samples as well as a reference milk containing a certified oxytetracycline (OTC) content. Good recoveries were attained in an analysis time of 30 min. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Study of the Chemical Space of Selected Bacteriostatic Sulfonamides from an Information Theory Point of View.

    Science.gov (United States)

    López-Rosa, Sheila; Molina-Espíritu, Moyocoyani; Esquivel, Rodolfo O; Soriano-Correa, Catalina; Dehesa, Jésus S

    2016-12-05

    The relative structural location of a selected group of 27 sulfonamide-like molecules in a chemical space defined by three information theory quantities (Shannon entropy, Fisher information, and disequilibrium) is discussed. This group is composed of 15 active bacteriostatic molecules, 11 theoretically designed ones, and para-aminobenzoic acid. This endeavor allows molecules that share common chemical properties through the molecular backbone, but with significant differences in the identity of the chemical substituents, which might result in bacteriostatic activity, to be structurally classified and characterized. This is performed by quantifying the structural changes on the electron density distribution due to different functional groups and number of electrons. The macroscopic molecular features are described by means of the entropy-like notions of spatial electronic delocalization, order, and uniformity. Hence, an information theory three-dimensional space (IT-3D) emerges that allows molecules with common properties to be gathered. This space witnesses the biological activity of the sulfonamides. Some structural aspects and information theory properties can be associated, as a result of the IT-3D chemical space, with the bacteriostatic activity of these molecules. Most interesting is that the active bacteriostatic molecules are more similar to para-aminobenzoic acid than to the theoretically designed analogues. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1receptor ligand antagonists.

    Science.gov (United States)

    Murineddu, Gabriele; Deligia, Francesco; Ragusa, Giulio; García-Toscano, Laura; Gómez-Cañas, María; Asproni, Battistina; Satta, Valentina; Cichero, Elena; Pazos, Ruth; Fossa, Paola; Loriga, Giovanni; Fernández-Ruiz, Javier; Pinna, Gerard A

    2018-01-01

    A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB 1 and CB 2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB 1 receptors (K i values of 44.6 nM for CB 1 receptors and >40 μM for CB 2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB 1 receptors with K i values of 75.5 and 73.2 nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB 1 receptor in the [ 35 S]-GTPγS binding assays, and none showed adequate predictive blood-brain barrier permeation, exhibiting low estimated LD 50 . However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB 1 receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Removal of tetracyclines, sulfonamides, and quinolones by industrial-scale composting and anaerobic digestion processes.

    Science.gov (United States)

    Liu, Hang; Pu, Chengjun; Yu, Xiaolu; Sun, Ying; Chen, Junhao

    2018-02-15

    This study evaluated and compared the removal of antibiotics by industrial-scale composting and anaerobic digestion at different seasons. Twenty compounds belonged to three classes of widely used veterinary antibiotics (i.e., tetracyclines, sulfonamides, and quinolones) were investigated. Results show that of the three groups of antibiotics, tetracyclines were dominant in swine feces and poorly removed by anaerobic digestion with significant accumulation in biosolids, particularly in winter. Compared to that in winter, a much more effective removal (> 97%) by anaerobic digestion was observed for sulfonamides in summer. By contrast, quinolones were the least abundant antibiotics in swine feces and exhibited a higher removal by anaerobic digestion in winter than in summer. The overall removal of antibiotics by aerobic composting could be more than 90% in either winter or summer. Nevertheless, compost products from livestock farms in Beijing contained much higher antibiotics than commercial organic fertilizers. Thus, industrial composting standards should be strictly applied to livestock farms to further remove antibiotics and produce high quality organic fertilizer.

  17. Graphene-functionalized melamine sponges for microextraction of sulfonamides from food and environmental samples.

    Science.gov (United States)

    Chatzimitakos, Theodoros; Samanidou, Victoria; Stalikas, Constantine D

    2017-11-03

    The study describes the functionalization of melamine sponges with graphene and its use as an adsorbent for the microextraction of sulfonamides from food and environmental samples. The graphene-functionalized melamine sponge (GMeS) was prepared by an easy, one-step procedure, which complies with the principles of green chemistry and is proved advantageous over previously described methods. The applicability of the GMeS in extraction procedures was studied and an analytical method for the determination of sulfonamides in milk, eggs and lake water was developed and validated according to SANCO/12571/2013 guideline. The developed method was highly accurate and reproducible, while the limits of quantification were found to be relatively low (0.31-0.91μgkg -1 , 0.96-1.32μgkg -1 and 0.10-0.29μgL -1 in the case of milk, eggs and lake water respectively). Furthermore, matrix effects were absent in all cases, since the microextraction procedure serves also as a clean-up step. The low cost of synthesis, the environmentally friendly conditions, the efficiency and high extraction recoveries are some additional advantages of the proposed procedure. To the best of our knowledge, this is the first time that a GMeS is prepared in a straightforward way and used for analytical purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Competitive sorption affinity of sulfonamides and chloramphenicol antibiotics toward functionalized biochar for water and wastewater treatment.

    Science.gov (United States)

    Ahmed, Mohammad Boshir; Zhou, John L; Ngo, Huu Hao; Guo, Wenshan; Johir, Md Abu Hasan; Belhaj, Dalel

    2017-08-01

    Competitive sorption of sulfamethazine (SMT), sulfamethoxazole (SMX), sulfathiazole (STZ) and chloramphenicol (CP) toward functionalized biochar (fBC) was highly pH dependent with maximum sorption at pH ∼4.0-4.25. Equilibrium data were well represented by the Langmuir and Freundlich models in the order STZ>SMX>CP>SMT. Kinetics data were slightly better fitted by the pseudo second-order model than pseudo first-order and intra-particle-diffusion models. Maximum sorptive interactions occurred at pH 4.0-4.25 through H-bonds formations for neutral sulfonamides species and through negative charge assisted H-bond (CAHB) formation for CP, in addition to π-π electron-donor-acceptor (EDA) interactions. EDA was the main mechanism for the sorption of positive sulfonamides species and CP at pH7.0 was regulated by H-bond formation and proton exchange with water by forming CAHB, respectively. The results suggested fBC to be highly efficient in removing antibiotics mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Impact of manure-related DOM on sulfonamide transport in arable soils.

    Science.gov (United States)

    Zhou, Dan; Thiele-Bruhn, Sören; Arenz-Leufen, Martina Gesine; Jacques, Diederik; Lichtner, Peter; Engelhardt, Irina

    2016-09-01

    Field application of livestock manure introduces colloids and veterinary antibiotics, e.g. sulfonamides (SAs), into farmland. The presence of manure colloids may potentially intensify the SAs-pollution to soils and groundwater by colloid-facilitated transport. Transport of three SAs, sulfadiazine (SDZ), sulfamethoxypyridazine (SMPD), and sulfamoxole (SMOX), was investigated in saturated soil columns with and without manure colloids from sows and farrows, weaners, and fattening pigs. Experimental results showed that colloid-facilitated transport of SMOX was significant in the presence of manure colloids from fattening pigs with low C/N ratio, high SUVA280nm and protein C, while manure colloids from sows and farrows and weaners had little effect on SMOX transport. In contrast, only retardation was observed for SDZ and SMPD when manure colloids were present. Breakthrough curves (BTCs) of colloids and SAs were replicated well by a newly developed numerical model that considers colloid-filtration theory, competitive kinetic sorption, and co-transport processes. Model results demonstrate that mobile colloids act as carriers for SMOX, while immobile colloids block SMOX from sorbing onto the soil. The low affinity of SMOX to sorb on immobile colloids prevents aggregation and also promotes SMOX's colloid-facilitated transport. Conversely, the high affinity of SDZ and SMPD to sorb on all types of immobile colloids retarded their transport. Thus, manure properties play a fundamental role in increasing the leaching risk of hydrophobic sulfonamides. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Spectroscopic characterization, antimicrobial activity, DFT computation and docking studies of sulfonamide Schiff bases

    Science.gov (United States)

    Mondal, Sudipa; Mandal, Santi M.; Mondal, Tapan Kumar; Sinha, Chittaranjan

    2017-01-01

    Schiff bases synthesised from the condensation of 2-(hydroxy)naphthaldehyde and sulfonamides (sufathiazole (STZ), sulfapyridine (SPY), sulfadiazine (SDZ), sulfamerazine (SMZ) and sulfaguanidine (SGN)) are characterized by different spectroscopic data (FTIR, UV-Vis, Mass, NMR) and two of them, (E)-4-(((2-hydroxynaphthalen-1-yl)methylene)amino)-N-(thiazol-2-yl)benzenesulfonamide (1a) and (E)-N-(diaminomethylene)-4-(((2-hydroxynaphthalen-1-yl)methylene)amino)benzenesulfonamide (1e) have been confirmed by single crystal X-ray structure determination. Antimicrobial activities of the Schiff bases have been evaluated against certified and resistant Gram positive (Staphylococcus aureus, Enterococcus facelis) and Gram negative (Streptococcus pyogenes, Salmonella typhi, Shigella dysenteriae, Shigella flexneri, Klebsiella pneumonia) pathogens. Performance of Schiff base against the resistant pathogens are better than standard stain and MIC data lie 32-128 μg/ml while parent sulfonamides are effectively inactive (MIC >512 μg/ml). The DFT optimized structures of the Schiff bases have been used to accomplish molecular docking studies with DHPS (dihydropteroate synthase) protein structure (downloaded from Protein Data Bank) to establish the most preferred mode of interaction. ADMET filtration, Cytotoxicity (MTT assay) and haemolysis assay have been examined for evaluation of druglike character.

  1. Thermodynamic aspects of solubility, solvation and partitioning processes of some sulfonamides

    Energy Technology Data Exchange (ETDEWEB)

    Perlovich, German L., E-mail: glp@isc-ras.r [Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka (Russian Federation); Institute of Solution Chemistry, Russian Academy of Sciences, 153045 Ivanovo (Russian Federation); Ryzhakov, Alex M. [Institute of Solution Chemistry, Russian Academy of Sciences, 153045 Ivanovo (Russian Federation); Strakhova, Nadezda N.; Kazachenko, Vladimir P. [Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka (Russian Federation); Schaper, Klaus-Juergen [Research Center Borstel, Leibniz Center for Medicine and Biosciences, D-23845 Borstel (Germany); Raevsky, Oleg A. [Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka (Russian Federation)

    2011-05-15

    Research highlights: {yields} The thermodynamic aspects of sublimation processes of some sulfonamides were studied by investigating the temperature dependence of vapor pressure using the transpiration method. {yields} Solubility processes of the compounds in water, phosphate buffer with pH 7.4 and n-octanol were investigated and corresponding thermodynamic functions were calculated as well. {yields} Thermodynamic characteristics of the sulfonamides solvation were evaluated. - Abstract: The thermodynamic aspects of sublimation processes of three sulfonamides with the general structures C{sub 6}H{sub 5}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-NO{sub 2}) and 4-NH{sub 2}-C{sub 6}H{sub 4}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-NO{sub 2}; 4-CN) were studied by investigating the temperature dependence of vapor pressure using the transpiration method. These data together with those obtained earlier for C{sub 6}H{sub 5}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-Cl) and 4-NH{sub 2}-C{sub 6}H{sub 4}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-Cl; 4-OMe; 4-C{sub 2}H{sub 5}) were analyzed and compared. A correlation was derived between sublimation Gibbs free energies and the sum of H-bond acceptor factors of the molecules. Solubility processes of the compounds in water, phosphate buffer with pH 7.4 and n-octanol (as phases modeling various drug delivery pathways) were investigated and corresponding thermodynamic functions were calculated as well. Thermodynamic characteristics of the sulfonamides solvation were evaluated. Also in this case a correlation between solubility/solvation Gibbs free energy values and the sum of H-bond acceptor factors was observed. For the sulfonamides with various substituents at para-position the processes of transfer from one solvent (water or buffer) to n-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight

  2. Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV-infected women in Kenya.

    Science.gov (United States)

    Green, Michael; Otieno, Kephas; Katana, Abraham; Slutsker, Laurence; Kariuki, Simon; Ouma, Peter; González, Raquel; Menendez, Clara; ter Kuile, Feiko; Desai, Meghna

    2016-01-05

    Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed. A double-blinded, placebo-controlled study was conducted with 124 HIV-infected, pregnant women on a standard regimen of sulfamethoxazole/trimethoprim prophylaxis. Seventy-two subjects received three doses of mefloquine (15 mg/kg) at monthly intervals. Dried blood spots were collected from both placebo and mefloquine arms four to 672 h post-administration and on day 7 following a second monthly dose of mefloquine. A novel high-performance liquid chromatographic method was developed to simultaneously measure mefloquine, sulfamethoxazole and trimethoprim from each blood spot. Non-compartmental methods using a naïve-pooled data approach were used to determine mefloquine pharmacokinetic parameters. Sulfamethoxazole/trimethoprim prophylaxis did not noticeably influence mefloquine pharmacokinetics relative to reported values. The mefloquine half-life, observed clearance (CL/f), and area-under-the-curve (AUC0→∞) were 12.0 days, 0.035 l/h/kg and 431 µg-h/ml, respectively. Although trimethoprim steady-state levels were not significantly different between arms, sulfamethoxazole levels showed a significant 53% decrease after mefloquine administration relative to the placebo group and returning to pre-dose levels at 28 days. Although a transient decrease in sulfamethoxazole levels was observed, there was no change in hospital admissions due to secondary bacterial infections, implying that mefloquine may have provided antimicrobial protection.

  3. Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.

    Science.gov (United States)

    von Dach, E; Morel, C M; Murthy, A; Pagani, L; Macedo-Vinas, M; Olearo, F; Harbarth, S

    2017-09-01

    Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides

    Science.gov (United States)

    Dunetz, Joshua R.; Danheiser, Rick L.

    2010-01-01

    A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amides with KHMDS followed by reaction with CuI and an alkynyl bromide. PMID:14535766

  5. Chemical Genetic Screening Identifies Sulfonamides That Raise Organellar pH and Interfere with Endocytic and Exocytic Membrane Traffic

    Science.gov (United States)

    Nieland, Thomas J. F.; Feng, Yan; Brown, Jing Xu; Chuang, Tuan Daniel; Buckett, Peter D.; Wang, Jin; Xie, Xiao-Song; McGraw, Timothy E.; Kirchhausen, Tomas; Wessling-Resnick, Marianne

    2008-01-01

    Chemical genetics seeks to identify small molecules that afford functional dissection of cell biological pathways. Previous screens for small molecule inhibitors of exocytic membrane traffic yielded the identification and characterization of several compounds that block traffic from the Golgi to the cell surface as well as transport from the endoplasmic reticulum to the Golgi network. Here, we screened these inhibitors for potential effects on endocytic membrane traffic. Two structurally related sulfonamides were found to be potent and reversible inhibitors of transferrin-mediated iron uptake. These inhibitors do not block endoplasmic reticulum-to-Golgi transport, but do disrupt Golgi-to-cell surface traffic. The compounds are members of a novel class of sulfonamides that elevate endosomal and lysosomal pH, down-regulate cell surface receptors, and impair recycling of internalized transferrin receptors to the plasma membrane. In vitro experiments revealed that the sulfonamides directly inhibit adenosine triphosphate (ATP) hydrolysis by the V-ATPase and that they also possess a potent proton ionophore activity. While maintenance of organellar pH is known to be a critical factor in both endocytosis and exocytosis, the precise role of acidification, beyond the uncoupling of ligands from their receptors, remains largely unknown. Identification of this novel class of sulfonamide inhibitors provides new chemical tools to better understand the function of organelle pH in membrane traffic and the activity of V-ATPases in particular. PMID:15180825

  6. N-Arylation of amines, amides, imides and sulfonamides with arylboroxines catalyzed by simple copper salt/EtOH system

    Directory of Open Access Journals (Sweden)

    2008-11-01

    Full Text Available The coupling of arylboroxines with a variety of amines, amides, imides and sulfonamides catalyzed by a copper salt/EtOH system has been developed. In the absence of a base or additive the corresponding N-arylation products were obtained in moderate to excellent yields.

  7. Multifunctional monomers based on vinyl sulfonates and vinyl sulfonamides for crosslinking thiol-Michael polymerizations: monomer reactivity and mechanical behavior.

    Science.gov (United States)

    Sinha, Jasmine; Podgórski, Maciej; Huang, Sijia; Bowman, Christopher N

    2018-03-25

    Multifunctional vinyl sulfonates and vinyl sulfonamides were conveniently synthesized and assessed in thiol-Michael crosslinking polymerizations. The monomer reactivities, mechanical behavior and hydrolytic properties were analyzed and compared with those of analogous thiol-acrylate polymerizations. Materials with a broad range of mechanical properties and diverse hydrolytic stabilities were obtained.

  8. C5-Regioselective C-H fluorination of 8-aminoquinoline amides and sulfonamides with Selectfluor under metal-free conditions.

    Science.gov (United States)

    Zhang, Yingchao; Wen, Chunxia; Li, Jizhen

    2018-03-14

    A novel and efficient regioselective C-H fluorination of 8-aminoquinoline amides and sulfonamides at the C5 position was achieved. Using Selectfluor as a "F" reagent and HOAc as an additive, the reaction proceeds smoothly via a radical pathway. This method features metal-free conditions, a broad substrate scope and operational simplicity.

  9. Synthesis of chromone, quinolone, and benzoxazinone sulfonamide nucleosides as conformationally constrained inhibitors of adenylating enzymes required for siderophore biosynthesis.

    Science.gov (United States)

    Engelhart, Curtis A; Aldrich, Courtney C

    2013-08-02

    MbtA catalyzes the first committed step of mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) and is responsible for the incorporation of salicylic acid into the mycobactin siderophores. 5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS) is an extremely potent nucleoside inhibitor of MbtA that possesses excellent activity against whole-cell Mtb but suffers from poor bioavailability. In an effort to improve the bioavailability, we have designed four conformationally constrained analogues of Sal-AMS that remove two rotatable bonds and the ionized sulfamate group on the basis of computational and structural studies. Herein we describe the synthesis, biochemical, and microbiological evaluation of chromone-, quinolone-, and benzoxazinone-3-sulfonamide derivatives of Sal-AMS. We developed new chemistry to assemble these three heterocycles from common β-ketosulfonamide intermediates. The synthesis of the chromone- and quinolone-3-sulfonamide intermediates features formylation of a β-ketosulfonamide employing dimethylformamide dimethyl acetal to afford an enaminone that can react intramolecularly with a phenol or intermolecularly with a primary amine via addition-elimination reaction(s). The benzoxazinone-3-sulfonamide was prepared by nitrosation of a β-ketosulfonamide followed by intramolecular nucleophilic aromatic substitution. Mitsunobu coupling of these bicyclic sulfonamides with a protected adenosine derivative followed by global deprotection provides a concise synthesis of the respective inhibitors.

  10. Independent lesions of fixed drug eruption caused by trimethoprim-sulfamethoxazole and tenoxicam in the same patient: a rare case of polysensitivity.

    Science.gov (United States)

    Ozkaya-Bayazit, Esen

    2004-08-01

    Polysensitivity in fixed drug eruption is a rare finding that occurs because of chemically unrelated drugs. In cases of polysensitivity, the lesions may occur on identical or separate sites, the latter indicating the role of antigen-specific mechanisms in the site-specificity of fixed drug eruption. I herein report a patient with separate site involvement induced by trimethoprim-sulfamethoxazole and tenoxicam, a drug combination that has not been reported before. Reactivation of old trimethoprim-sulfamethoxazole-specific lesions after a long resting period was another striking feature.

  11. Synthesis of gamma,delta-unsaturated-beta-keto lactones via sequential cross metathesis-lactonization: a facile entry to macrolide antibiotic (-)-A26771B.

    Science.gov (United States)

    Gebauer, Julian; Blechert, Siegfried

    2006-03-03

    A simple access to gamma,delta-unsaturated-beta-keto lactones is presented, allowing a rapid total synthesis of the naturally occurring 16-membered macrolide antibiotic (-)-A26771B via cross metathesis, asymmetric dihydroxylation, and lactonization as the key steps.

  12. Real-life treatment of acute exacerbations of chronic bronchitis with moxifloxacin or macrolides: a comparative post-marketing surveillance study in general practice.

    Science.gov (United States)

    Schaberg, T; Möller, M; File, T; Stauch, K; Landen, H

    2006-01-01

    To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability. This prospective, non-interventional, multicentre study included out-patients with AECB whose last exacerbation was treated with a macrolide. The current AECB was treated either with moxifloxacin or with one of the macrolides azithromycin, clarithromycin or roxithromycin. Data were obtained on the patient's characteristics, disease and treatment history, the course of the current AECB including time to improvement and cure, and the final assessments of efficacy and tolerability. All adverse events were recorded in patients treated with moxifloxacin; for patients receiving macrolides, only drug-related adverse events were reported. 464 physicians treated 904 patients with moxifloxacin and 846 patients with one of the macrolides. Age, sex and body mass index were well matched between the two treatment groups. However, more moxifloxacin than macrolide patients presented with a generally bad condition (62.8% vs 48.6%). About 42% of patients in both groups had had chronic bronchitis for 1-5 years, and about 27% for 5-10 years. The mean number of AECBs in the previous 12 months was 2.7 and 2.6, respectively. Moxifloxacin was administered to most patients for 5 (43.8%) or 7 days (42.4%). Patients in the macrolide group were treated in most cases with clarithromycin 500 mg for 4-7 days, roxithromycin 300 mg for 6-7 days or azithromycin 500 mg for 3 days. Physicians assessed overall efficacy and tolerability as 'very good' or 'good' in 96.1% and 98.1%, respectively, of moxifloxacin-treated patients and in 67.5% and 91.7%, respectively, of macrolide-treated patients. The mean duration until improvement and cure of AECB was 3.2 days (+/- SD 1.5) and 6.2 days (+/- 2.6) in moxifloxacin

  13. Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3- and 4-(hetero)arylisoxazol-5-amine scaffolds.

    Science.gov (United States)

    Krasavin, Mikhail; Korsakov, Mikhail; Zvonaryova, Zhanna; Semyonychev, Evgenii; Tuccinardi, Tiziano; Kalinin, Stanislav; Tanç, Muhammet; Supuran, Claudiu T

    2017-03-15

    Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established and rationalized by in silico docking. These findings expand the structure-activity knowledge base for heterocycle-containing sulfonamide carbonic anhydrase inhibitors and further validate the power of direct electrophilic sulfochlorination as a means of introducing the pharmacophoric primary sulfonamide group into structurally diverse aromatic precursors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field

    Energy Technology Data Exchange (ETDEWEB)

    Topp, Edward, E-mail: ed.topp@agr.gc.ca; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

    2016-08-15

    The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1 mg kg{sup −1} soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10 mg kg{sup −1} macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1 mg kg{sup −1} macrolides. Rapid mineralization of {sup 14}C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. - Highlights: • The impact of field exposure on persistence of macrolide antibiotics was evaluated. • Soil samples were incubated in the laboratory with macrolides. • Field exposure resulted in more rapid dissipation of all macrolides. • Radiolabelled erythromycin and clarithromycin were rapidly mineralized

  15. A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

    Directory of Open Access Journals (Sweden)

    Straatmann Andrea

    2002-01-01

    Full Text Available Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective; alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women, with ages ranging from 30 to 57 years (mean 39.9. The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40% in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with

  16. A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

    Directory of Open Access Journals (Sweden)

    Andrea Straatmann

    Full Text Available Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective; alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women, with ages ranging from 30 to 57 years (mean 39.9. The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40% in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with

  17. Effects of a macrolide antibiotic on enamel formation in rat incisors--primary lesion of ameloblast at the transition stage.

    Science.gov (United States)

    Abe, Toshio; Miyajima, Hiroaki; Okada, Kosuke

    2003-09-01

    A novel macrolide antibiotic was administered orally to 5-week-old Jcl:Wistar rats at a dose of 5,000 mg/kg/day for 5 weeks, and then a half of animals were maintained without any treatment for 10 weeks. A white discolored lesion with horizontal stripes developed on the surface of the upper and lower incisors after dosing for 4 weeks, and these macroscopical incisal lesions disappeared with the eruption in 4 weeks after stop of administration. Histopathologically, increase in number of karyopycnosis of ameloblast at the transitional stage, vacuolar degeneration of ameloblast and cystic change in the maturation stage, and impaired iron pigment secretion at the pigmentation stage were observed. Microradiography, calcio-traumatic zones, which means hypocalcification, were observed on the superficial layer of enamel. These results suggest that the primary lesion induced by a novel macrolide antibiotic is the increased karyopycnosis of ameloblast at the transitional stage, and followed by later stage.

  18. [Amino acid and peptide derivatives of the tylosin family of macrolide antibiotics modified at the aldehyde group].

    Science.gov (United States)

    Sumbatian, N V; Kuznetsova, I V; Karpenko, V V; Fedorova, N V; Chertkov, V A; Korshunova, G A; Bogdanov, A A

    2010-01-01

    Fourteen new functionally active amino acid and peptide derivatives of the antibiotics tylosin, desmycosin, and 5-O-mycaminosyltylonolide were synthesized in order to study the interaction of the growing polypeptide chain with the ribosomal tunnel. The conjugation of various amino acids and peptides with a macrolide aldehyde group was carried out by two methods: direct reductive amination with the isolation of the intermediate Schiff bases or through binding via oxime using the preliminarily obtained derivatives of 2-aminooxyacetic acid.

  19. Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington.

    Science.gov (United States)

    Grimes, Matthew; Sahi, Sharon K; Godornes, B Charmie; Tantalo, Lauren C; Roberts, Neal; Bostick, David; Marra, Christina M; Lukehart, Sheila A

    2012-12-01

    Although azithromycin promised to be a safe and effective single-dose oral treatment of early syphilis, azithromycin treatment failure has been documented and is associated with mutations in the 23S rDNA of corresponding Treponema pallidum strains. The prevalence of strains harboring these mutations varies throughout the United States and the world. We examined T. pallidum strains circulating in Seattle, Washington, from 2001 to 2010 to determine the prevalence of 2 mutations associated with macrolide resistance and to determine whether these mutations were associated with certain T. pallidum strain types. Subjects were enrolled in a separate ongoing study of cerebrospinal fluid abnormalities in patients with syphilis. T. pallidum DNA purified from blood and T. pallidum strains isolated from blood or cerebrospinal fluid were analyzed for two 23S rDNA mutations and for the molecular targets used in an enhanced molecular stain typing system. Nine molecular strain types of T. pallidum were identified in Seattle from 2001 to 2010. Both macrolide resistance mutations were identified in Seattle strains, and the prevalence of resistant T. pallidum exceeded 80% in 2005 and increased through 2010. Resistance mutations were associated with discrete molecular strain types of T. pallidum. Macrolide-resistant T. pallidum strains are highly prevalent in Seattle, and each mutation is associated with discrete strain types. Macrolides should not be considered for treatment of syphilis in regions where prevalence of the mutations is high. Combining the resistance mutations with molecular strain typing permits a finer analysis of the epidemiology of syphilis in a community.

  20. Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified.

    Science.gov (United States)

    Read, Phillip; Tagg, Kaitlin A; Jeoffreys, Neisha; Guy, Rebecca J; Gilbert, Gwendolyn L; Donovan, Basil

    2016-08-01

    Strain typing of Treponema pallidum, using the three-target enhanced classification scheme, was performed with 191 samples obtained between 2004 and 2011 in Sydney, Australia. The most common strain type was 14d/g (92/191 samples [48%]). Two new TP0548 gene types were detected (m and n). Strain type was associated with macrolide resistance and possible acquisition outside Australia. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Solithromycin, a novel macrolide, does not prolong cardiac repolarization: a randomized, three-way crossover study in healthy subjects.

    Science.gov (United States)

    Darpo, Borje; Sager, Philip T; Fernandes, Prabhavathi; Jamieson, Brian D; Keedy, Kara; Zhou, Meijian; Oldach, David

    2017-02-01

    Macrolide antibiotics may cause QT prolongation. To study the QT effect of a novel macrolide, solithromycin. This was a thorough QT study with a three-way crossover design performed in healthy male and female subjects to evaluate the ECG effects of a novel macrolide, solithromycin. Forty-eight subjects were randomized to receive 800 mg of intravenous (iv) solithromycin, 400 mg of oral moxifloxacin and placebo in three separate treatment periods. Continuous 12 lead ECGs were recorded at a pre-dose baseline and serially after drug administration for 24 h. After the 40 min infusion of 800 mg of solithromycin, the geometric mean solithromycin peak plasma concentration (C max ) reached 5.9 (SD: 1.30) μg/mL. Solithromycin infusion caused a heart rate increase with a peak effect of 15 bpm immediately after the end of the infusion. The change-from-baseline QTcF (ΔQTcF) was similar after dosing with solithromycin and placebo and the resulting placebo-corrected ΔQTcF (ΔΔQTcF) for solithromycin was therefore small at all timepoints with a peak effect at 4 h of only 2.8 ms (upper bound of the 90% CI: 4.9 ms). Using a linear exposure-response model, a statistically significant, slightly negative slope of -0.86 ms per ng/mL (90% CI: -1.19 to -0.53; P = 0.0001) was observed with solithromycin. The study's ability to detect small QT changes was confirmed by the moxifloxacin response. Solithromycin did not have a clinically meaningful effect on the PR or QRS interval. The study demonstrated that solithromycin, unlike other macrolide antibiotics, does not cause QT prolongation. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against macrolide-resistant and -susceptible Mycoplasma genitalium strains.

    Science.gov (United States)

    Jensen, Jørgen Skov; Fernandes, Prabhavathi; Unemo, Magnus

    2014-06-01

    Mycoplasma genitalium has become well established as an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few M. genitalium strains are available to determine the MICs of currently used and new antimicrobial agents. Recent clinical trials have suggested that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, and alternative treatment with moxifloxacin is similarly under pressure from emerging resistance. Thus, there is an urgent need for new antimicrobials. The in vitro activity of the newly developed fluoroketolide solithromycin (CEM-101) was evaluated against a collection of 40 M. genitalium strains, including 15 with high-level macrolide resistance and 5 multidrug-resistant strains with resistance to both macrolides and quinolones. Furthermore, the MIC of solithromycin was correlated with mutations in the 23S rRNA gene and in the genes encoding ribosomal proteins L4 and L22. The in vitro results showed that solithromycin has activity against M. genitalium superior to that of other macrolides, doxycycline, and fluoroquinolones. Accordingly, this new fluoroketolide might be an effective option for treatment of M. genitalium infections. However, the efficacy of solithromycin in clinical trials with follow-up for test of cure and detection of genotypic and phenotypic resistance needs to be evaluated prior to widespread use. In a phase 2 clinical trial, solithromycin was highly effective as a single oral dose against C. trachomatis and Neisseria gonorrhoeae, suggesting that solithromycin could be a treatment option for several sexually transmitted infections, including in syndromic treatment of urethral and vaginal discharge. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. Emergence of Mycoplasma genitalium strains showing mutations associated with macrolide and fluoroquinolone resistance in the region Dresden, Germany.

    Science.gov (United States)

    Dumke, Roger; Thürmer, Alexander; Jacobs, Enno

    2016-10-01

    Among 323 specimens from male patients with symptoms of non-gonococcal urethritis, Mycoplasma genitalium was detected in 19 samples by real-time PCR. Mutations of 23S rRNA gene associated with macrolide resistance were confirmed in 10 strains. Amino acid changes at positions 81 and 83 of ParC protein were demonstrated indicating quinolone resistance of two strains. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The study of antimicrobial properties of immobilized fibrous N-chloro sulfonamides

    Directory of Open Access Journals (Sweden)

    V. N. Toropіn

    2016-12-01

    Full Text Available Aim. The determination of antibacterial and antifungal action of nonwoven form of N-chloro sulfonamides immobilized on a polypropylene fiber with a graft copolymer of styrene and divinylbenzene. Materials and methods. The object of the study was a non-woven form of sodium N-chloro sulfonamides immobilized on a polypropylene fiber with a graft copolymer of styrene and divinylbenzene. Determination of antibacterial and antifungal action of the material was carried out by the "agar plate" at the meat peptone agar (МPA. As the test cultures of microorganisms we used: E.coli, S.aureus and C.albicans. Microbial load was 1х107 TEM/ml. Results. The growing delay for such test microorganisms as E. coli strains, S.aureus and C.albicans fungi has been observed only for samples of material. Lack of microbial growth delay zones outside the samples occurs due to poor contact with the surface of the MPA. The method of "agar plate" has been changed to obtain reliable results of antibacterial and antifungal action of the material. The test material samples were placed in uncured MPA, the further experiment was carried out according to standard procedures of the "agar plates" method. Latency test microorganism growth around the sample material lies in the range 6,0 -7,0 mm – for E.coli; 16,0 -25,0 mm – for S.aureus; 4,0 -6,0 mm – for C.albicans. These results are explained by activation with the help of ammonium salts and amino acids, which release the active material of chlorine in case when the material contacts with the liquid nutrient medium. Evidently, this way the material will behave in contact with the skin of human (or animal. In contact with the dry skin covering the material will remain inactive, but in contact with the wound the release of active chlorine will occur within a specified period of time, whereby the material can protect the wound from infection. Conclusions. Antibacterial and antifungal properties of non-woven form of sodium N

  5. EFFICACY AND TOXICITY OF 2 DOSES OF TRIMETHOPRIM-SULFAMETHOXAZOLE AS PRIMARY PROPHYLAXIS AGAINST PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS

    NARCIS (Netherlands)

    SCHNEIDER, MME; NIELSEN, TL; NELSING, S; HOEPELMAN, AIM; SCHATTENKERK, JKME; VANDERGRAAF, Y; KOLSTERS, AFP; BORLEFFS, JCC; DANNER, SA; VANLEEUWEN, R; FRISSEN, JPHJ; WEIGEL, HM; VANDERENDE, IME; SPRENGER, HG; KAUFFMANN, RH; MEENHORST, PL; TENNAPEL, CHH; SCHREIJ, G; TENKATE, RW; JUTTMANN, [No Value; KOOPMANS, PP

    The efficacy and toxicity of trimethoprim-sulfamethoxazole (TMP-SMZ) as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with human immunodeficiency virus (HIV) infection was assessed by comparing the effects of two dosages (480 or 960 mg once a day) of the drug. The

  6. Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines.

    Science.gov (United States)

    Bennett, John M; Shapiro, Jonathan D; Choinski, Krystina N; Mei, Yingbin; Aulita, Sky M; Dominguez, Giovanny M; Majireck, Max M

    2018-01-03

    Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

  7. Role of the sulfonamide moiety of Ru(II) half-sandwich complexes in the asymmetric transfer hydrogenation of 3,4-dihydroisoquinolines

    Czech Academy of Sciences Publication Activity Database

    Matuška, O.; Zápal, J.; Hrdličková, R.; Mikoška, M.; Pecháček, J.; Vilhanová, B.; Václavík, Jiří; Kuzma, M.; Kačer, P.

    2016-01-01

    Roč. 118, č. 1 (2016), s. 215-222 ISSN 1878-5190 Institutional support: RVO:61388963 Keywords : ruthenium * asymmetric transfer hydrogenation * dihydroisoquinolines * sulfonamide Subject RIV: CC - Organic Chemistry Impact factor: 1.264, year: 2016

  8. Recent advances in sample preparation techniques and methods of sulfonamides detection - A review.

    Science.gov (United States)

    Dmitrienko, Stanislava G; Kochuk, Elena V; Apyari, Vladimir V; Tolmacheva, Veronika V; Zolotov, Yury A

    2014-11-19

    Sulfonamides (SAs) have been the most widely used antimicrobial drugs for more than 70 years, and their residues in foodstuffs and environmental samples pose serious health hazards. For this reason, sensitive and specific methods for the quantification of these compounds in numerous matrices have been developed. This review intends to provide an updated overview of the recent trends over the past five years in sample preparation techniques and methods for detecting SAs. Examples of the sample preparation techniques, including liquid-liquid and solid-phase extraction, dispersive liquid-liquid microextraction and QuEChERS, are given. Different methods of detecting the SAs present in food and feed and in environmental, pharmaceutical and biological samples are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Synthesis and pharmacological evaluation of novel phenyl sulfonamide derivatives designed as modulators of pulmonary inflammatory response.

    Science.gov (United States)

    Barbosa, Maria Letícia de Castro; Ramos, Thiago José Figueira; de Arantes, Ana Carolina Santos; Martins, Marco Aurélio; Silva, Patrícia Machado Rodrigues E; Barreiro, Eliezer J; Lima, Lídia Moreira

    2012-12-10

    In this paper we report the design, synthesis and pharmacological evaluation of a new series of phenyl sulfonamide derivatives 2a-h and 3-8 planned by structural modification on the anti-inflammatory prototype LASSBio-468 (1). Among the synthesized analogues, the tetrafluorophthalimide LASSBio-1439 (2e) stands out showing an in vitro anti-TNF-α effect similar to the standard thalidomide. The relevance of tetrafluorination of the phthalimide nucleus was also confirmed by the anti-inflammatory profile of 2e, through oral administration, in a murine model of pulmonary inflammation. The corresponding tetrafluorocarboxyamide metabolite LASSBio-1454 (15), generated from partial hydrolysis of the derivative 2e, presented a significant in vitro effect and a pronounced anti-inflammatory activity in vivo.

  10. Synthesis and in silico studies of novel sulfonamides having oxadiazole ring: As β-glucuronidase inhibitors.

    Science.gov (United States)

    Taha, Muhammad; Baharudin, Mohd Syukri; Ismail, Nor Hadiani; Selvaraj, Manikandan; Salar, Uzma; Alkadi, Khaled A A; Khan, Khalid Mohammed

    2017-04-01

    Novel sulfonamides having oxadiazole ring were synthesized by multistep reaction and evaluated to check in vitro β-glucuronidase inhibitory activity. Luckily, except compound 13, all compounds were found to demonstrate good inhibitory activity in the range of IC 50 =2.40±0.01-58.06±1.60μM when compared to the standard d-saccharic acid 1,4-lactone (IC 50 =48.4±1.25μM). Structure activity relationship was also presented. However, in order to ensure the SAR as well as the molecular interactions of compounds with the active site of enzyme, molecular docking studies on most active compounds 19, 16, 4 and 6 was carried out. All derivatives were fully characterized by 1 H NMR, 13 C NMR and EI-MS spectroscopic techniques. CHN analysis was also presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Distribution and accumulative pattern of tetracyclines and sulfonamides in edible vegetables of cucumber, tomato, and lettuce.

    Science.gov (United States)

    Ahmed, Mohamed Bedair M; Rajapaksha, Anushka Upamali; Lim, Jung Eun; Vu, Ngoc Thang; Kim, Il Seop; Kang, Ho Min; Lee, Sang Soo; Ok, Yong Sik

    2015-01-21

    Veterinary antibiotics can be released to environment by the animals' excretions, which thereby poses human health and ecological risks. Six antibiotics (tetracycline, oxytetracycline, chlortetracycline, sulfamethazine, sulfamethoxazole, and sulfadimethoxine) at three concentrations (5, 10, and 20 mg kg(-1) soil) were employed in pots filled with a loamy sand upland soil. Three types of vegetable seedlings, including cucumber (Cucumis sativus), cherry tomato (Solanum lycopersicum), and lettuce (Lactuca sativa), were also cultivated during 45 d in the greenhouse. All antibiotics taken up by tested plants showed negative effects on growth. Relatively high levels of tetracyclines and sulfonamides (SAs) were detected in the nonedible parts, roots, and leaves of cucumber and tomato, but fruit parts accumulated them lower than acceptable daily intake. Indeed, cucumber roots accumulated SAs by up to 94.6% of total addition (at 5 mg kg(-1) soil).

  12. Bacterial Synthesis of Unusual Sulfonamide and Sulfone Antibiotics by Flavoenzyme-Mediated Sulfur Dioxide Capture.

    Science.gov (United States)

    Baunach, Martin; Ding, Ling; Willing, Karsten; Hertweck, Christian

    2015-11-02

    Sulfa drugs, such as sulfonilamide and dapsone, are classical antibiotics that have been in clinical use worldwide. Despite the relatively simple architectures, practically no natural products are known to feature such aromatic sulfonamide or diarylsulfone substructures. We report the unexpected discovery of three fully unprecedented, sulfonyl-bridged alkaloid dimers (sulfadixiamycins A-C) from recombinant Streptomyces species harboring the entire xiamycin biosynthesis gene cluster. Sulfadixiamycins exhibit moderate antimycobacterial activities and potent antibiotic activities even against multidrug-resistant bacteria. Gene inactivation, complementation, and biotransformation experiments revealed that a flavin-dependent enzyme (XiaH) plays a key role in sulfadixiamycin biosynthesis. XiaH mediates a radical-based, three-component reaction involving two equivalents of xiamycin and sulfur dioxide, which is reminiscent of radical styrene/SO2 copolymerization. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

    Directory of Open Access Journals (Sweden)

    Hanmo Zhang

    2015-09-01

    Full Text Available Two new fates of imine intermediates formed on radical cyclizations of ene-sulfonamides have been identified, reduction and hydration/fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindoleanilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction, depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3-dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyloxindoles.

  14. Biochar based removal of antibiotic sulfonamides and tetracyclines in aquatic environments: A critical review.

    Science.gov (United States)

    Peiris, Chathuri; Gunatilake, Sameera R; Mlsna, Todd E; Mohan, Dinesh; Vithanage, Meththika

    2017-12-01

    Utilization of biochar (BC) as a low cost adsorbent for water remediation has gained an immense research interest due to their surface functionality and porosity. Although many reports on the BC based sorptive removal of Sulfonamides (SA) and Tetracyclines (TC) are available in literature, a deep insight into sorption mechanisms is yet to be reviewed. Objective of this review is to fill the research gap of a methodological understanding of sorption mechanisms and characteristics which is essential to develop efficient methods for contaminant removal. The most common adsorption mechanism can be considered as electron donor-acceptor interactions of electron withdrawing moieties with surface arene rings. The strongest adsorption of both antibiotics occurs at mildly acidic pH where the dominant species are zwitterionic or cationic. Smaller SAs exhibit micro pore-filling effects while bulky TCs experience size exclusions. Furthermore, the effect of matrix components and modifications are also been taken into account. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Inhibition of Dihydropteroate Synthetase from Escherichia coli by Sulfones and Sulfonamides

    Science.gov (United States)

    McCullough, Jerry L.; Maren, Thomas H.

    1973-01-01

    The inhibitory action of various diphenylsulfones and sulfonamides on dihydropteroate synthetase partially purified from Escherichia coli was examined. 4,4′-Diaminodiphenylsulfone (DDS; I50 = 2 × 10−5 M) and the monosubstituted derivatives 4-amino-4′-formamidodiphenylsulfone (I50 = 5.8 × 10−5 M) and 4-amino-4′-acetamidodiphenylsulfone (I50 = 5.2 × 10−5 M) were effective inhibitors of dihydropteroate synthetase activity. Disubstitution of the arylamine groups of DDS (4,4′-diformamidodiphenylsulfone and 4,4′-diacetamidodiphenylsulfone) resulted in complete loss of inhibitory activity. Both DDS (KI = 5.9 × 10−6 M) and sulfadiazine (KI = 2.5 × 10−6 M) were found to be competitive inhibitors of dihydropteroate synthetase. These findings are discussed in regard to the Bell and Roblin theory of structure-activity relationships for p-aminobenzoic acid antagonists. PMID:4597736

  16. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium (II) complexes

    KAUST Repository

    Jian, Zhongbao

    2014-12-08

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NHC6H3(2,6-R1,R2)]PdMe}2[A]2 (X1+-A: R1=R2=H: H1+-A; R1=R2=CH(CH3)2: DIPP1+-A; R1=H, R2=CF3: CF31+-A; A=BF4 or SbF6) and neutral palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NC6H3(2,6-R1,R2)]PdMe(L)} (X1-acetone: L=acetone; X1-dmso: L=dimethyl sulfoxide; X1-pyr: L=pyridine) chelated by a phosphine-sulfonamide were synthesized and fully characterized. Stoichiometric insertion of methyl acrylate (MA) into all complexes revealed that a 2,1 regiochemistry dominates in the first insertion of MA. Subsequently, for the cationic complexes X1+-A, β-H elimination from the 2,1-insertion product X2+-AMA-2,1 is overwhelmingly favored over a second MA insertion to yield two major products X4+-AMA-1,2 and X5+-AMA. By contrast, for the weakly coordinated neutral complexes X1-acetone and X1-dmso, a second MA insertion of the 2,1-insertion product X2MA-2,1 is faster than β-H elimination and gives X3MA as major products. For the strongly coordinated neutral complexes X1-pyr, no second MA insertion and no β-H elimination (except for DIPP2-pyrMA-2,1) were observed for the 2,1-insertion product X2-pyrMA-2,1. The cationic complexes X1+-A exhibited high catalytic activities for ethylene dimerization, affording butenes (C4) with a high selectivity of up to 97.7% (1-butene: 99.3%). Differences in activities and selectivities suggest that the phosphine-sulfonamide ligands remain coordinated to the metal center in a bidentate fashion in the catalytically active species. By comparison, the neutral complexes X1-acetone, X1-dmso, and X1-pyr showed very low activity towards ethylene to give traces of oligomers. DFT analyses taking into account the two possible coordination modes (O or N) of the sulfonamide ligand for the cationic system CF31+ suggested that the experimentally observed high activity in ethylene dimerization is the result of a facile first ethylene insertion into the O-coordinated PdMe isomer and

  17. Synthesis and Antimicrobial Activity of Bis-4,6-sulfonamidated 5,7-Dinitrobenzofuroxans

    Directory of Open Access Journals (Sweden)

    Irina V. Galkina

    2014-01-01

    Full Text Available A new series of bis-4,6-sulfonamidated 5,7-dinitrbenzofuroxans  7–11 had been synthesized and tested for antimicrobial activity. The structures of new sulfanilamide derivatives were characterized by elemental analysis, IR spectroscopy, and mass spectrometry (MALDITOF. The synthesized compounds were tested for their in vitro antimicrobial activity using the disk diffusion method against Gram-positive bacteria Staphylococcus aureus; the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis; the fungal strain Aspergillus niger; and the yeast-like pathogenic fungus Candida albicans. Our results indicate that the compounds 7–11 exhibit potent antimicrobial activity. The stability of the compounds was evaluated by TG and DSC methods.

  18. Quinoline- and isoquinoline-sulfonamide analogs of aripiprazole: novel antipsychotic agents?

    Science.gov (United States)

    Zajdel, Pawel; Partyka, Anna; Marciniec, Krzysztof; Bojarski, Andrzej J; Pawlowski, Maciej; Wesolowska, Anna

    2014-01-01

    The introduction of typical antipsychotics over six decades ago signaled an important milestone in psychiatry. However, second-generation antipsychotics ameliorated the positive symptoms of schizophrenia but displayed limited effectiveness for the negative and cognitive symptoms. In addition, while the newer antipsychotics produced fewer motor side effects, the atypical antipsychotics still induced weight gain and endocrinopathies. In recent years, a third generation of antipsychotics was identified. Aripiprazole was the first approved drug acting as a D2 partial agonist/functionally selective ligand. This review presents the state of the development of novel antipsychotic dopaminergic and non-dopaminergic agents, supported by an overview of the compounds evaluated under advanced preclinical and clinical development (e.g., cariprazine and brexpiprazole). In line with the recent trends in the development of modern atypical antipsychotics, we present our strategic development of long-chain arylpiperazine-derived quinoline- and isoquinoline-sulfonamide displaying a multireceptor binding profile and partial D2 receptor agonism.

  19. Does macrolide use confer risk of out-of-hospital cardiac arrest compared with penicillin V? A Danish national case-crossover and case-time-control study.

    Science.gov (United States)

    Hertz, Frederik Boetius; Jensen, Aksel; Knudsen, Jenny D; Arpi, Magnus; Andersson, Charlotte; Gislason, Gunnar H; Køber, Lars; Torp-Pedersen, Christian; Lippert, Freddy; Weeke, Peter E

    2018-02-23

    Macrolides have been associated with proarrhythmic properties, but the evidence is conflicting. We evaluated the risk of out-of-hospital cardiac arrest (OHCA) associated with specific macrolides in a retrospective study. Associations between specific macrolides and OHCA were examined by conditional logistic regression analyses in case-crossover and case-time-control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics. The present study was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)). We identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment. In the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0.97; 95% CI 0.74 to 1.26), erythromycin (OR=0.68; 95% CI 0.44 to 1.06), clarithromycin (OR=0.95; 95% CI 0.61 to 1.48) and azithromycin (OR=0.85; 95% CI 0.57 to 1.27).Similar results were obtained using case-time-control models: overall macrolide use (OR=0.81; 95% CI 0.62 to 1.06) and specific macrolides (roxithromycin ( OR=0.70; 95% CI 0.49 to 1.00), erythromycin ( OR=0.67; 95% CI 0.38 to 1.18), clarithromycin ( OR=0.75; 95% CI 0.41 to 1.39) or azithromycin ( OR=1.17; 95% CI 0.70 to 1.95)). The risk of OHCA during treatment with macrolides was similar to that of penicillin V, suggesting no additional risk of OHCA associated with macrolides. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. EFFECT OF MACROLIDE ANTIBIOTICS ON VARIOUS CELL CULTURES IN VITRO: 1. CELL MORPHOLOGY

    Directory of Open Access Journals (Sweden)

    Renáta Kováčová

    2012-08-01

    Full Text Available The aim of our study was to evaluate the cytotoxicity of macrolide antibiotics (tilmicosin, tylosin and spiramycin of various concentrations on different cell cultures in vitro. Cellular lines from animal tissues (VERO cells - kidney cells of Macacus rhesus, FE cells - feline embryonal cells, BHK 21 cellular line from young hamster kidneys were used. Tilmicosin effect: BHK cells are most sensitive, significant decrease in vital cells occurs already at the concentration of 50 μg.ml-1. VERO cells were most resistant, significant decrease of vital cells was observed only at the concentration of 300 μg.ml-1. Tylosin effect: BHK cells can be considered most sensitive, since at concentrations higher than 500 μg.ml-1, no vital cells were observed. At the concentration of 1000 μg.ml-1 were 3.13% of vital and 70.52% of subvital FE cells. In Vero cells, we observed a significant decrease at the concentration of 750 μg.ml-1. Spiramycin effect: Significant decrease of vital BHK cells was observed at the concentration of 150 μg.ml-1, at the concentration of 300 μg.ml-1, no vital cells and only 7.53% of subvital cells were observed. At the concentration of 500 μg.ml-1 reported 10.34% of vital FE cells. At the concentration of 500 μg.ml-1 22.48% of vital and 71.16% of subvital VERO cells were recorded.

  1. Structural Disorder in the Complex of Human Pregnane X Receptor and the Macrolide Antibiotic Rifampicin

    Energy Technology Data Exchange (ETDEWEB)

    Chrencik, Jill E.; Orans, Jillian; Moore, Linda B.; Xue, Yu; Peng, Li; Collins, Jon L.; Wisely, G. Bruce; Lambert, Millard H.; Kliewer, Steven A.; Redinbo, Matthew R. (U. of Texas-SMED); (UNC)

    2010-07-13

    The human nuclear xenobiotic receptor, pregnane X receptor (PXR), detects a variety of structurally distinct endogenous and xenobiotic compounds and controls expression of genes central to drug and cholesterol metabolism. The macrolide antibiotic rifampicin, a front-line treatment for tuberculosis, is an established PXR agonist and, at 823 Da, is one of the largest known ligands for the receptor. We present the 2.8 {angstrom} crystal structure of the ligand-binding domain of human PXR in complex with rifampicin. We also use structural and mutagenesis data to examine the origins of the directed promiscuity exhibited by the PXRs across species. Three structurally flexible loops adjacent to the ligand-binding pocket of PXR are disordered in this crystal structure, including the 200-210 region that is part of a sequence insert novel to the promiscuous PXRs relative to other members of the nuclear receptor superfamily. The 4-methyl-1-piperazinyl ring of rifampicin, which would lie adjacent to the disordered protein regions, is also disordered and not observed in the structure. Taken together, our results indicate that one wall of the PXR ligand-binding cavity can remain flexible even when the receptor is in complex with an activating ligand. These observations highlight the key role that structural flexibility plays in PXR's promiscuous response to xenobiotics.

  2. Structure-activity relationship studies on the macrolide exotoxin mycolactone of Mycobacterium ulcerans.

    Directory of Open Access Journals (Sweden)

    Nicole Scherr

    Full Text Available BACKGROUND: Mycolactones are a family of polyketide-derived macrolide exotoxins produced by Mycobacterium ulcerans, the causative agent of the chronic necrotizing skin disease Buruli ulcer. The toxin is synthesized by polyketide synthases encoded by the virulence plasmid pMUM. The apoptotic, necrotic and immunosuppressive properties of mycolactones play a central role in the pathogenesis of M. ulcerans. METHODOLOGY/PRINCIPAL FINDINGS: We have synthesized and tested a series of mycolactone derivatives to conduct structure-activity relationship studies. Flow cytometry, fluorescence microscopy and Alamar Blue-based metabolic assays were used to assess activities of mycolactones on the murine L929 fibroblast cell line. Modifications of the C-linked upper side chain (comprising C12-C20 caused less pronounced changes in cytotoxicity than modifications in the lower C5-O-linked polyunsaturated acyl side chain. A derivative with a truncated lower side chain was unique in having strong inhibitory effects on fibroblast metabolism and cell proliferation at non-cytotoxic concentrations. We also tested whether mycolactones have antimicrobial activity and found no activity against representatives of Gram-positive (Streptococcus pneumoniae or Gram-negative bacteria (Neisseria meningitis and Escherichia coli, the fungus Saccharomyces cerevisae or the amoeba Dictyostelium discoideum. CONCLUSION: Highly defined synthetic compounds allowed to unambiguously compare biological activities of mycolactones expressed by different M. ulcerans lineages and may help identifying target structures and triggering pathways.

  3. Detection of clindamycin susceptibility in macrolide resistant phenotypes of Staphylococcus Aureus

    Directory of Open Access Journals (Sweden)

    Goyal R

    2004-01-01

    Full Text Available The present study aimed at in vitro detection of macrolide resistant phenotypes of methicillin resistant Staphylococcus aureus (MRSA and interpretation of susceptibility tests to guide therapy. The study included 25 MRSA strains that were resistant to erythromycin and clindamycin, 25 MRSA strains that were sensitive to both erythromycin and clindamycin and 100 MRSA isolates which displayed erythromycin resistant but clindamycin susceptible phenotype. Erythromycin and clindamycin double disc susceptibility testing was done to detect inducible clindamycin resistance. Dilution susceptibility testing for clindamycin and erythromycin alone and in combination was performed for all 150 strains. Seventy-six strains showed blunting around clindamycin disc (inducible resistance. After induction with erythromycin, minimum inhibitory concentration (MIC of clindamycin was noticed to rise from atleast 16 to 256 g/mL in iMLSB phenotypes indicating inducible resistance. The detailed result analysis suggests the possible role of clindamycin in treatment of some of the erythromycin resistant isolates (non inducible, as there are multiplicity of resistance mechanisms and diversity of phenotypic expressions.

  4. Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter

    Science.gov (United States)

    Lu, Shuo; Zgurskaya, Helen I.

    2012-01-01

    Summary MacB is a founding member of the Macrolide Exporter family of transporters belonging to the ATP-Binding Cassette superfamily. These proteins are broadly represented in genomes of both gram-positive and gram-negative bacteria and are implicated in virulence and protection against antibiotics and peptide toxins. MacB transporter functions together with MacA, a periplasmic membrane fusion protein, which stimulates MacB ATPase. In gram-negative bacteria, MacA is believed to couple ATP hydrolysis to transport of substrates across the outer membrane through a TolC-like channel. In this study, we report a real-time analysis of concurrent ATP hydrolysis and assembly of MacAB-TolC complex. MacB binds nucleotides with a low millimolar affinity and fast on- and off-rates. In contrast, MacA-MacB complex is formed with a nanomolar affinity, which further increases in the presence of ATP. Our results strongly suggest that association between MacA and MacB is stimulated by ATP binding to MacB but remains unchanged during ATP hydrolysis cycle. We also found that the large periplasmic loop of MacB plays the major role in coupling reactions separated in two different membranes. This loop is required for MacA-dependent stimulation of MacB ATPase and at the same time, contributes to recruitment of TolC into a trans-envelope complex. PMID:23057817

  5. Heat treatment effects on the antimicrobial activity of macrolide and lincosamide antibiotics in milk.

    Science.gov (United States)

    Zorraquino, M A; Althaus, R L; Roca, M; Molina, M P

    2011-02-01

    Antibiotic residues in milk can cause serious problems for consumers and the dairy industry. Heat treatment of milk may diminish the antimicrobial activity of these antibiotic residues. This study analyzed the effect of milk processing (60 °C for 30 min, 120 °C for 20 min, and 140 °C for 10 s) on the antimicrobial activity of milk samples fortified with three concentrations of three macrolides (erythromycin: 20, 40 and 80 μg/liter; spiramycin: 100, 200, and 400 μg/liter; and tylosin: 500, 1,000, and 2,000 μg/liter) and one lincosamide (lincomycin: 1,000, 2,000, and 4,000 μg/liter). To measure the loss of antimicrobial activity, a bioassay based on the growth inhibition of Micrococcus luteus was done. The data were analyzed using a multiple linear regression model. The results indicate that treatment at 120 °C for 20 min produces inactivation percentages of 93% (erythromycin), 64% (spiramycin), 51% (tylosin), and 5% (lincomycin), while treatment at 140 °C for 10 s results in generally lower percentages (30% erythromycin, 35% spiramycin, 12% tylosin, and 5% lincomycin). The lowest loss or lowest reduction of antimicrobial activity (21% erythromycin and 13% spiramycin) was obtained by treatment at 60 °C for 30 min. Copyright ©, International Association for Food Protection

  6. Fluoroquinolone and macrolide resistance in Campylobacter jejuni isolated from broiler slaughterhouses in southern Brazil.

    Science.gov (United States)

    Sierra-Arguello, Yuli M; Perdoncini, G; Morgan, R B; Salle, C T P; Moraes, H L S; Gomes, Marcos J P; do Nascimento, Vladimir Pinheiro

    2016-01-01

    Campylobacter jejuni is recognized as a leading cause of acute bacterial gastroenteritis in humans. The over-use of antimicrobials in the human population and in animal husbandry has led to an increase in antimicrobial-resistant infections, particularly with fluoroquinolones and macrolides. The aim of the present study was to provide information of the current status of antimicrobial resistance patterns in Campylobacter jejuni from poultry sources. Fifty strains were recovered from broiler slaughterhouses in Rio Grande do Sul state, Brazil, 2012. The strains were investigated for antimicrobial susceptibility against three agents (ciprofloxacin, nalidixic acid and erythromycin) by minimal inhibitory concentrations. The strains were analysed by polymerase chain reaction-restriction fragment length polymorphism for detection of the Thr-86 mutation that confers resistance to ciprofloxacin. In addition, all the strains were tested for the presence of efflux systems (cmeB gene) conferring antimicrobial resistance. The minimum inhibitory concentrations results showed that 98% of isolates were sensitive to erythromycin and most isolates were resistant to ciprofloxacin (94%) and nalidixic acid (90%). A complete correlation was observed between the minimum inhibitory concentrations and PCR-RFLP assay. Finally, the cmeB gene that is responsible for multidrug resistance was detected in 16 isolates out the 50 strains (32%).

  7. Electrochemical degradation of sulfonamides at BDD electrode: Kinetics, reaction pathway and eco-toxicity evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Fabiańska, Aleksandra; Białk-Bielińska, Anna; Stepnowski, Piotr [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland); Stolte, Stefan [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland); UFT-Centre of Environmental Research and Sustainable Technology, University of Bremen, Leobener Straße UFT, D-28359 Bremen (Germany); Siedlecka, Ewa Maria, E-mail: ewa.siedlecka@ug.edu.pl [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland)

    2014-09-15

    Highlights: • SNs were electrochemically oxidized at BDD in one compartment reactor. • The efficiency of SN degradation was the highest in effluents from municipal WWTP. • The electro-degradation SNs based on oxidation but reduction was also possible. • Electrochemical oxidation of SNs led in some cases to mixtures toxic to L. minor. - Abstract: The investigation dealt with electrochemical oxidation of five sulfonamides (SNs): sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine (SMN) and sulfadimethoxine (SDM) in aqueous solution at boron-doped diamond (BDD) electrode. All studied sulfonamides were degraded according to a pseudo first order kinetics. The structure of SNs had no significant effect on the values of pseudo first order rate constants. Increased degradation efficiency was observed in higher temperature and in acidic pH. Due to the presence of chlorine and nitrate SNs were more effectively oxidized from municipal wastewater treatment plant (WWTP) effluents than from pure supporting electrolyte Na{sub 2}SO{sub 4}. The intermediates identified by LC–MS and GC–MS analysis suggested that the hydroxyl radicals attack mainly the S-N bond, but also the aromatic ring systems (aniline, pyrimidine or triazole) of SNs. Finally, the toxicity of the SNs solutions and effluents after electrochemical treatment was assessed through the measurement of growth inhibition of green algae (Scenedesmus vacualatus) and duckweed (Lemna minor). Toxicity of SMR, STZ, SMN solutions before and after electrochemical oxidation and SDM solution after the process in L. minor test was observed. No significant toxicity of studied SNs was observed in algae test.

  8. Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

    Directory of Open Access Journals (Sweden)

    Isabelle Karine da Costa Nunes

    Full Text Available Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448 presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral, 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma.

  9. Analytical approaches to the OH radical induced degradation of sulfonamide antibiotics in dilute aqueous solutions.

    Science.gov (United States)

    Sági, Gyuri; Csay, Tamás; Szabó, László; Pátzay, György; Csonka, Emil; Takács, Erzsébet; Wojnárovits, László

    2015-03-15

    By combining a large variety of analytical techniques this study aimed at elaborating methods to follow up the degradation of sulfonamides in an advanced oxidation process (AOP): irradiation with ionizing radiation in dilute aqueous solution. In this process, besides other radicals, hydroxyl radicals are produced. As pulse radiolysis experiments show the basic initial reaction is hydroxyl radical addition to the benzene ring, forming cyclohexadienyl radical intermediates. In aerated solutions these radicals transform to peroxy radicals. Among the first formed products aromatic molecules hydroxylated in the benzene rings or in some cases in the heterocyclic rings were observed by LC-MS/MS. Chemical oxygen demand (COD) measurements indicate that at the early reaction period of degradation one hydroxyl radical induces incorporation of 1.5 O atoms into the products. Comparison of the COD and TOC (total organic carbon content) results shows gradual oxidation. Simultaneously with hydroxylation ring opening also takes place. The kinetics of inorganic SO4(2-) and NH4(+) formation, analyzed by ion chromatography, is similar to the kinetics of ring degradation (UV spectroscopy), however, there is a delayed formation of NO3(-). The latter ions may be produced in oxidative degradation of smaller N containing fragments. The S atoms of the sulfonamides remain in the solution (ICP-MS measurements) after degradation, whereas some part of the N atoms leaves the solution probably in the form of N2 (total nitrogen content (TN) measurements). Degradation is accompanied by a high pH drop due to formation of SO4(2-), NO3(-) and smaller organic acids. The degradation goes through many simultaneous and consecutive reactions, and with the applied methods the different stages of degradation can be characterized. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Mycoplasma genitalium in five cities in Russia and Estonia.

    Science.gov (United States)

    Shipitsyna, Elena; Rumyantseva, Tatiana; Golparian, Daniel; Khayrullina, Guzel; Lagos, Amaya C; Edelstein, Inna; Joers, Kai; Jensen, Jörgen S; Savicheva, Alevtina; Rudneva, Natalia; Sukhanova, Larisa; Kozlov, Roman; Guschin, Alexander; Unemo, Magnus

    2017-01-01

    Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking. The aim of this study was to estimate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium in four cities in Russia and one in Estonia, 2013-2016. Consecutive urogenital samples found positive for M. genitalium during diagnostic testing were retrospectively analyzed for resistance-associated mutations in the 23S rRNA and parC genes using pyrosequencing and conventional Sanger sequencing, respectively. In total, 867 M. genitalium positive samples from 2013-2016 were analyzed. Macrolide resistance-associated mutations were detected in 4.6% of the samples from Russia (0.7-6.8% in different cities) and in 10% of the samples from Estonia. The mutations A2059G and A2058G were highly predominating in both Russia and Estonia, accounting together for 90.9% of the cases positive for nucleotide substitutions in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated mutations were 6.2% in Russia (2.5-7.6% in different cities) and 5% in Estonia. The mutations S83I and S83N were the most frequent ones in Russia (24.4% each), whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone resistance-associated mutations). Approximately 1% of the samples in both countries harbored both macrolide and possible fluoroquinolone resistance-associated mutations, with A2058G and S83I being the most frequent combination (37.5%). The prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia, and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of macrolide and fluoroquinolone resistance in these countries, antimicrobial resistance

  11. Synthesis, structure, and properties of compounds with a chalcogen-nitrogen bond. VIII. N-sulfonylaryltellurimides - effective catalysts for the condensation of aromatic aldehydes with sulfonamides

    Energy Technology Data Exchange (ETDEWEB)

    Naddaka, V.I.; Anavesyan, K.V.; Cherkinskaya, M.L.; Minkin, V.I.

    1988-08-20

    N-Sulfonyldiaryltellurimides and diaryl telluroxides are effective catalysts in the synthesis of N-sulfonylazomethines from aromatic aldehydes and sulfonamides. The catalytic activity of these compounds in the investigated. The reaction is based on the reaction of the aromatic aldehydes with the N-sulfonyldiaryltellurimides, leading to the formation of N-sulfonylazomethines and diaryl telluroxides. The latter in turn react with the sulfonamides, giving the tellurimides, and this gives rise to the cyclic nature of the processes.

  12. Rapid trace level determination of sulfonamide residues in honey with online extraction using short C-18 column by high-performance liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Sajid, Muhammad; Na, Na; Safdar, Muhammad; Lu, Xin; Ma, Lin; He, Lan; Ouyang, Jin

    2013-11-01

    A sensitive and inexpensive quantification method with online extraction using a short C-18 column for sulfonamide residues in honey by high performance liquid chromatography with fluorescence detector was developed and validated. In sample preparation, acid hydrolysis was used to break the N-glycoside bond between the honey sugar and sulfonamide drugs and derivatization of sulfonamide residues with fluorescamine was conducted at pH 3.5 using a citrate buffer (0.5M) in the honey matrix. The chromatography was carried out on Zorbax Extended C-18 (250mm×4.6mm; 5μm) column, using a mixture of acetonitrile and an acetate buffer (pH 4.50, 20mM) as a mobile phase. A Zorbax Extended C-18 (12mm×4.6mm; 5μm) column was used for online extraction of fifteen sulfonamide residues from honey sample with the help of a two position valve. The limit of quantification of sulfonamide residues in honey was less than 3ngg(-1), and the percentage recovery of study compounds in spiked honey sample was from 80% for sulfacetamide to 100% of sulfachloropyridazine. The developed method has excellent linearity for all studied sulfonamides with a correlation coefficient 0.993. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Automated Online Solid-Phase Extraction Coupled with Sequential Injection-HPLC-EC System for the Determination of Sulfonamides in Shrimp

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    Pimkwan Chantarateepra

    2012-01-01

    Full Text Available The use of fully automated online solid-phase extraction (SPE coupled with sequential injection analysis, high-performance liquid chromatography (HPLC, and electrochemical detection (EC for the separation and determination of sulfonamides has been developed. A homemade microcolumn SPE system coupled with sequential injection analysis (SIA was used to automate the sample cleanup and extraction of sulfonamides. The optimal flow rate of sample loading and elution was found to be 10 μL/s, and optimal elution time of zone was 20–24 s. Under the optimal conditions, a linear relationship between peak area and sulfonamide concentrations was obtained in the range of 0.01–8.0 μg mL−1. Detection limits for seven sulfonamides were between 1.2 ng mL−1 and 11.2 ng mL−1. The proposed method has been applied for the determination of sulfonamides in shrimp. Recoveries in the range of 84–107% and relative standard deviations (RSDs below 6.5% for intraday and 13% for inter-day were received for three concentration levels of spiking. The results showed that the present method was simple, rapid, accurate and highly sensitive for the determination of sulfonamides.

  14. Comprehensive determination of macrolide antibiotics, their synthesis intermediates and transformation products in wastewater effluents and ambient waters by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Senta, Ivan; Krizman-Matasic, Ivona; Terzic, Senka; Ahel, Marijan

    2017-08-04

    Macrolide antibiotics are a prominent group of emerging contaminants frequently found in wastewater effluents and wastewater-impacted aquatic environments. In this work, a novel analytical method for simultaneous determination of parent macrolide antibiotics (azithromycin, erythromycin, clarithromycin and roxithromycin), along with their synthesis intermediates, byproducts, metabolites and transformation products in wastewater and surface water was developed and validated. Samples were enriched using solid-phase extraction on Oasis HLB cartridges and analyzed by reversed-phase liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The target macrolide compounds were separated on an ACE C18 PFP column and detected using multiple reaction monitoring in positive ionization polarity. The optimized method, which included an additional extract clean-up on strong anion-exchange cartridges (SAX), resulted in high recoveries and accuracies, low matrix effects and improved chromatographic separation of the target compounds, even in highly complex matrices, such as raw wastewater. The developed method was applied to the analysis of macrolide compounds in wastewater and river water samples from Croatia. In addition to parent antibiotics, several previously unreported macrolide transformation products and/or synthesis intermediates were detected in municipal wastewater, some of them reaching μg/L levels. Moreover, extremely high concentrations of macrolides up to mg/L level were found in pharmaceutical industry effluents, indicating possible importance of this source to the total loads into ambient waters. The results revealed a significant contribution of synthesis intermediates and transformation products to the overall mass balance of macrolides in the aquatic environment. Copyright © 2017. Published by Elsevier B.V.

  15. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

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    Carolina Ribeiro E Silva

    Full Text Available Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenylprop-2-enoyl]phenyl} benzenesulfonamide (CPN were assessed using the Salmonella typhimurium reverse mutation test (Ames test and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05. The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p 0.05. Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

  16. Inhibition of the α-carbonic anhydrase from Vibrio cholerae with amides and sulfonamides incorporating imidazole moieties.

    Science.gov (United States)

    De Vita, Daniela; Angeli, Andrea; Pandolfi, Fabiana; Bortolami, Martina; Costi, Roberta; Di Santo, Roberto; Suffredini, Elisabetta; Ceruso, Mariangela; Del Prete, Sonia; Capasso, Clemente; Scipione, Luigi; Supuran, Claudiu T

    2017-12-01

    We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The secondary sulfonamides and amides investigated here were potent, low nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment.

  17. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test

    Science.gov (United States)

    Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo e

    2015-01-01

    Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties. PMID:26335560

  18. Prevalence of Genotypes That Determine Resistance of Staphylococci to Macrolides and Lincosamides in Serbia

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    Milena Mišić

    2017-08-01

    Full Text Available Macrolides, lincosamides, and streptogramins (MLS resistance genes are responsible for resistance to these antibiotics in Staphylococcus infections. The purpose of the study was to analyze the distribution of the MLS resistance genes in community- and hospital-acquired Staphylococcus isolates. The MLS resistance phenotypes [constitutive resistance to macrolide–lincosamide–streptogramin B (cMLSb, inducible resistance to macrolide–lincosamide–streptogramin B (iMLSb, resistance to macrolide/macrolide–streptogramin B (M/MSb, and resistance to lincosamide–streptogramin A/streptogramin B (LSa/b] were determined by double-disc diffusion method. The presence of the MLS resistance genes (ermA, ermB, ermC, msrA/B, lnuA, lnuB, and lsaA were determined by end-point polymerase chain reaction in 179 isolates of staphylococci collected during 1-year period at the Center for Microbiology of Public Health Institute in Vranje. The most frequent MLS phenotype among staphylococcal isolates, both community-acquired and hospital-acquired, was iMLSb (33.4%. The second most frequent was M/MSb (17.6% with statistically significantly higher number of hospital-acquired staphylococcal isolates (p < 0.05. MLS resistance was mostly determined by the presence of msrA/B (35.0% and ermC (20.8% genes. Examined phenotypes were mostly determined by the presence of one gene, especially by msrA/B (26.3% and ermC (14.5%, but 15.6% was determined by a combination of two or more genes. M/MSb phenotype was the most frequently encoded by msrA/B (95.6% gene, LSa/b phenotype by lnuA (56.3% gene, and iMLSb phenotype by ermC (29.4% and ermA (25.5% genes. Although cMLSb phenotype was mostly determined by the presence of ermC (28.9%, combinations of two or more genes have been present too. This pattern was particularly recorded in methicillin-resistant Staphylococcus aureus (MRSA (58.3% and methicillin-resistant coagulase-negative staphylococci (MRCNS (90.9% isolates with c

  19. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS: Study protocol for a randomised controlled trial

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    Uzun Sevim

    2012-06-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. Methods/design The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. Discussion We investigate whether

  20. Rh(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides using activated and unactivated alkenes.

    Science.gov (United States)

    Li, Xuting; Gong, Xue; Zhao, Miao; Song, Guoyong; Deng, Jian; Li, Xingwei

    2011-11-04

    Rhodium(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides has been achieved at the peri position. Three categories of olefins have been successfully applied. Activated olefins reacted to afford five-membered azacycles as a result of oxidative olefination-hydroamination. Unactivated olefins reacted to give the olefination product. 2-fold oxidative C-C and C-N coupling was achieved for allylbenzenes. © 2011 American Chemical Society

  1. Intermolecular sulfenoamination of alkenes with sulfonamides and N-sulfanylsuccinimides to access β-sulfonylamino sulfides and dihydrobenzothiazines.

    Science.gov (United States)

    Liu, Tao; Tian, Jun; Gao, Wen-Chao; Chang, Hong-Hong; Liu, Qiang; Li, Xing; Wei, Wen-Long

    2017-07-19

    An acid-catalyzed intermolecular sulfenoamination reaction of alkenes is developed with sulfonamides as the nitrogen source and N-sulfanylsuccinimides as the sulfur source. This methodology provides a straightforward and general way to synthesize various β-sulfonylamino sulfides with high regio- and diastereoselectivity. The developed method was coupled with intramolecular C-N coupling in a one-pot procedure to afford a series of dihydrobenzothiazine derivatives, a kind of important heterocycle used as biologically active compounds in medicinal chemistry.

  2. EFFECT OF MACROLIDE ANTIBIOTICS ON VARIOUS CELL CULTURES IN VITRO: 2. CELL BIOCHEMISTRY

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    Anton Kováčik

    2012-12-01

    Full Text Available he aim of our study was to evaluate the effect of macrolide antibiotics (tilmicosin, tylosin and spiramycin on the cellular biochemistry using different cell cultures in vitro. Cellular lines from animal tissues (VERO cells - kidney cells of Macacus Rhesus, FE cells - feline embryonal cells and BHK21 - cellular line from young hamster kidneys were used. The effect was assessed after 24 hours of culture. We studied the concentration of calcium (Ca, magnesium (Mg, sodium (Na, potassium (K, chlorides (Cl, total proteins (TP and cholesterol (Chol. Biochemical analysis of BHK21 cells cultivated with tilmicosin showed a significant decrease in the concentration of Ca, Cl and TP in almost all experimental groups. No significant differences were found in the FE cells. The highest concentrations of tilmicosin led to a significant increase of all analyzed elements and TP in medium in the VERO cells. The effect of tylosin on the BHK21 cell metabolism showed a significant decrease in the concentration of Na and Cl in the all experimental groups and a significant decrease in the concentration of TP in the groups to which more than 700 µg.ml-1 was added. No significant differences were found in the FE and VERO cells. Biochemical analysis of BHK21 cells with spyramicin showed a significant decrease in the concentration of Na in the all experimental groups and a significant decrease in the concentration of Cl and TP in the cell cultures with 100 µg.ml-1, 150 µg.ml-1, 200 µg.ml-1, 300 µg.ml-1 concentrations of spyramycin. The highest concentrations of spyramycin caused a significant increase of Na and a significant decrease of Chol in the FE cells. No significant differences were found in the VERO cells except increased total proteins at the highest concentration of spyramycin.

  3. Semisynthetic macrolide antibacterials derived from tylosin. Synthesis and structure-activity relationships of novel desmycosin analogues.

    Science.gov (United States)

    Mutak, Stjepan; Marsić, Natasa; Kramarić, Miroslava Dominis; Pavlović, Drazen

    2004-01-15

    A series of 20-O-substituted and 3,20-di-O-substituted derivatives of desmycosin were synthesized and their biological properties were evaluated. In particular, we have synthesized numerous side chain modified analogues of desmycosin as well as some analogues possessing a combination of modified side chain and alternative C-3 substituents. Thus, alpha,beta-unsaturated analogues of desmycosin (2), tylosin (1), 10,11,12,13-tetrahydrotylosin (11), and 2,3-didehydrodesmycosin (13) were prepared from the corresponding aldehydes by a Wittig reaction with the stabilized ylides (a-d), generating a trans-double bond, followed by modified Pfitzner-Moffat oxidation of the C-3 hydroxyl group. To evaluate the importance of the C-3 position of desmycosin for biological activity, the C-3 substituted derivatives were synthesized by a standard sequence of protective group chemistry followed by Wittig reaction and esterification as the key steps. For the attachment of the C-3 ester functionality, a mixed anhydride protocol was adopted. Reaction proceeded smoothly to give corresponding esters in yields ranging from 70 to 80%. Base- and acid-catalyzed rearrangement products including desmycosin 8,20-aldols (24a and 24b) and desmycosin 3,19-aldol (25) are also described. Parallel array synthesis and purification techniques allowed for the rapid exploration of structure-activity relationships within this class and for the improvement in potency. In vitro evaluation of these derivatives demonstrated good antimicrobial activity against Gram-positive bacteria for most of the compounds. The present derivatives of 16-membered macrolides were active against MLS(B)-resistant strains that were inducibly resistant, but not those constitutively resistant to erythromycin.

  4. Detection of macrolide and disinfectant resistance genes in clinical Staphylococcus aureus and coagulase-negative staphylococci

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    Bakhrouf Amina

    2011-10-01

    Full Text Available Abstract Background Staphylococcus aureus and Coagulase-negative staphylococci (CoNS are a major source of infections associated with indwelling medical devices. Many antiseptic agents are used in hygienic handwash to prevent nosocomial infections by Staphylococci. Our aim was to determine the antibiotic susceptibility and resistance to quaternary ammonium compound of 46 S. aureus strains and 71 CoNS. Methods S. aureus (n = 46 isolated from auricular infection and CoNS (n = 71, 22 of the strains isolated from dialysis fluids and 49 of the strains isolated from needles cultures were investigated. Erythromycin resistance genes (ermA, ermB, ermC, msrA and mef were analysed by multiplex PCR and disinfectant-resistant genes (qacA, qacB, and qacC were studied by PCR-RFLP. Results The frequency of erythromycin resistance genes in S. aureus was: ermA+ 7.7%, ermB+ 13.7%, ermC+ 6% and msrA+ 10.2%. In addition, the number of positive isolates in CoNS was respectively ermA+ (9.4%, ermB+ (11.1%, ermC+ (27.4%, and msrA+ (41%. The MIC analyses revealed that 88 isolates (74% were resistant to quaternary ammonium compound-based disinfectant benzalkonium chloride (BC. 56% of the BC-resistant staphylococcus isolates have at least one of the three resistant disinfectants genes (qacA, qacB and qacC. Nine strains (7.7% among the CoNS species and two S. aureus strains (2% harboured the three-qac genes. In addition, the qacC were detected in 41 strains. Conclusions Multi-resistant strains towards macrolide and disinfectant were recorded. The investigation of antibiotics and antiseptic-resistant CoNS may provide crucial information on the control of nosocomial infections.

  5. Detection of Macrolide, Lincosamide and Streptogramin Resistance among Methicillin Resistant Staphylococcus aureus (MRSA in Mumbai

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    Arunagiri Subramanian

    2015-01-01

    Full Text Available Background: The increase in incidence of Methicillin Resistant Staphyloccocus aureus (MRSA and its extraordinary potential to develop antimicrobial resistance has highlighted the need for better agents to treat such infections. This has led to a renewed interest in use of new drugs for treatment with clindamycin and quinuprsitin-dalfopristin being the preferred choice for treatment. Aim & Objectives: This study was undertaken to detect the prevalence of MacrolideLincosamide-Streptogramin (MLS resistance among clinical isolates of MRSA.Material and Methods:Two hundred and thirty clinical isolates of S. aureus were subjected to routine antibiotic susceptibility testing including cefoxitin, erythromycin and quinupristindalfopristin. Inducible resistance to clindamycin was tested by 'D' test as per Clinical and Laboratory Standards Institute (CLSI guidelines. Results: Out of all S. aureus isolates, 93.91% were identified as MRSA. In the disc diffusion testing, 81.5% of isolates showed erythromycin resistance. Among these, the prevalence of constitutive (cMLS , inducible (iMLS b b and MS-phenotype were 35.80%, 31.82% and 32.39% respectively by the D-test method. 77.8% of isolates were resistant to quinupristin-dalfopristin and the Minimum Inhibitory Concentration (MIC ranged from 4–32 µg/ml. 89.20% of isolates were resistant to both quinupristin-dalfopristin and erythromycin of which 35.03%, 35.67% and 29.30% belonged to iMLS , cMLS and MS phenotype respectively. Conclusion: The emergence of quinupristindalfopristin resistance and MLS phenotypes brings b about the need for the simple and reliable D-test in routine diagnosis and further susceptibility testing for proper antimicrobial therapy.

  6. Molecular Typing and Macrolide Resistance of Syphilis Cases in Manitoba, Canada, From 2012 to 2016.

    Science.gov (United States)

    Shuel, Michelle; Hayden, Kristy; Kadkhoda, Kamran; Tsang, Raymond S W

    2018-04-01

    The province of Manitoba, Canada, with a population of approximately 1.3 million, has been experiencing increased incidence of syphilis cases since 2015. In this study, we examined the detection of Treponema pallidum DNA in 354 clinical samples from 2012 to 2016, and determined molecular types and mutations conferring resistance to azithromycin in the polymerase chain reaction (PCR)-positive samples. T. pallidum DNA detection was done by PCR amplification of tpp47, bmp, and polA genes. Syphilis serology results were reviewed for the PCR-positive cases. Molecular typing of syphilis strains was done by analysis of the T, pallidum arp, tpr, and tp0548 gene targets as well as partial sequencing of the 23S rRNA gene for azithromycin resistance. Of the 354 samples tested, 74 individual cases were PCR positive. A result from the treponemal antibody chemiluminescent microparticle immunoassay test was positive in 72 of these cases and that from the Venereal Disease Research Laboratory testing was positive in 66. Mutations conferring resistance to azithromycin were found in all 74 PCR-positive samples. Molecular typing was completed on 57 PCR-positive samples, and 12 molecular types were identified with 14d/g found in 63.2%. Increased strain diversity was observed with 8 molecular types detected in 2016, whereas only 2 to 3 types were found in 2012 to 2014. A patient with 2 episodes of infection 9 months apart caused by different molecular strain types was also identified. The finding of an increase in genetic diversity in the strains in this study and an increase in macrolide resistance compared with previous Canadian reports highlighted the need for continued surveillance including strain characterization.

  7. The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures

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    Alejandro Castro-Alvarez

    2017-01-01

    Full Text Available The accuracy of five docking programs at reproducing crystallographic structures of complexes of 8 macrolides and 12 related macrocyclic structures, all with their corresponding receptors, was evaluated. Self-docking calculations indicated excellent performance in all cases (mean RMSD values ≤ 1.0 and confirmed the speed of AutoDock Vina. Afterwards, the lowest-energy conformer of each molecule and all the conformers lying 0–10 kcal/mol above it (as given by Macrocycle, from MacroModel 10.0 were subjected to standard docking calculations. While each docking method has its own merits, the observed speed of the programs was as follows: Glide 6.6 > AutoDock Vina 1.1.2 > DOCK 6.5 >> AutoDock 4.2.6 > AutoDock 3.0.5. For most of the complexes, the five methods predicted quite correct poses of ligands at the binding sites, but the lower RMSD values for the poses of highest affinity were in the order: Glide 6.6 ≈ AutoDock Vina ≈ DOCK 6.5 > AutoDock 4.2.6 >> AutoDock 3.0.5. By choosing the poses closest to the crystal structure the order was: AutoDock Vina > Glide 6.6 ≈ DOCK 6.5 ≥ AutoDock 4.2.6 >> AutoDock 3.0.5. Re-scoring (AutoDock 4.2.6//AutoDock Vina, Amber Score and MM-GBSA improved the agreement between the calculated and experimental data. For all intents and purposes, these three methods are equally reliable.

  8. Sulfonamide-Resistant Bacteria and Their Resistance Genes in Soils Fertilized with Manures from Jiangsu Province, Southeastern China

    Science.gov (United States)

    Jiao, Shaojun; Zhang, Jun; Ye, Boping; Gao, Shixiang

    2014-01-01

    Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of antibiotic resistance genes (ARGs) increasingly in the soil. The frequency of sulfonamide resistance genes was sul1 > sul2 > sul3 in pig-manured soil DNA and sul2 > sul1 > sul3 in chicken-manured soil DNA. Further analysis suggested that the frequency distribution of the sul genes in the genomic DNA and plasmids of the SR isolates from manured soil was sul2 > sul1 > sul3 overall (panimal type and sampling time can influence the prevalence and distribution pattern of sulfonamide resistance genes. The present study also indicated that Bacillus, Pseudomonas and Shigella were the most prevalent sul-positive genera in the soil, suggesting a potential human health risk. The above results could be important in the evaluation of antibiotic-resistant bacteria and genes from manure as sources of agricultural soil pollution; the results also demonstrate the necessity and urgency of the regulation and supervision of veterinary antibiotics in China. PMID:25405870

  9. Application of liquid chromatography-electrospray ionization tandem mass spectrometry to the detection of 10 sulfonamides in honey.

    Science.gov (United States)

    Verzegnassi, L; Savoy-Perroud, M C; Stadler, R H

    2002-11-15

    Liquid chromatography (LC) in combination with tandem mass spectrometry (MS-MS) has been applied to the separation and detection of 10 different sulfonamides in honey. The methodology encompasses a simple hydrolysis of the honey sample to liberate sugar-bound sulfonamides followed by liquid-liquid extraction of the 10 analytes, filtration, and analysis by LC-MS-MS. Conditions for reversed-phase LC and electrospray ionization (ESI) MS-MS in the positive ion mode were optimized for the 10 compounds under study, monitoring two characteristic mass transitions simultaneously for each analyte. The procedure is a qualitative confirmatory method for 10 sulfonamides at the low microg/kg level in honey. Typical recoveries of the analytes in honey ranged from 44 to 73% at a fortification level of 50 microg/kg. This study also addresses the issue of matrix-induced suppression of ionization, an effect often encountered in trace residue analysis of food matrices using LC-ESI-MS-MS based methods.

  10. Conformer-Specific IR Spectroscopy of Laser-Desorbed Sulfonamide Drugs: Tautomeric and Conformational Preferences of Sulfanilamide and its Derivatives

    Science.gov (United States)

    Uhlemann, Thomas; Seidel, Sebastian; Müller, Christian W.

    2017-06-01

    Molecules containing the sulfonamide group R^{1}-SO_2-NHR^{2} have a longstanding history as antimicrobial agents. Even though nowadays they are not commonly used in treating humans anymore, they continue to be studied as effective inhibitors of metalloenzyme carbonic anhydrases. These enzymes are important targets for a variety of diseases, such as, for instance, breast cancer, glaucoma, and obesity. Here we present the results of our laser desorption single-conformation UV and IR study of sulfanilamide (NH_2Ph-SO_2-NHR, R=H), a variety of singly substituted derivatives, and their monohydrated complexes. Depending on the substituent, the sulfonamide group can either adopt an amino or an imino tautomeric form. The form prevalent in the crystal is not necessarily also the tautomeric form we identified in the molecular beam after laser desorbing the sample. Furthermore, we explored the effect of complexation with a single water molecule on the tautomeric and conformational preferences of the sulfonamides. Our conformer-specific IR spectra in the NH and OH stretch region (3200-3750 \\wn) suggest that the intra- and intermolecular interactions governing the structures of the monomers and water complexes are surprisingly diverse. We have undertaken both Quantum Theory of Atoms in Molecules (QTAIM) and Interacting Quantum Atoms (IQA) analyses of calculated electron densities to quantitatively characterize the nature and strengths of the intra- and intermolecular interactions prevalent in the monomer and water complex structures.

  11. Imaging of CA IX with fluorescent labelled sulfonamides distinguishes hypoxic and (re)-oxygenated cells in a xenograft tumour model

    International Nuclear Information System (INIS)

    Dubois, Ludwig; Lieuwes, Natasja G.; Maresca, Alfonso; Thiry, Anne; Supuran, Claudiu T.; Scozzafava, Andrea; Wouters, Bradly G.; Lambin, Philippe

    2009-01-01

    Background and purpose: Carbonic anhydrase (CA) IX is suggested to be an endogenous marker of hypoxia. Fluorescent sulfonamides with a high affinity for CA IX (CAI) have been developed and shown to bind to cells only when CA IX protein was expressed and while cells were hypoxic. The aim of this study was to investigate the in vivo CAI binding properties in a xenograft tumour model using fluorescent imaging. Materials and methods: NMRI-nu mice subcutaneously transplanted with HT-29 colorectal tumours were treated with 7% oxygen or with nicotinamide and carbogen and were compared with control animals. CAI accumulation was monitored by non-invasive fluorescent imaging. Results: Specific CAI accumulation could be observed in delineated tumour areas as compared with a non-sulfonamide analogue (P < 0.01). Administration of nicotinamide and carbogen, decreasing acute and chronic hypoxia, respectively, prevented CAI accumulation (P < 0.05). When treated with 7% oxygen breathing, a 3-fold higher CAI accumulation (P < 0.01) was observed. Furthermore, the bound CAI fraction was rapidly reduced upon tumour reoxygenation (P < 0.01). Conclusions: Our in vivo imaging results confirm previous in vitro data demonstrating that CAI binding and retention require exposure to hypoxia. Fluorescent labelled sulfonamides provide a powerful tool to visualize hypoxia response. An important step is made towards clinical applicability, indicating the potential of patient selection for CA IX-directed therapies.

  12. Discovery of dehydroabietic acid sulfonamide based derivatives as selective matrix metalloproteinases inactivators that inhibit cell migration and proliferation.

    Science.gov (United States)

    Huang, Ri-Zhen; Liang, Gui-Bin; Huang, Xiao-Chao; Zhang, Bin; Zhou, Mei-Mei; Liao, Zhi-Xin; Wang, Heng-Shan

    2017-09-29

    A series of dehydroabietic acid (DHAA) dipeptide derivatives containing the sulfonamide moiety were designed, synthesized and evaluated for inhibition of MMPs as well as the effects of in vitro cell migration. These compounds exhibited relatively good inhibition activity against MMPs with IC 50 values in low micromolar range. A docking study of the most active compound 8k revealed key interactions between 8k and MMP-3 in which the sulfonamide moiety and the dipeptide group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU. In particular, compound 8k appeared to be the most potent compound against the HepG2 cell line, at least partly, by inhibition of the activity of MMP-3 and apoptosis induction. The treatment of HepG2 cells with compound 8k resulted in inhibition of in vitro cell migration through wound healing assay and G1 phase of cell cycle arrested. In addition, 8k-induced apoptosis was significantly facilitated in HepG2 cells. Thus, we conclude that DHAA dipeptide derivatives containing the sulfonamide moiety may be the potential MMPs inhibitors with the ability to suppress cells migration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Determination of sulfonamides in butter samples by ionic liquid magnetic bar liquid-phase microextraction high-performance liquid chromatography.

    Science.gov (United States)

    Wu, Lijie; Song, Ying; Hu, Mingzhu; Xu, Xu; Zhang, Hanqi; Yu, Aimin; Ma, Qiang; Wang, Ziming

    2015-01-01

    A novel, simple, and environmentally friendly pretreatment method, ionic liquid magnetic bar liquid-phase microextraction, was developed for the determination of sulfonamides in butter samples by high-performance liquid chromatography. The ionic liquid magnetic bar was prepared by inserting a stainless steel wire into the hollow of a hollow fiber and immobilizing ionic liquid in the micropores of the hollow fiber. In the extraction process, the ionic liquid magnetic bars were used to stir the mixture of sample and extraction solvent and enrich the sulfonamides in the mixture. After extraction, the analyte-adsorbed ionic liquid magnetic bars were readily isolated with a magnet from the extraction system. It is notable that the present method was environmentally friendly since water and only several microliters of ionic liquid were used in the whole extraction process. Several parameters affecting the extraction efficiency were investigated and optimized, including the type of ionic liquid, sample-to-extraction solvent ratio, the number of ionic liquid magnetic bars, extraction temperature, extraction time, salt concentration, stirring speed, pH of the extraction solvent, and desorption conditions. The recoveries were in the range of 73.25-103.85 % and the relative standard deviations were lower than 6.84 %. The experiment results indicated that the present method was effective for the extraction of sulfonamides in high-fat content samples.

  14. Design and synthesis of novel 1,3-diaryltriazene-substituted sulfonamides as potent and selective carbonic anhydrase II inhibitors.

    Science.gov (United States)

    Lolak, Nabih; Akocak, Suleyman; Bua, Silvia; Koca, Murat; Supuran, Claudiu T

    2018-04-01

    A series of novel 1,3-diaryltriazene-substituted sulfonamides was synthesized by reaction of diazonium salt of 4-amino benzenesulfonamide with substituted aromatic amines. The obtained 1,3-diaryltriazene-substituted sulfonamides were investigated as inhibitors of four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms (hCA I, hCA II, hCA VII and hCA IX) are involved in various diseases such as glaucoma, epilepsy, retinitis pigmentosa, cancer, obesity, etc. All these sulfonamides were found to be potent inhibitors of the cytosolic isoform hCA II with low nanomolar to sub-nanomolar K i s in the range of 0.2-21.5 nM, as well as a moderate selectivity against other cytosolic isoforms hCA I and hCA VII, and great selectivity against membrane-bound isoform hCA IX was observed. Since hCA II is an important drug target for antiglaucoma agents and diuretics, these isoform-selective inhibitors may be considered of interest as tools for the development of new candidates for these conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Adsorption behavior and mechanism of chloramphenicols, sulfonamides, and non-antibiotic pharmaceuticals on multi-walled carbon nanotubes.

    Science.gov (United States)

    Zhao, Heng; Liu, Xue; Cao, Zhen; Zhan, Yi; Shi, Xiaodong; Yang, Yi; Zhou, Junliang; Xu, Jiang

    2016-06-05

    The adsorption behavior of different emerging contaminants (3 chloramphenicols, 7 sulfonamides, and 3 non-antibiotic pharmaceuticals) on five types of multi-walled carbon nanotubes (MWCNTs), and the underlying factors were studied. Adsorption equilibriums were reached within 12h for all compounds, and well fitted by the Freundlich isotherm model. The adsorption affinity of pharmaceuticals was positively related to the specific surface area of MWCNTs. The solution pH was an important parameter of pharmaceutical adsorption on MWCNTs, due to its impacts on the chemical speciation of pharmaceuticals and the surface electrical property of MWCNTs. The adsorption of ionizable pharmaceuticals decreased in varying degrees with the increased ionic strength. MWCNT-10 was found to be the strongest adsorbent in this study, and the Freundlich constant (KF) values were 353-2814mmol(1-n)L(n)/kg, 571-618mmol(1-n)L(n)/kg, and 317-1522mmol(1-n)L(n)/kg for sulfonamides, chloramphenicols, and non-antibiotic pharmaceuticals, respectively. The different adsorption affinity of sulfonamides might contribute to the different hydrophobic of heterocyclic substituents, while chloramphenicols adsorption was affected by the charge distribution in aromatic rings via substituent effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium(II) complexes.

    Science.gov (United States)

    Jian, Zhongbao; Falivene, Laura; Wucher, Philipp; Roesle, Philipp; Caporaso, Lucia; Cavallo, Luigi; Göttker-Schnetmann, Inigo; Mecking, Stefan

    2015-01-26

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6 H4 )2 PC6 H4 SO2 NHC6 H3 (2,6-R(1) ,R(2) )]PdMe}2 [A]2 ((X) 1(+) -A: R(1) =R(2) =H: (H) 1(+) -A; R(1) =R(2) =CH(CH3 )2 : (DIPP) 1(+) -A; R(1) =H, R(2) =CF3 : (CF3) 1(+) -A; A=BF4 or SbF6 ) and neutral palladium(II) methyl complexes {[(2-MeOC6 H4 )2 PC6 H4 SO2 NC6 H3 (2,6-R(1) ,R(2) )]PdMe(L)} ((X) 1-acetone: L=acetone; (X) 1-dmso: L=dimethyl sulfoxide; (X) 1-pyr: L=pyridine) chelated by a phosphine-sulfonamide were synthesized and fully characterized. Stoichiometric insertion of methyl acrylate (MA) into all complexes revealed that a 2,1 regiochemistry dominates in the first insertion of MA. Subsequently, for the cationic complexes (X) 1(+) -A, β-H elimination from the 2,1-insertion product (X) 2(+) -AMA-2,1 is overwhelmingly favored over a second MA insertion to yield two major products (X) 4(+) -AMA-1,2 and (X) 5(+) -AMA . By contrast, for the weakly coordinated neutral complexes (X) 1-acetone and (X) 1-dmso, a second MA insertion of the 2,1-insertion product (X) 2MA-2,1 is faster than β-H elimination and gives (X) 3MA as major products. For the strongly coordinated neutral complexes (X) 1-pyr, no second MA insertion and no β-H elimination (except for (DIPP) 2-pyrMA-2,1 ) were observed for the 2,1-insertion product (X) 2-pyrMA-2,1 . The cationic complexes (X) 1(+) -A exhibited high catalytic activities for ethylene dimerization, affording butenes (C4 ) with a high selectivity of up to 97.7 % (1-butene: 99.3 %). Differences in activities and selectivities suggest that the phosphine-sulfonamide ligands remain coordinated to the metal center in a bidentate fashion in the catalytically active species. By comparison, the neutral complexes (X) 1-acetone, (X) 1-dmso, and (X) 1-pyr showed very low activity towards ethylene to give traces of oligomers. DFT analyses taking into account the two possible coordination modes (O or N) of the sulfonamide ligand for the cationic system (CF3) 1(+) suggested

  17. Ribosome-Templated Azide-Alkyne Cycloadditions: Synthesis of Potent Macrolide Antibiotics by In Situ Click Chemistry.

    Science.gov (United States)

    Glassford, Ian; Teijaro, Christiana N; Daher, Samer S; Weil, Amy; Small, Meagan C; Redhu, Shiv K; Colussi, Dennis J; Jacobson, Marlene A; Childers, Wayne E; Buttaro, Bettina; Nicholson, Allen W; MacKerell, Alexander D; Cooperman, Barry S; Andrade, Rodrigo B

    2016-03-09

    Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered by combinatorial copper-catalyzed click chemistry, was synthesized in situ by incubating either E. coli 70S ribosomes or 50S subunits with macrolide-functionalized azide 2 and 3-ethynylaniline (3) precursors. The ribosome-templated in situ click method was expanded from a binary reaction (i.e., one azide and one alkyne) to a six-component reaction (i.e., azide 2 and five alkynes) and ultimately to a 16-component reaction (i.e., azide 2 and 15 alkynes). The extent of triazole formation correlated with ribosome affinity for the anti (1,4)-regioisomers as revealed by measured Kd values. Computational analysis using the site-identification by ligand competitive saturation (SILCS) approach indicated that the relative affinity of the ligands was associated with the alteration of macrolactone+desosamine-ribosome interactions caused by the different alkynes. Protein synthesis inhibition experiments confirmed the mechanism of action. Evaluation of the minimal inhibitory concentrations (MIC) quantified the potency of the in situ click products and demonstrated the efficacy of this method in the triaging and prioritization of potent antibiotics that target the bacterial ribosome. Cell viability assays in human fibroblasts confirmed 2 and four analogues with therapeutic indices for bactericidal activity over in vitro mammalian cytotoxicity as essentially identical to solithromycin (1).

  18. The New Macrolide-Lincosamide-Streptogramin B Resistance Gene erm(45) Is Located within a Genomic Island in Staphylococcus fleurettii

    DEFF Research Database (Denmark)

    Wipf, Juliette R K; Schwendener, Sybille; Nielsen, Jesper Boye

    2015-01-01

    Genome alignment of a macrolide, lincosamide, and streptogramin B (MLSB)-resistant Staphylococcus fleurettii strain with an MLSB-susceptible S. fleurettii strain revealed a novel 11,513-bp genomic island carrying the new erythromycin resistance methylase gene erm(45). This gene was shown to confer...... inducible MLSB resistance when cloned into Staphylococcus aureus. The erm(45)-containing island was integrated into the housekeeping gene guaA in S. fleurettii and was able to form a circular intermediate but was not transmissible to S. aureus....

  19. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Barker Peter E

    2007-05-01

    Full Text Available Abstract Background Sulfur mustard (SM is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE cells and bronchial/tracheal epithelial (BTE cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL-1β, IL-6, IL-8 and tumor necrosis factor (TNF, and expression of inducible nitric oxide synthase (iNOS were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1 fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory

  20. Cyanolide A, a glycosidic macrolide with potent Molluscicidal activity from the Papua New Guinea cyanobacterium Lyngbya bouillonii.

    Science.gov (United States)

    Pereira, Alban R; McCue, Christine F; Gerwick, William H

    2010-02-26

    Over the last 50 years, molluscicides have played a critical role in the control of schistosomiasis transmission. Cyanolide A (2), isolated from extracts of a Papua New Guinea collection of Lyngbya bouillonii, is a new and highly potent molluscicidal agent against the snail vector Biomphalaria glabrata (LC(50) = 1.2 microM). The structure of cyanolide A (2) was elucidated through extensive NMR spectroscopic analyses, yielding a symmetrical dimer that represents the newest addition to the family of glycosidic macrolides from cyanobacteria.

  1. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Science.gov (United States)

    Gao, Xiugong; Ray, Radharaman; Xiao, Yan; Barker, Peter E; Ray, Prabhati

    2007-01-01

    Background Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA) or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory cytokines and

  2. Resistance to the tetracyclines and macrolide-lincosamide-streptogramin group of antibiotics and its genetic linkage - a review.

    Science.gov (United States)

    Marosevic, Durdica; Kaevska, Marija; Jaglic, Zoran

    2017-06-12

    An excessive use of antimicrobial agents poses a risk for the selection of resistant bacteria. Of particular interest are antibiotics that have large consumption rates in both veterinary and human medicine, such as the tetracyclines and macrolide-lincosamide-streptogramin (MLS) group of antibiotics. A high load of these agents increases the risk of transmission of resistant bacteria and/or resistance determinants to humans, leading to a subsequent therapeutic failure. An increasing incidence of bacteria resistant to both tetracyclines and MLS antibiotics has been recently observed. This review summarizes the current knowledge on different tetracycline and MLS resistance genes that can be linked together on transposable elements.

  3. Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China

    Science.gov (United States)

    Shen, Yinfang; Cai, Jiehao; Davies, Mark R.; Zhang, Chi; Gao, Kun; Qiao, Dan; Jiang, Haoqin; Yao, Weilei; Li, Yuefang; Zeng, Mei; Chen, Mingliang

    2018-01-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ) non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ) non-susceptibility in Shanghai, China. GAS (n = 2,258) recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258), with the phenotype more prevalent in GAS isolated from adults (14.3%) than from children (1.2%). Eighty percent (24/30) of FQ-non-susceptible isolates were also resistant to both macrolides (ermB) and tetracycline (tetM) including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs) identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152) of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12) were macrolide and tetracycline resistant

  4. Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Yinfang Shen

    2018-03-01

    Full Text Available Streptococcus pyogenes, also known as group A Streptococcus (GAS, is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ non-susceptibility in Shanghai, China. GAS (n = 2,258 recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258, with the phenotype more prevalent in GAS isolated from adults (14.3% than from children (1.2%. Eighty percent (24/30 of FQ-non-susceptible isolates were also resistant to both macrolides (ermB and tetracycline (tetM including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152 of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12 were macrolide and tetracycline resistant

  5. UV-Vis spectroscopic study and DFT calculation on the solvent effect of trimethoprim in neat solvents and aqueous mixtures.

    Science.gov (United States)

    Almandoz, M C; Sancho, M I; Duchowicz, P R; Blanco, S E

    2014-08-14

    The solvatochromic behavior of trimethoprim (TMP) was analyzed using UV-Vis spectroscopy and DFT methods in neat and binary aqueous solvent mixtures. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima were evaluated by means of the linear solvation energy relationship concept of Kamlet and Taft. This analysis indicated that both interactions play an important role in the position of the absorption maxima in neat solvents. The simulated absorption spectra of TMP and TMP:(solvent)n complexes in ACN and H2O using TD-DFT methods were in agreement with the experimental ones. Binary aqueous mixtures containing as co-solvents DMSO, ACN and EtOH were studied. Preferential solvation was detected as a nonideal behavior of the wavenumber curve respective to the analytical mole fraction of co-solvent in all binary systems. TMP molecules were preferentially solvated by the organic solvent over the whole composition range. Index of preferential solvation, as well as the influence of solvent parameters were calculated as a function of solvent composition. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE AND FOSFOMYCIN SUSCEPTIBILITY RATES IN UNCOMPLICATED URINARY TRACT INFECTIONS: TIME TO CHANGE THE ANTIMICROBIAL PREFERENCES.

    Science.gov (United States)

    Guneysel, Ozlem; Suman, Enes; Ozturk, Tuba Cimilli

    2016-03-01

    Urinary tract infections (UTIs) are among the most common bacterial infections in adult population. They are prevalent in all age groups both in women and men. Also, UTIs are the most frequent indication for empirical antibiotic treatment in emergency department. The aim of this study was to determine the antibiotic resistance rates in the treatment of uncomplicated UTIs. Adult patients admitted to emergency department with uncomplicated UTIs were included in this cross-sectional study. Mid-stream urine samples were obtained under sterile conditions and cultured quantitatively. After 24 hours, the samples showing 10(5) colony forming unit per milliliter (CFU/mL) were tested for antibiotic susceptibility. Resistance to fosfomycin-trometamol (FT), amoxicillin-clavulanic acid (AC), ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (TMP-SMX) and cefpodoxime (CEF) was tested by Kirby-Bauer disc diffusion system. Escherichia (E.) coli accounted for the vast majority (93.4%) of the organisms isolated in the study. Among the E. coli positive patients, resistance to TMP-SMX was the most common antibiotic resistance. The E. coli species detected in our study group were least resistant to FT (2.4%). The resistance rates, especially to CEF, AC and CIP, were significantly higher in patients over 50 years of age. In conclusion, in the treatment of uncomplicated UTIs, TMP-SMX should be excluded from empirical treatment, while fosfomycin could be a viable option in all age groups.

  7. Virgin coconut oil protects against liver damage in albino rats challenged with the anti-folate combination, trimethoprim-sulfamethoxazole.

    Science.gov (United States)

    Otuechere, Chiagoziem A; Madarikan, Gbemisola; Simisola, Tinuala; Bankole, Olubukola; Osho, Adeleke

    2014-05-01

    Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad-spectrum antibiotic. However, its use is associated with toxic reactions. Virgin coconut oil (VCO), derived from coconut, has been widely used throughout history for its medicinal value. The aim of this study was to investigate the beneficial actions of VCO against TMP-SMX-induced alterations in serum biochemical end points. Twenty rats were divided into four groups. Group 1 (control) received no drug, whereas group 2 received TMP-SMX (8/40 mg/kg) twice daily for 7 days. Group 3 was administered coconut oil at a dose of 600 mg/kg body weight per day. The last group was treated with TMP-SMX (8/40 mg/kg) and coconut oil (600 mg/kg) simultaneously. Blood samples were collected from all groups on the 8th day of the experiment for measurement of serum biochemical parameters. Organ weights and coefficients were also evaluated. TMP-SMX caused a significant (p0.05) in the activities of serum aminotransferases, total acid phosphatase, γ-glutamyl transferase, uric acid, cholesterol, albumin, and urea levels. Supplementation of VCO ameliorated TMP-SMX-induced effects by restoring the levels of total bilirubin, alkaline phospahatase, and lactate dehydrogenase. The results of this study demonstrate that the active components of coconut oil had protective effects against the toxic effects induced by TMP-SMX administration, especially in the liver of rats.

  8. A comparative uncertainty study of the calibration of macrolide antibiotic reference standards using quantitative nuclear magnetic resonance and mass balance methods

    International Nuclear Information System (INIS)

    Liu Shuyu; Hu Changqin

    2007-01-01

    This study introduces the general method of quantitative nuclear magnetic resonance (qNMR) for the calibration of reference standards of macrolide antibiotics. Several qNMR experimental conditions were optimized including delay, which is an important parameter of quantification. Three kinds of macrolide antibiotics were used to validate the accuracy of the qNMR method by comparison with the results obtained by the high performance liquid chromatography (HPLC) method. The purities of five common reference standards of macrolide antibiotics were measured by the 1 H qNMR method and the mass balance method, respectively. The analysis results of the two methods were compared. The qNMR is quick and simple to use. In a new medicine research and development process, qNMR provides a new and reliable method for purity analysis of the reference standard

  9. Synthesis, spectral characterization and catalytic activity of Co(II) complexes of drugs: Crystal structure of Co(II)-trimethoprim complex

    Science.gov (United States)

    Madhupriya, Selvaraj; Elango, Kuppanagounder P.

    2014-01-01

    New Co(II) complexes with drugs such as trimethoprim (TMP), cimetidine (CTD), niacinamide (NAM) and ofloxacin (OFL) as ligands were synthesized. The complexes were characterized by analytical analysis, various spectral techniques such as FT-IR, UV-Vis, magnetic measurements and molar conductivity. The magnetic susceptibility results coupled with the electronic spectra suggested a tetrahedral geometry for the complexes. The coordination mode of trimethoprim ligand and geometry of the complex were confirmed by single crystal X-ray studies. In this complex the metal ion possesses a tetrahedral geometry with two nitrogen atom from two TMP ligands and two chloride ions coordinated to it. The catalytic activity of the complexes in aryl-aryl coupling reaction was screened and the results indicated that among the four complexes [Co(OFL)Cl(H2O)] exhibited excellent catalytic activity.

  10. The use of long acting sulfonamides, alone or with pyrimethamine, in malaria (with special reference to sulformetoxine

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    J. Herrero

    1967-06-01

    Full Text Available Review of the early literature as well as more recent results show that sulfonamides possess a distinct antimalarial activity. However, when give alone, their action is less marked and slower than that of the antimalarials commonly used in the treatment of the acute attack. Combinations with pyrimethamine provide better results, even in cases of pyrimethamine and chloroquine resistance. This warrants further investigations in an attempt to develop a therapeutic agent suitable for the treatment of such resistant cases. It may also be possible with an appropriate combination of pyrimethamine with a sulfonamide to achieve a satisfactory method for suppressive treatment both in areas with and without pyrimethamine resistance. Three main points must still be carefully studied: 1 the risk of developing malaria resistance against one or both of the components of the combination. 2 The risk of developing bacterial resistance to sulfonamides if these substances are used on a large scale in too low doses. It seems indeed that antimalarial effect with the combination of sufonamides + pyrimethamine can be obtained with doses of sulfonamides which are below those usually employed in bacterial diseases. Since the range of the ratios providing potentiation is rather large, only ratios of the combination sulfonamides: pyrimethamine should be chosen in which an antfbacterial sulfonamidemia is guaranteed. 3 It goes without sayinq that, although both pyrimethamine and modem sulfonamides, when given by themselves, have proved tc possess a large margin of safety, long term administration of their combination should be careful studied from the point of view of possible side effects. Substantial evidence has already been produced to show that the long acting sulfonamide Fanasil (Ro 4-4393 given once or once weekly possesses marked schizonticidal activity against P. falciparum. Although its action is slower than that of 4-aminoquinolines, it may be useful as a second

  11. Inducible Expression of both ermB and ermT Conferred High Macrolide Resistance in Streptococcus gallolyticus subsp. pasteurianus Isolates in China

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    Meixia Li

    2016-09-01

    Full Text Available Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010–2013. All isolates exhibited multi-drug resistance including high macrolide resistance (MIC ≥ 1024 mg/L for erythromycin, and 512 mg/L for clarithromycin. Efflux-encoding mefA and mefE genes were not detectable in these isolates. The presence of 23S rRNA mutations in specific isolates did not significantly change macrolide MICs. No nucleotide substitutions were found in genes encoding ribosomal proteins L4 or L22. The ermB and ermT genes were found in the genomes of all isolates. These two genes were acquired independently in one highly virulent isolate AL101002, and clustered with Tn916 and IS1216, respectively. The expression of both ermB and ermT in all isolates was erythromycin inducible and yielded comparable macrolide MICs in all six isolates. Taken together, inducible expression of both ermB and ermT conferred high macrolide resistance in these S. gallolyticus subsp. pasterianus isolates. Our findings reveal new macrolide resistance features in S. gallolyticus subsp. pasteurianus by both ermB and ermT.

  12. Treponema pallidum pallidum Genotypes and Macrolide Resistance Status in Syphilitic Lesions among Patients at 2 Sexually Transmitted Infection Clinics in Lima, Peru.

    Science.gov (United States)

    Flores, Juan Antonio; Vargas, Silver Keith; Leon, Segundo Ramos; Perez, Danny Giancarlo; Ramos, Lourdes Beatriz; Chow, Jeremy; Konda, Kelika Anne; Calvo, Gino Mauricio; Salvatierra, Hector J; Klausner, Jeffrey D; Caceres, Carlos Fernando

    2016-07-01

    We report the circulating genotypes and the frequency of macrolide-resistance patterns among Treponema pallidum pallidum DNA isolated from syphilitic lesions from patients who attended 2 sexual health clinics in Lima, Peru. We implemented and used a molecular typing scheme to describe local T. pallidum pallidum strains. Among 14 specimens, subtype 14d/f was the most prevalent strain in 7 fully typed T. pallidum DNA specimens obtained from men who have sex with men and transgender women presenting with chancre-like lesions. No macrolide-resistance mutations were found in T. pallidum DNA from 10 lesions.

  13. Conjugative transfer of the erm(A) gene from erythromycin-resistant Streptococcus pyogenes to macrolide-susceptible S. pyogenes, Enterococcus faecalis and Listeria innocua.

    Science.gov (United States)

    Giovanetti, E; Magi, G; Brenciani, A; Spinaci, C; Lupidi, R; Facinelli, B; Varaldo, P E

    2002-08-01

    In mating experiments, the erythromycin resistance methylase gene erm(A) was successfully transferred from erm(A)-positive clinical isolates of Streptococcus pyogenes to macrolide-susceptible recipients of S. pyogenes, Enterococcus faecalis and Listeria innocua. Compared with the SmaI macrorestriction pattern of the S. pyogenes recipient, the patterns of S. pyogenes transconjugants shared the lack of a fragment and the appearance of a new, larger fragment. This is the first experimental evidence that the erm(A) gene can be transferred from erythromycin-resistant S. pyogenes to macrolide-susceptible S. pyogenes as well as to other Gram-positive recipients.

  14. Transmission and selection of macrolide resistant Mycoplasma genitalium infections detected by rapid high resolution melt analysis.

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    Jimmy Twin

    Full Text Available BACKGROUND: Mycoplasma genitalium (MG causes urethritis, cervicitis and pelvic inflammatory disease. The MG treatment failure rate using 1 g azithromycin at an Australian Sexual Health clinic in 2007-9 was 31% (95%CI 23-40%. We developed a rapid high resolution melt analysis (HRMA assay targeting resistance mutations in the MG 23S rRNA gene, and validated it against DNA sequencing by examining pre- and post-treatment archived samples from MG-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Available MG-positive pre-treatment (n = 82 and post-treatment samples from individuals with clinical treatment failure (n = 20 were screened for 23S rRNA gene mutations. Sixteen (20% pre-treatment samples possessed resistance mutations (A2058G, A2059G, A2059C, which were significantly more common in patients with symptomatic azithromycin-treatment failure (12/26; 44% than in those clinically cured (4/56; 7%, p<0.001. All 20 patients experiencing azithromycin-failure had detectable mutations in their post-treatment samples. In 9 of these cases, the same mutational types were present in both pre- and post-treatment samples indicating transmitted resistance, whilst in 11 of these cases (55%, mutations were absent in pre-treatment samples indicating likely selection of resistant isolates have occurred. HRMA was able to detect all mutational changes determined in this study by DNA sequencing. An additional HRMA assay incorporating an unlabelled probe was also developed to detect type 4 single-nucleotide polymorphisms found in other populations, with a slightly lower sensitivity of 90%. CONCLUSIONS/SIGNIFICANCE: Treatment failure is associated with the detection of macrolide resistance mutations, which appear to be almost equally due to selection of resistant isolates following exposure to 1 g azithromycin and pre-existing transmitted resistance. The application of a rapid molecular assay to detect resistance at the time of initial detection of infection allows

  15. Mechanistic QSAR models for interpreting degradation rates of sulfonamides in UV-photocatalysis systems.

    Science.gov (United States)

    Huang, Xiangfeng; Feng, Yi; Hu, Cui; Xiao, Xiaoyu; Yu, Daliang; Zou, Xiaoming

    2015-11-01

    Photocatalysis is one of the most effective methods for treating antibiotic wastewater. Thus, it is of great significance to determine the relationship between degradation rates and structural characteristics of antibiotics in photocatalysis processes. In the present study, the photocatalytic degradation characteristics of 10 sulfonamides (SAs) were studied using two photocatalytic systems composed of nanophase titanium dioxide (nTiO2) plus ultraviolet (UV) and nTiO2/activated carbon fiber (ACF) plus UV. The results indicated that the largest apparent SA degradation rate constant (Kapp) is approximately 5 times as large as that of the smallest one. Based on the degradation mechanism and the partial least squares regression (PLS) method, optimum Quantitative Structure Activity Relationship (QSAR) models were developed for the two systems. Mechanistic models indicated that the degradation rule of SAs in the TiO2 systems strongly relates to their highest occupied molecular orbital (Ehomo), the maximum values of nucleophilic attack (f(+)x), and the minimum values of the most negative partial charge on a main-chain atom (q(C)min), whereas the maximum values of OH radical attack (f(0)x) and the apparent adsorption rate constant values (kad) are key factors affecting the degradation rule of SAs in the TiO2/ACF system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Modeling the hydrolysis of perfluorinated compounds containing carboxylic and phosphoric acid ester functions and sulfonamide groups.

    Science.gov (United States)

    Rayne, Sierra; Forest, Kaya

    2010-01-01

    Temperature-dependent rate constants were estimated for the acid- and base-catalyzed and neutral hydrolysis reactions of perfluorinated telomer acrylates (FTAcrs) and phosphate esters (FTPEs), and the S(N)1 and S(N)2 hydrolysis reactions of fluorotelomer iodides (FTIs). Under some environmental conditions, hydrolysis of monomeric FTAcrs could be rapid (half-lives of several years in marine systems and as low as several days in some landfills) and represent a dominant portion of their overall degradation. Abiotic hydrolysis of monomeric FTAcrs may be a significant contributor to current environmental loadings of fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Polymeric FTAcrs are expected to be hydrolyzed more slowly, with estimated half-lives in soil and natural waters ranging between several centuries to several millenia absent additional surface area limitations on reactivity. Poor agreement was found between the limited experimental data on FTPE hydrolysis and computational estimates, requiring more detailed experimental data before any further modeling can occur on these compounds or their perfluoroalkyl sulfonamidoethanol phosphate ester (PFSamPE) analogs. FTIs are expected to have hydrolytic half-lives of about 130 days in most natural waters, suggesting they may be contributing to substantial FTOH and PFCA inputs in aquatic systems. Perfluoroalkyl sulfonamides (PFSams) appear unlikely to undergo abiotic hydrolysis at the S-N, C-S, or N-C linkages under environmentally relevant conditions, although potentially facile S-N hydrolysis via intramolecular catalysis by ethanol and acetic acid amide substituents warrants further investigation.

  17. Synthesis of piperazine sulfonamide analogs as diabetic-II inhibitors and their molecular docking study.

    Science.gov (United States)

    Taha, Muhammad; Irshad, Maryam; Imran, Syahrul; Chigurupati, Sridevi; Selvaraj, Manikandan; Rahim, Fazal; Ismail, Nor Hadiani; Nawaz, Faisal; Khan, Khalid Mohammed

    2017-12-01

    Piperazine Sulfonamide analogs (1-19) have been synthesized, characterized by different spectroscopic techniques and evaluated for α-amylase Inhibition. Analogs 1-19 exhibited a varying degree of α-amylase inhibitory activity with IC 50 values ranging in between 1.571 ± 0.05 to 3.98 ± 0.397 μM when compared with the standard acarbose (IC 50  = 1.353 ± 0.232 μM). Compound 1, 2, 3 and 7 showed significant inhibitory effects with IC 50 value 2.348 ± 0.444, 2.064 ± 0.04, 1.571 ± 0.05 and 2.118 ± 0.204 μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Novel pyrrole derivatives bearing sulfonamide groups: Synthesis in vitro cytotoxicity evaluation, molecular docking and DFT study

    Science.gov (United States)

    Bavadi, Masoumeh; Niknam, Khodabakhsh; Shahraki, Omolbanin

    2017-10-01

    The synthesis of new derivatives of pyrrole substituted sulfonamide groups is described. The in vitro anticancer activity of these pyrroles was evaluated against MCF7, MOLT-4 and HL-60 cells using MTT assay. The target compounds showed inhibitory activity against tested cell lines. Among the compounds, compound 1a exhibited good cytotoxic activity. The potential of this analog to induce apoptosis was confirmed in a nuclear morphological assay by Hoechst 33258 staining in the PC-12 cells. Finally, molecular docking was performed to determine the probable binding mode of the designed pyrrole derivatives into the active site of FGFR1 protein. DFT calculations were carried out at the B3LYP levels of theory with 6-31+G (d,p) basis set for compound 1a. The point group (C1) of it was obtained based on the optimized structures; the calculation of the FT-IR vibrational frequencies, 1H NMR and 13C NMR chemical shifts of the compound were carried out and compared with those obtained experimentally.

  19. Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors.

    Science.gov (United States)

    Angapelly, Srinivas; Ramya, P V Sri; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Arifuddin, Mohammed; Supuran, Claudiu T

    2017-10-15

    A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (K I s in the range of 0.50-50.5nM), hCA IX (K I s of 1.8-228.5nM), and hCA XII (K I s of 3.5-96.2nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure-activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Ionic liquids for the passive sampling of sulfonamides from water-applicability and selectivity study.

    Science.gov (United States)

    Męczykowska, Hanna; Kobylis, Paulina; Stepnowski, Piotr; Caban, Magda

    2017-06-01

    Ionic liquids (ILs) are new-generation, non-volatile solvents which are designable, and their structure may be specifically adjusted to the current application needs. Therefore, it is possible to create and apply ILs which efficiently and selectively extract various analytes from different matrices. It has already been examined that ILs may be applied as receiving phases in passive sampling for the long-term water monitoring of PAHs and pharmaceuticals in water. In this paper, the concept of passive sampling with ILs (PASSIL applied as receiving phases) was continued and developed using phosphonium-, imidazolium-, and morpholinium-cation-based ILs. The target group of analytes was pharmaceuticals which represent one of the most common categories of water contaminants. Fourteen-day-long extractions using various ILs were performed in stirred conditions at a constant temperature (20 °C). The best extraction efficiency was achieved for trihexyl(tetradecyl)phosphonium dicyanamide ([P666-14][N(CN) 2 ]). For this preliminary calibration, the sampling rates were calculated for each sulfonamide. Once again, selectivity was observed in passive sampling using [P666-14][N(CN) 2 ]. Therefore, PASSIL is seen as a very promising method for pharmaceutical monitoring in water.

  1. Synthesis and anti-cancer activities of new sulfonamides 4-substituted-triazolyl nucleosides.

    Science.gov (United States)

    Alaoui, Soukaina; Dufies, Maeva; Driowya, Mohsine; Demange, Luc; Bougrin, Khalid; Robert, Guillaume; Auberger, Patrick; Pagès, Gilles; Benhida, Rachid

    2017-05-01

    Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market. To improve the activity of AICAR, we report herein an efficient synthesis of new series of sulfonamide-4-substituted-1,2,3-triazolyl nucleosides using a Cu-catalyzed 1,3-dipolar cycloaddition. All these molecules have been fully characterized and evaluated against two aggressive tumor cell lines, RCC4 and MDA-MB-231. Among them, nucleoside analogue 5i belonging to the ribose series was found to be 19 to 66-fold more active than AICAR. Western blot analyses on RCC4 cells showed that 5i displayed an interesting mode of action by inducing both apoptosis and autophagy cell death, making therefore this class of molecules highly promising for further hit-to-lead optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Synthesis of new carbon-11 labeled naphthalene-sulfonamides for PET imaging of human CCR8

    Energy Technology Data Exchange (ETDEWEB)

    Wang Min; Cooley, Benjamin; Gao, Mingzhang [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States); Miller, Kathy D.; Sledge, George W. [Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Hutchins, Gary D. [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

    2008-10-15

    Carbon-11 labeled naphthalene-sulfonamides, N-(4-(N-(4-[{sup 11}C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)benzamide ([{sup 11}C]5a), N-(4-(N-(4-[{sup 11}C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-2-methylbenzamide ([{sup 11}C]5b), N-(4-(N-(4-[{sup 11}C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-3-methylbenzamide ([{sup 11}C]5c), N-[{sup 11}C]methyl-N-methyl-4-(4-benzamidonaphthalene-1-sulfonamido) piperidine-1-carboxamide ([{sup 11}C]9a) and N-[{sup 11}C]methyl-N-methyl-4-(4-(2-methylbenzamido)naphthalene-1-sulfonamido) piperidine-1-carboxamide ([{sup 11}C]9b), have been synthesized as new potential positron emission tomography (PET) agents for imaging of human CCR8. The target tracers were prepared by either O-[{sup 11}C]methylation or N-[{sup 11}C]methylation of their corresponding precursors using [{sup 11}C]CH{sub 3}OTf and isolated by either a simplified solid-phase extraction (SPE) purification procedure or a high pressure liquid chromatography (HPLC) method in 30-50% radiochemical yields decay corrected to end of bombardment (EOB), 20-25 min overall synthesis time, and 74-111 GBq/{mu}mol specific activity at end of synthesis (EOS)

  3. Sulfonamides containing curcumin scaffold: Synthesis, characterization, carbonic anhydrase inhibition and molecular docking studies.

    Science.gov (United States)

    Ahmed, Mahmood; Qadir, Muhammad Abdul; Hameed, Abdul; Arshad, Muhammad Nadeem; Asiri, Abdullah M; Muddassar, Muhammad

    2018-02-01

    Curcumin is a multi-functional pharmacologically safe natural agent with proven cytoprotective effects to healthy human cells. In this study, a new series of sulfonamides with curcumin scaffold were synthesized, characterized and investigated for their carbonic anhydrase isoenzyme I (human) and II (bovine) isoforms. The structures of newly synthesized compounds were described by IR, 1 H NMR and 13 C NMR spectral data. Compound 14 showed the K i value of 0.99 µM with highest inhibitory activity among all other synthesized compounds against hCA-I enzyme. Similarly enzyme kinetic studies of compound 14, 16 and 30 against bCAII enzyme showed Ki values of 0.71, 0.67 and 0.71 µM respectively. Our biological assays results showed that most of active compounds have similar inhibitory activities compared to standard acetazolamide drug. The molecular docking predicted binding modes showed that these compounds bind with hCA-1 enzyme in similar fashion. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A survey of perfluoroalkyl sulfonamides in indoor and outdoor air using passive air samplers

    Energy Technology Data Exchange (ETDEWEB)

    Shoeib, M.; Harner, T. [Meteorological Service of Canada, Environment Canada (Canada); Wilford, B.; Jones, K. [Lancaster Univ. (United Kingdom). Environmental Science; Zhu, J. [Chemistry Research Division, Health Canada, Tunney' s Pasture, Ottawa (Canada)

    2004-09-15

    Perfluorooctane sulfonate (PFOS) has recently emerged as a priority environmental pollutant due to its widespread detection in biological samples from remote regions including the Arctic and the Mid-North Pacific Ocean. Because PFOS is fairly involatile, it is hypothesized that its occurrence in remote regions is the result of atmospheric transport of more volatile precursor compounds such as the perfluoroalkyl sulfonamides (PFASs). PFASs are used in variety of consumer products for water and oil resistance including surface treatments for fabric, upholstery, carpet, paper and leather. In a recent pilot study employing high volume air samples, indoor air concentrations of PFASs were approximately 100 times greater than outdoor levels. This is of significance because people typically spend about 90% of their time indoors 5 and this exposure may serve as an important uptake pathway. Indoor air also serves as a source of PFASs to the outside where PFASs are ultimately transported and distributed throughout the environment. The current study is intended to be a more comprehensive survey of indoor and outdoor air allowing more confident conclusions to be made. Passive air samplers comprised of polyurethane foam (PUF) disks were used. These are quiet, non-intrusive samplers that operate without the aid of a pump or electricity. Air movement delivers chemical to the sampler which has a high retention capacity for persistent organic pollutants (POPs). PUF disks samplers have been previously used successfully to monitor different classes of hydrophobic persistent organic pollutants POPs.

  5. Simultaneous Determination of Fluoroquinolones and Sulfonamides Originating from Sewage Sludge Compost

    Directory of Open Access Journals (Sweden)

    K. Kipper

    2017-01-01

    Full Text Available A simultaneous method for quantitative determination of traces of fluoroquinolones (FQs and sulfonamides (SAs in edible plants fertilized with sewage sludge was developed. The compounds were extracted from the plants by rapid and simple liquid extraction followed by extracts clean-up using solid phase extraction. The eluent additive 1,1,1,3,3,3-hexafluoro-2-propanol was used for liquid chromatographic detection to achieve separation of structurally similar antimicrobials like ciprofloxacin and norfloxacin. Identification and quantification of the compounds were performed using high-performance liquid chromatography with electrospray ionization mass spectrometry in selected reaction monitoring mode. Method was validated and extraction recoveries of FQs and SAs ranged from 66% to 93%. The limit of quantifications was from 5 ng/g in the case of ofloxacin to 40 ng/g for norfloxacin. The method precision ranged from 1.43% to 2.61%. The developed novel method was used to evaluate the plats antimicrobial uptake (potato (Solanum tuberosum L., carrot (Daucus carota L., lettuce (Lactuca sativa L., and wheat (Triticum vulgare L. from soil and migration of the analytes inside the plants.

  6. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

    Science.gov (United States)

    Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

    2016-04-01

    Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

  7. Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails.

    Science.gov (United States)

    Awadallah, Fadi M; Bua, Silvia; Mahmoud, Walaa R; Nada, Hossam H; Nocentini, Alessio; Supuran, Claudiu T

    2018-12-01

    Being the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC 4.2.1.1), herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N 1 -substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. The effect of the functionalisation of the sulfonamide group with five different substitution patterns, namely acetyl, pyridine, thiazole, pyrimidine, and carbamimidoyl, was evaluated in relation to the inhibition profile of the corresponding primary sulfonamide analogues. With most of these latter being nanomolar inhibitors of all four considered isoforms, a totally counterproductive effect on the inhibition potency can be ascribed to N 1 -functionalisations of the ZBG primary sulfonamide structure with pyridine, thiazole, and pyrimidine moieties. On the other hand, incorporation of less hindered groups, such as sulfonylacetamides and sulfonylguanidines, maintained a certain degree of activity dependent on the tailing moiety, with K I s spanning in the low micromolar range.

  8. Molecular ecology of macrolide-lincosamide-streptogramin B methylases in waste lagoons and subsurface waters associated with swine production.

    Science.gov (United States)

    Koike, Satoshi; Aminov, Rustam I; Yannarell, A C; Gans, Holly D; Krapac, Ivan G; Chee-Sanford, Joanne C; Mackie, Roderick I

    2010-04-01

    RNA methylase genes are common antibiotic resistance determinants for multiple drugs of the macrolide, lincosamide, and streptogramin B (MLS(B)) families. We used molecular methods to investigate the diversity, distribution, and abundance of MLS(B) methylases in waste lagoons and groundwater wells at two swine farms with a history of tylosin (a macrolide antibiotic structurally related to erythromycin) and tetracycline usage. Phylogenetic analysis guided primer design for quantification of MLS(B) resistance genes found in tylosin-producing Streptomyces (tlr(B), tlr(D)) and commensal/pathogenic bacteria (erm(A), erm(B), erm(C), erm(F), erm(G), erm(Q)). The near absence of tlr genes at these sites suggested a lack of native antibiotic-producing organisms. The gene combination erm(ABCF) was found in all lagoon samples analyzed. These four genes were also detected with high frequency in wells previously found to be contaminated by lagoon leakage. A weak correlation was found between the distribution of erm genes and previously reported patterns of tetracycline resistance determinants, suggesting that dissemination of these genes into the environment is not necessarily linked. Considerations of gene origins in history (i.e., phylogeny) and gene distributions in the landscape provide a useful "molecular ecology" framework for studying environmental spread of antibiotic resistance.

  9. Liquid chromatography-UV diode-array detection method for multi-residue determination of macrolide antibiotics in sheep's milk.

    Science.gov (United States)

    García-Mayor, M A; Garcinuño, R M; Fernández-Hernando, P; Durand-Alegría, J S

    2006-07-28

    A rapid, simple and sensitive liquid chromatography-UV diode-array detection method was developed for the simultaneous determination of seven macrolides (erythromycin, oleandomycin, roxithromycin, josamycin, spiramycin, tylosin and ivermectin) in sheep's milk. The column, mobile phase, temperature and flow rate were optimised to provide the best resolution of these analytes. The extraction of the antibiotic residues involves the treatment of protein-free samples with a combination of concentrated sodium hydroxide and ethyl acetate. Necessary defatting is achieved by alkaline hydrolysis. The recovery of each antibiotic was between 55% and 77%, with relative standard deviations ranging from 1% to 6.5%. The limit of quantification was 72.4 microg/kg for ivermectin, 48.3 microg/kg for roxithromycin, and 24.1 microg/kg for erythromycin, oleandomycin, spiramycin, josamycin and tylosin. The procedure was successfully used in the multi-residue determination of these macrolides at levels below the maximum concentrations legally allowed in milk samples.

  10. Adsorption and transformation of selected human-used macrolide antibacterial agents with iron(III) and manganese(IV) oxides

    International Nuclear Information System (INIS)

    Feitosa-Felizzola, Juliana; Hanna, Khalil; Chiron, Serge

    2009-01-01

    The adsorption/transformation of two members (clarithromycin and roxithromycin) of the macrolide (ML) antibacterial agents on the surface of three environmental subsurface sorbents (clay, iron(III) and manganese(IV) oxy-hydroxides) was investigated. The adsorption fitted well to the Freundlich model with a high sorption capacity. Adsorption probably occurred through a surface complexation mechanism and was accompanied by slow degradation of the selected MLs. Transformation proceeded through two parallel pathways: a major pathway was the hydrolysis of the cladinose sugar, and to a lesser extent the hydrolysis of the lactone ring. A minor pathway was the N-dealkylation of the amino sugar. This study indicates that Fe(III) and Mn(IV) oxy-hydroxides in aquatic sediments may play an important role in the natural attenuation of MLs. Such an attenuation route yields a range of intermediates that might retain some of their biological activity. - Iron(III) and manganese(IV) oxy-hydroxides in aquatic sediments may play an important role in the natural attenuation of macrolide antibacterial agents

  11. Adsorption and transformation of selected human-used macrolide antibacterial agents with iron(III) and manganese(IV) oxides

    Energy Technology Data Exchange (ETDEWEB)

    Feitosa-Felizzola, Juliana [Laboratoire Chimie Provence, Aix-Marseille Universites-CNRS (UMR 6264), 3 place Victor Hugo, 13331 Marseille Cedex 3 (France); Hanna, Khalil [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement, CNRS-Universite Henri Poincare-Nancy 1 (UMR 7564), 405 rue de Vandoeuvre, 54600 Villers-les-Nancy (France); Chiron, Serge [Laboratoire Chimie Provence, Aix-Marseille Universites-CNRS (UMR 6264), 3 place Victor Hugo, 13331 Marseille Cedex 3 (France)], E-mail: serge.chiron@univ-provence.fr

    2009-04-15

    The adsorption/transformation of two members (clarithromycin and roxithromycin) of the macrolide (ML) antibacterial agents on the surface of three environmental subsurface sorbents (clay, iron(III) and manganese(IV) oxy-hydroxides) was investigated. The adsorption fitted well to the Freundlich model with a high sorption capacity. Adsorption probably occurred through a surface complexation mechanism and was accompanied by slow degradation of the selected MLs. Transformation proceeded through two parallel pathways: a major pathway was the hydrolysis of the cladinose sugar, and to a lesser extent the hydrolysis of the lactone ring. A minor pathway was the N-dealkylation of the amino sugar. This study indicates that Fe(III) and Mn(IV) oxy-hydroxides in aquatic sediments may play an important role in the natural attenuation of MLs. Such an attenuation route yields a range of intermediates that might retain some of their biological activity. - Iron(III) and manganese(IV) oxy-hydroxides in aquatic sediments may play an important role in the natural attenuation of macrolide antibacterial agents.

  12. Antimicrobial Susceptibility Patterns and Macrolide Resistance Genes of β-Hemolytic Viridans Group Streptococci in a Tertiary Korean Hospital

    Science.gov (United States)

    Hwang, Gyu Yel; Jang, In Ho; Kwon, Ohgun; Kim, Hyo Youl; Yoon, Kap Jun

    2007-01-01

    The aim of this study was to investigate antimicrobial susceptibilities and macrolide resistance mechanisms of β-hemolytic viridans group streptococci (VGS) in a tertiary Korean hospital. Minimum inhibitory concentrations (MICs) of seven antimicrobials were determined for 103 β-hemolytic VGS isolated from various specimens. The macrolide resistance mechanisms of erythromycin-resistant isolates were studied by the double disk test and polymerase chain reaction (PCR). The overall resistance rates of β-hemolytic VGS were found to be 47.5% to tetracycline, 3.9% to chloramphenicol, 9.7% to erythromycin, and 6.8% to clindamycin, whereas all isolates were susceptible to penicillin G, ceftriaxone, and vancomycin. Among ten erythromycin-resistant isolates, six isolates expressed a constitutive MLSB (cMLSB) phenotype, and each of the two isolates expressed the M phenotype, and the inducible MLSB (iMLSB) phenotype. The resistance rates to erythromycin and clindamycin of β-hemolytic VGS seemed to be lower than those of non-β-hemolytic VGS in our hospital, although cMLSB phenotype carrying erm(B) was dominant in β-hemolytic VGS. PMID:17982224

  13. Macrolide resistance mechanisms and virulence factors in erythromycin-resistant Campylobacter species isolated from chicken and swine feces and carcasses.

    Science.gov (United States)

    Lim, Suk-Kyung; Moon, Dong-Chan; Chae, Myung Hwa; Kim, Hae Ji; Nam, Hyang-Mi; Kim, Su-Ran; Jang, Gum-Chan; Lee, Kichan; Jung, Suk-Chan; Lee, Hee-Soo

    2017-01-10

    Resistance to antimicrobials was measured in 73 isolates of Campylobacter jejuni (C. jejuni) and 121 isolates of Campylobacter coli (C. coli) from chicken and swine feces and carcasses in Korea. Both bacterial species showed the highest resistance to (fluoro) quinolones (ciprofloxacin and nalidixic acid) out of the nine antimicrobials tested. Erythromycin resistance was much higher in C. coli (19.0%, 23/121) than in C. jejuni (6.8%, 5/73). The mutation in the 23S rRNA gene was primarily responsible for macrolide resistance in Campylobacter isolates. Several amino acid substitutions in the L4 and L22 ribosomal proteins may play a role in the mechanism of resistance, but the role requires further evaluation. A total of eight virulence genes were detected in 28 erythromycin-resistant Campylobacter isolates. All C. jejuni isolates carried more than four such genes, while C. coli isolates carried fewer than three such genes. The high rate of resistance highlights the need to employ more prudent use of critically important antimicrobials, such as fluoroquinolones and macrolides, in swine and poultry production, and to more carefully monitor antimicrobial resistance in Campylobacter isolates in food animals.

  14. Emergence of macrolide-resistant Campylobacter strains in chicken meat in Poland and the resistance mechanisms involved.

    Science.gov (United States)

    Rożynek, Elżbieta; Maćkiw, Elżbieta; Kamińska, Wanda; Tomczuk, Katarzyna; Antos-Bielska, Małgorzata; Dzierżanowska-Fangrat, Katarzyna; Korsak, Dorota

    2013-07-01

    In this study, we investigated the molecular mechanisms involved in erythromycin resistance in the first resistant Campylobacter strains isolated from chicken meat in Poland, and analyzed their genetic relatedness. A total of 297 samples of raw chicken meat and giblets from retail trade in the Warsaw area collected between 2006 and 2009 were examined. Among 211 Campylobacter strains (52 C. jejuni and 159 C. coli), 10 C. coli isolates (4.7%) were resistant to erythromycin. All the C. jejuni strains were susceptible. Among the high-level macrolide-resistant isolates, two different point mutations within the domain V of the 23S rRNA gene were observed. Eight of the strains had adenine→guanine transitions at position 2075, two other isolates at position 2074. Sequence analysis of ribosomal proteins L4 (rplD) and L22 (rplV) indicated that ribosomal protein modifications did not contribute to macrolide resistance. A mutation in the inverted repeat in the cmeR and cmeABC intergenic region was found in a single resistant strain. The genetic relatedness of Campylobacter isolates showed that two resistant strains obtained from the same production plant in a 2-month interval were genetically identical. The risk of transmission of resistant strains via the food chain highlights the need for constant monitoring of resistance in Campylobacter isolates of human and animal hosts.

  15. Synthesis, thermodynamic properties and BSA interaction of a new Valen Shiff base derived from o-vanillin and trimethoprim

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xu; Jiang, Jian-Hong; Xiao, Sheng-Xiong [Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds and Applications, Department of Chemistry and Life Science, Xiangnan University, Chenzhou 423000, Hunan Province (China); Gu, Hui-Wen, E-mail: gruyclewee@hnu.edu.cn [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, Hunan Province (China); Li, Chuan-Hua; Ye, Li-Juan; Li, Xia; He, Du-Gui; Yao, Fei-Hong [Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds and Applications, Department of Chemistry and Life Science, Xiangnan University, Chenzhou 423000, Hunan Province (China); Li, Qiang-Guo, E-mail: liqiangguo@163.com [Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds and Applications, Department of Chemistry and Life Science, Xiangnan University, Chenzhou 423000, Hunan Province (China)

    2014-01-10

    Graphical abstract: A new single Valen Shiff base was synthesized and characterized. The thermodynamics properties of the Shiff base were investigated by microcalorimetry. In particular, the interaction between the synthetic Shiff base and BSA at four different temperatures has been investigated using fluorescence quenching method. - Highlights: • A new single Valen Shiff base was synthesized and characterized. • The thermodynamics properties of the Shiff base were investigated by microcalorimetry. • The interaction between the Shiff base and BSA has been investigated using fluorescence quenching method. - Abstract: A new Valen Shiff base (C{sub 22}H{sub 24}N{sub 4}O{sub 5}) was synthesized using equivalent moles of o-vanillin and trimethoprim. At 298.15 K, the standard molar enthalpy of formation of the new compound was estimated to be Δ{sub f}H{sub m}{sup Θ} [C{sub 22}H{sub 24}N{sub 4}O{sub 5}(s), 298.15 K] = −(696.92 ± 1.67) kJ mol{sup −1} by microcalorimetry. In particular, the interaction between the Shiff base and bovine serum albumin (BSA) has been investigated. It was proved that the fluorescence quenching of BSA by Shiff base is a result of the formation of a Shiff base-BSA complex. Quenching constants were determined using the Sterns–Volmer equation to provide a measurement of the binding site between Shiff base and BSA. The thermodynamic parameters ΔG, ΔH, and ΔS of the system at different temperatures were calculated. What is more, the distance r between donor (Trp. 213) and acceptor (Shiff base) was obtained. Finally, synchronous fluorescence spectroscopy data has suggested the association between Shiff base and BSA changed the molecular conformation of BSA.

  16. Synthesis, thermodynamic properties and BSA interaction of a new Valen Shiff base derived from o-vanillin and trimethoprim

    International Nuclear Information System (INIS)

    Li, Xu; Jiang, Jian-Hong; Xiao, Sheng-Xiong; Gu, Hui-Wen; Li, Chuan-Hua; Ye, Li-Juan; Li, Xia; He, Du-Gui; Yao, Fei-Hong; Li, Qiang-Guo

    2014-01-01

    Graphical abstract: A new single Valen Shiff base was synthesized and characterized. The thermodynamics properties of the Shiff base were investigated by microcalorimetry. In particular, the interaction between the synthetic Shiff base and BSA at four different temperatures has been investigated using fluorescence quenching method. - Highlights: • A new single Valen Shiff base was synthesized and characterized. • The thermodynamics properties of the Shiff base were investigated by microcalorimetry. • The interaction between the Shiff base and BSA has been investigated using fluorescence quenching method. - Abstract: A new Valen Shiff base (C 22 H 24 N 4 O 5 ) was synthesized using equivalent moles of o-vanillin and trimethoprim. At 298.15 K, the standard molar enthalpy of formation of the new compound was estimated to be Δ f H m Θ [C 22 H 24 N 4 O 5 (s), 298.15 K] = −(696.92 ± 1.67) kJ mol −1 by microcalorimetry. In particular, the interaction between the Shiff base and bovine serum albumin (BSA) has been investigated. It was proved that the fluorescence quenching of BSA by Shiff base is a result of the formation of a Shiff base-BSA complex. Quenching constants were determined using the Sterns–Volmer equation to provide a measurement of the binding site between Shiff base and BSA. The thermodynamic parameters ΔG, ΔH, and ΔS of the system at different temperatures were calculated. What is more, the distance r between donor (Trp. 213) and acceptor (Shiff base) was obtained. Finally, synchronous fluorescence spectroscopy data has suggested the association between Shiff base and BSA changed the molecular conformation of BSA

  17. Assessing the concentrations and risks of toxicity from the antibiotics ciprofloxacin, sulfamethoxazole, trimethoprim and erythromycin in European rivers

    International Nuclear Information System (INIS)

    Johnson, Andrew C.; Keller, Virginie; Dumont, Egon; Sumpter, John P.

    2015-01-01

    This study evaluated the potential concentrations of four antibiotics: ciprofloxacin (CIP), sulfamethoxazole (SUF), trimethoprim (TRI) and erythromycin (ERY) throughout the rivers of Europe. This involved reviewing national consumption rates together with assessing excretion and sewage treatment removal rates. From this information, it was possible to construct best, expected and worst case scenarios for the discharge of these antibiotics into rivers. Consumption data showed surprising variations, up to 200-fold in the popularity of different antibiotics across different European nations. Using the water resources model GWAVA which has a spatial resolution of approximately 6 × 9 km, river water concentrations throughout Europe were predicted based on 31-year climate data. The modelled antibiotic concentrations were within the range of measurements reported previously in European effluents and rivers. With the expected scenario, the predicted annual-average antibiotic concentrations ranged between 0 and 10 ng/L for 90% by length of surface waters. In the worst case scenario concentrations could reach between 0.1 and 1 μg/L at the most exposed locations. As both predicted and observed sewage effluent concentrations were below reported effect levels for the most sensitive aquatic wildlife, no direct toxicity in rivers is expected. Predicted river concentrations for CIP and ERY were closest to effect levels in wildlife, followed by SUF which was 2–3 orders of magnitude lower. TRI appeared to be of the least concern with around 6 orders of magnitude difference between predicted and effect levels. However, mixture toxicity may elevate this risk and antibiotic levels of 0.1–1 μg/L in hotspots may contribute to local environmental antibiotic resistance in microorganisms. - Highlights: • Antibiotic consumption varied up to 200-fold between European nations. • Antibiotic concentrations predicted to be 10 ng/L or less for most European rivers. • These antibiotic

  18. Therapeutic Response in Adult Patients with Nonsevere Chronic Paracoccidioidomycosis Treated with Sulfamethoxazole-Trimethoprim: A Retrospective Study.

    Science.gov (United States)

    Nery, Andreia F; Crepaldi, Natasha P; Rossi, Soraya B R S; Tadano, Tomoko; Leal-Santos, Fabio A; Hahn, Rosane Christine; Menezes, Valfredo M; Fontes, Cor Jesus F

    2017-08-01

    According to the Brazilian Consensus on Paracoccidioidomycosis (PCM), itraconazole is the drug of choice for treatment. However, the combination of sulfamethoxazole and trimethoprim (SMX-TMP) is most commonly used in clinical practice because of its higher availability in the public health services. The aims of this study were to evaluate the therapeutic response of patients with nonsevere chronic PCM to SMX-TMP and highlight the factors related to treatment failure. An adequate therapeutic response was defined as completely improved disease signs and symptoms after medication use for a minimum of 6 months, followed by normalized hematological and biochemical changes, radiological improvements, and negative mycological examination findings. Medical records were analyzed for 244 patients with nonsevere chronic PCM who were treated between 1998 and 2014. In total, 41.9% of the patients had PCM for ≥ 8 months. Seven (2.9%) patients were coinfected with human immunodeficiency virus (HIV). The median (25%, 75% percentiles) treatment duration was 21 (10, 25) months. Adequate treatment adherence was reported by 68.3% of patients. In addition, 73.6% of patients exhibited an adequate therapeutic response. The majority (82.6%) of patients who were treated with SMX-TMP for > 24 months displayed an adequate therapeutic response, and the frequency of adequate therapeutic response gradually decreased as the duration of treatment decreased. Treatment nonadherence ( P < 0.001) and PCM-HIV coinfection ( P = 0.019) were factors associated with therapeutic failure. The study results support the good efficacy of SMX-TMP. Attention should be given to PCM-HIV coinfection, emphasizing the concern of a higher risk of PCM therapeutic failure in these patients.

  19. Assessing the concentrations and risks of toxicity from the antibiotics ciprofloxacin, sulfamethoxazole, trimethoprim and erythromycin in European rivers

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Andrew C., E-mail: ajo@ceh.ac.uk [Centre for Ecology and Hydrology, Wallingford, Oxfordshire OX10 8BB (United Kingdom); Keller, Virginie; Dumont, Egon [Centre for Ecology and Hydrology, Wallingford, Oxfordshire OX10 8BB (United Kingdom); Sumpter, John P. [Institute for the Environment, Brunel University, Uxbridge UB8 (United Kingdom)

    2015-04-01

    This study evaluated the potential concentrations of four antibiotics: ciprofloxacin (CIP), sulfamethoxazole (SUF), trimethoprim (TRI) and erythromycin (ERY) throughout the rivers of Europe. This involved reviewing national consumption rates together with assessing excretion and sewage treatment removal rates. From this information, it was possible to construct best, expected and worst case scenarios for the discharge of these antibiotics into rivers. Consumption data showed surprising variations, up to 200-fold in the popularity of different antibiotics across different European nations. Using the water resources model GWAVA which has a spatial resolution of approximately 6 × 9 km, river water concentrations throughout Europe were predicted based on 31-year climate data. The modelled antibiotic concentrations were within the range of measurements reported previously in European effluents and rivers. With the expected scenario, the predicted annual-average antibiotic concentrations ranged between 0 and 10 ng/L for 90% by length of surface waters. In the worst case scenario concentrations could reach between 0.1 and 1 μg/L at the most exposed locations. As both predicted and observed sewage effluent concentrations were below reported effect levels for the most sensitive aquatic wildlife, no direct toxicity in rivers is expected. Predicted river concentrations for CIP and ERY were closest to effect levels in wildlife, followed by SUF which was 2–3 orders of magnitude lower. TRI appeared to be of the least concern with around 6 orders of magnitude difference between predicted and effect levels. However, mixture toxicity may elevate this risk and antibiotic levels of 0.1–1 μg/L in hotspots may contribute to local environmental antibiotic resistance in microorganisms. - Highlights: • Antibiotic consumption varied up to 200-fold between European nations. • Antibiotic concentrations predicted to be 10 ng/L or less for most European rivers. • These antibiotic

  20. Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureus in complex with the potent inhibitor trimethoprim

    Energy Technology Data Exchange (ETDEWEB)

    Heaslet, Holly; Harris, Melissa; Fahnoe, Kelly; Sarver, Ronald; Putz, Henry; Chang, Jeanne; Subramanyam, Chakrapani; Barreiro, Gabriela; Miller, J. Richard; Pfizer

    2010-09-02

    Dihydrofolate reductase (DHFR) is the enzyme responsible for the NADPH-dependent reduction of 5,6-dihydrofolate to 5,6,7,8-tetrahydrofolate, an essential cofactor in the synthesis of purines, thymidylate, methionine, and other key metabolites. Because of its importance in multiple cellular functions, DHFR has been the subject of much research targeting the enzyme with anticancer, antibacterial, and antimicrobial agents. Clinically used compounds targeting DHFR include methotrexate for the treatment of cancer and diaminopyrimidines (DAPs) such as trimethoprim (TMP) for the treatment of bacterial infections. DAP inhibitors of DHFR have been used clinically for >30 years and resistance to these agents has become widespread. Methicillin-resistant Staphylococcus aureus (MRSA), the causative agent of many serious nosocomial and community acquired infections, and other gram-positive organisms can show resistance to DAPs through mutation of the chromosomal gene or acquisition of an alternative DHFR termed 'S1 DHFR.' To develop new therapies for health threats such as MRSA, it is important to understand the molecular basis of DAP resistance. Here, we report the crystal structure of the wild-type chromosomal DHFR from S. aureus in complex with NADPH and TMP. We have also solved the structure of the exogenous, TMP resistant S1 DHFR, apo and in complex with TMP. The structural and thermodynamic data point to important molecular differences between the two enzymes that lead to dramatically reduced affinity of DAPs to S1 DHFR. These differences in enzyme binding affinity translate into reduced antibacterial activity against strains of S. aureus that express S1 DHFR.

  1. Effect of Trimethoprim-Sulfamethoxazole Prophylaxis on Antimicrobial Resistance of Fecal Escherichia coli in HIV-Infected Patients in Tanzania

    Science.gov (United States)

    Morpeth, Susan C.; Thielman, Nathan M.; Ramadhani, Habib O.; Hamilton, John D.; Ostermann, Jan; Kisenge, Peter R.; Shao, Humphrey J.; Reller, L. Barth; Itemba, Dafrosa K.; Sam, Noel E.; Bartlett, John A.; Shao, John F.; Crump, John A.

    2008-01-01

    Background Trimethoprim-sulfamethoxazole (SXT) reduces morbidity and mortality among HIV-infected persons in Africa, but its impact on antimicrobial resistance is of concern. Methods HIV-uninfected (group A), HIV-infected but not requiring SXT (group B), and HIV-infected and eligible for SXT (group C) adults were recruited into a prospective observational cohort study in Moshi, Tanzania. Stool was examined for Escherichia coli nonsusceptible to SXT at baseline and at weeks 1, 2, 4, and 24. General estimating equation models were used to assess differences in susceptibility over time and cross-resistance to other antimicrobials. Results Of 181 subjects, 118 (65.1%) were female and the median (range) age was 36 (20 to 72) years. At baseline, E. coli nonsusceptible to SXT was isolated from 23 (53.5%) of 43 patients in group A, 25 (67.6%) of 37 patients in group B, and 37 (64.9%) of 57 patients in group C. The odds ratios (P value) for SXT nonsusceptibility in group C at weeks 1, 2, 4, and 24 compared with baseline were 3.4 (0.013), 3.0 (0.019), 2.9 (0.030), and 1.5 (0.515), respectively. SXT nonsusceptibility was associated with nonsusceptibility to ampicillin, chloramphenicol, ciprofloxacin, and nalidixic acid (P ≤ 0.006). Conclusion In Tanzania, carriage of fecal E. coli nonsusceptible to SXT is common before SXT prophylaxis. Initiation of SXT leads to further loss of susceptibility to SXT and to other antimicrobials. PMID:18285712

  2. Determination of sulfonamides in serum by on-line solid-phase extraction coupled to liquid chromatography with photoinduced fluorescence detection.

    Science.gov (United States)

    Arroyo-Manzanares, Natalia; Lara, Francisco J; Airado-Rodríguez, Diego; Gámiz-Gracia, Laura; García-Campaña, Ana M

    2015-06-01

    An analytical method based on on-line solid-phase extraction coupled to liquid chromatography with photoinduced fluorescence detection has been developed to determine sulfonamides in serum. A home-made setup was used to percolate 3 mL of sample through a solid-phase extraction column. Analytes were retained onto the sorbent by an anion exchange mechanism which ensures an optimum compatibility with the subsequent chromatographic separation using a C-18 column and an on-line photoreactor in order to derivatize sulfonamides, which do not present native fluorescence. The method allowed the determination of 7 sulfonamides in serum samples previously deproteinized in less than 18 min and with limits of detection ranging between 1.8 and 3.6 mg/L. Relative recoveries between 91.5% and 102.1% were obtained with satisfactory precision since relative standard deviations were always below 10.5%. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The antibacterial activity of some sulfonamides and sulfonyl hydrazones, and 2D-QSAR study of a series of sulfonyl hydrazones

    Science.gov (United States)

    Aslan, H. Güzin; Özcan, Servet; Karacan, Nurcan

    2012-12-01

    Benzenesulfonicacid-1-methylhydrazide (1) and its four aromatic sulfonyl hydrazone derivatives (1a-1d), N-(3-amino-2-hydroxypropyl)benzene sulfonamide (2) and N-(2-hydroxyethyl)benzenesulfonamide (3) were synthesized and their structures were determined by IR, 1H NMR, 13C NMR, and LCMS techniques. Antibacterial activities of new synthesized compounds were evaluated against various bacteria strains by microdilution and disk diffusion methods. The experimental results show that presence of OH group on sulfonamides reduces the antimicrobial activity, and antimicrobial activities of the sulfonyl hydrazones (1a-1d) are smaller than that of the parent sulfonamide (1), except Candida albicans. In addition, 2D-QSAR analysis was performed on 28 aromatic sulfonyl hydrazones as antimicrobial agents against Escherichia coli and Staphylococcus aureus. In the QSAR models, the most important descriptor is total point-charge component of the molecular dipole for E. coli, and partial negative surface area (PNSA-1) for S. aureus.

  4. Synthesis and carbonic anhydrase I, II, VII, and IX inhibition studies with a series of benzo[d]thiazole-5- and 6-sulfonamides.

    Science.gov (United States)

    Abdoli, Morteza; Angeli, Andrea; Bozdag, Murat; Carta, Fabrizio; Kakanejadifard, Ali; Saeidian, Hamid; Supuran, Claudiu T

    2017-12-01

    A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino-substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the heterocyclic ring) compounds led to several interesting inhibitors against the cytosolic hCA I, II and VII, as well as the transmembrane, tumor-associated hCA IX isoforms. Several subnanomolar/low nanomolar, isoform-selective sulfonamide inhibitors targeting hCA II, VII and IX were detected. The sharp structure-activity relationship for CA inhibition with this small series of derivatives, with important changes of activity observed even after minor changes in the scaffold or at the 2-amino moiety, make this class of scarcely investigated sulfonamides of particular interest for further investigations.

  5. In situ derivatization and hollow-fiber liquid-phase microextraction to determine sulfonamides in water using UHPLC with fluorescence detection.

    Science.gov (United States)

    Yang, Lihua; Shi, Yang; Li, Jinjin; Luan, Tiangang

    2017-12-30

    A sensitive method for determining sulfonamides in water was developed and validated through in situ derivatization and hollow-fiber liquid-phase microextraction with ultra-high performance liquid chromatography and fluorescence detection. The target sulfonamides were sulfadiazine, sulfacetamide, sulfamerazine, sulfamethazine, sulfamethoxypyridazine, sulfachloropyridazine, sulfamethoxazole, and sulfisoxazole. Following in situ derivatization with fluorescamine, three-phase hollow-fiber liquid-phase microextraction with an S 6/2 polypropylene hollow-fiber membrane was applied automatically using a multipurpose autosampler. Experimental parameters including derivatization time, choice of organic phase, pH of donor and acceptor phase, stirring rate, extraction temperature and time were optimized. Under optimized conditions, the target sulfonamides achieved excellent linearity with correlation coefficients of 0.9924-0.9994 within the concentration range of 0.05-5 μg/L. The limits of detection of the eight sulfonamides were 3.1-11.2 ng/L, and the limits of quantification were 10.3-37.3 ng/L. Enrichment factors of 0.1 and 5 μg/L sulfonamides spiked in lake water were 14-60, and recoveries were 56-113% with relative standard derivations of 3-19%. Applied with the developed method, sulfamerazine and sulfamethoxazole were measurable in both influent and effluent water of the three sewage treatment plants in Guangzhou, China. The developed method was sensitive and provided an alternative method for simultaneously enriching and quantifying multiple sulfonamides in environmental water. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. [Synthesis and structure of silver(I) coordination polymers with bis(pyridyl) ligands linked by an aromatic sulfonamide].

    Science.gov (United States)

    Katagiri, Kosuke

    2014-01-01

    Aromatic sulfonamides exist in a synclinal conformation with the twisted structure arising from rotation around the S-N bond in both the solid state and in solution. Simple bidentate ligands containing the sulfonamide moiety can be extended to form elongated ligands, and optically active components can be added to form a versatile building block for the construction of coordination polymers with many structures. Mixing the simple ligands 1 and 2 and the elongated ligands 3 and 4 with different Ag(I) salts yielded the corresponding complexes [Ag(1)OTf]n (1a), [Ag(2)]n•nOTf(2a), [Ag(3)OTf]n (3a), [Ag(3)]n•nBF₄ (3b), [Ag(4)CH₃CN]n•nBF₄•nCHCl₃ (4b), and [Ag(4)]n•nSbF₆•nCH₄O (4c). Straight chains and racemic helical polymers were observed in the crystal structure of complexes 1a and 2a, respectively. In the crystal structures of complexes 3a and 4b, infinite 1D straight chains containing a T-shaped coordination geometry about the Ag(I) centers were formed by the reaction of ligands 3 or 4 with Ag(I) salts in CH₃CN/CHCl₃. A continuous 1D coordination polymer containing a racemic mixture of left- and right-handed helices formed in the crystal structure of complex 3b. Furthermore, a layered coordination polymer consisting of a racemic mixture of left- and right-handed polymers was observed from the crystal structure of complex 4c. The construction of optically pure left- or right-handed 1D helical polymers via the introduction of chiral functional groups on the nitrogen atom of the sulfonamide ligand is currently under investigation in our laboratory.

  7. Continuous degradation of a mixture of sulfonamides by Trametes versicolor and identification of metabolites from sulfapyridine and sulfathiazole

    International Nuclear Information System (INIS)

    Rodríguez-Rodríguez, Carlos E.; Jesús García-Galán, Ma.; Blánquez, Paqui; Díaz-Cruz, M. Silvia; Barceló, Damià; Caminal, Glòria; Vicent, Teresa

    2012-01-01

    Highlights: ► Degradation of sulfapyridine and sulfathiazole by Trametes versicolor was evaluated. ► The role of laccase and cytochrome P450 was determined. ► Degradation metabolites were identified for sulfapyridine (8) and sulfathiazole (5). ► A mixture of three sulfonamides was degraded in a continuous fluidized bed reactor. - Abstract: In this study, we assessed the degradation of the sulfonamides sulfapyridine (SPY) and sulfathiazole (STZ) by the white-rot fungus Trametes versicolor. Complete degradation was accomplished in fungal cultures at initial pollutant concentrations of approximately 10 mg L −1 , although a longer period of time was needed to completely remove STZ in comparison to SPY. When cytochrome P450 inhibitors were added to the fungal cultures, STZ degradation was partially suppressed, while no additional effect was observed for SPY. Experiments with purified laccase and laccase mediators caused the removal of greater than 75% of each antibiotic. Ultra-performance liquid chromatography-quadupole time of flight mass spectrometry (UPLC-QqTOF-MS) analyses allowed the identification of a total of eight degradation intermediates of SPY in both the in vivo and the laccase experiments, being its desulfonated moiety the commonly detected product. For STZ, a total of five products were identified. A fluidized bed reactor with T. versicolor pellets degraded a mixture of sulfonamides (SPY, STZ and sulfamethazine, SMZ) by greater than 94% each at a hydraulic residence time of 72 h. Because wastewater contains many diverse pollutants, these results highlight the potential of T. versicolor as a bioremediation agent not only for the removal of antibiotics but also for the elimination of a wide range of contaminants.

  8. Sulfonamide-resistant bacteria and their resistance genes in soils fertilized with manures from Jiangsu Province, Southeastern China.

    Directory of Open Access Journals (Sweden)

    Na Wang

    Full Text Available Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of antibiotic resistance genes (ARGs increasingly in the soil. The frequency of sulfonamide resistance genes was sul1 > sul2 > sul3 in pig-manured soil DNA and sul2 > sul1 > sul3 in chicken-manured soil DNA. Further analysis suggested that the frequency distribution of the sul genes in the genomic DNA and plasmids of the SR isolates from manured soil was sul2 > sul1 > sul3 overall (p<0.05. The combination of sul1 and sul2 was the most frequent, and the co-existence of sul1 and sul3 was not found either in the genomic DNA or plasmids. The sample type, animal type and sampling time can influence the prevalence and distribution pattern of sulfonamide resistance genes. The present study also indicated that Bacillus, Pseudomonas and Shigella were the most prevalent sul-positive genera in the soil, suggesting a potential human health risk. The above results could be important in the evaluation of antibiotic-resistant bacteria and genes from manure as sources of agricultural soil pollution; the results also demonstrate the necessity and urgency of the regulation and supervision of veterinary antibiotics in China.

  9. Determination of sulfonamides in animal tissues by modified QuEChERS and liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Wen, Ching-Hsuan; Lin, Shu-Ling; Fuh, Ming-Ren

    2017-03-01

    In this study, the salting-out solvent extraction and dispersive solid-phase extraction (dSPE) clean-up steps in QuEChERS (quick, easy, cheap, effective, rugged, and safe) method were optimized to reduce matrix effect and efficiently extract target sulfonamides from a variety of edible animal tissues. The extracted sulfonamides were then analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Good extraction recoveries (74.0-100.3% in five different sources of animal tissues; n=3) with acceptable matrix effect (<10%, except for liver samples) were obtained using the proposed method. For the first time, a commercial ND-lipids cartridge was used to remove hydrophobic matrix components from fat-rich animal tissues in the clean-up step of QuEChERS. In addition, good linearity (0.125-12.5ngg -1 ) was observed using matrix-matched calibration (in beef). Limits of detection (LODs) were estimated at 0.01-0.03ngg -1 in beef, pork, and chicken samples. For beef tripe and pig liver samples, the LODs were in the range of 0.02-0.04ngg -1 . Good intra-day/inter-day precision (1.0-10.5%/0.4-8.0%) and accuracy (95.2-107.2%/97.8-102.1%) were also achieved using the modified QuEChERS for sample pretreatment. The applicability of the modified QuEChERS-LC-MS/MS method was demonstrated by determining the occurrence of target sulfonamides in various edible animal tissues for potential food safety analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Continuous degradation of a mixture of sulfonamides by Trametes versicolor and identification of metabolites from sulfapyridine and sulfathiazole

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Rodriguez, Carlos E., E-mail: CarlosEsteban.Rodriguez@uab.cat [Unitat asociada de Biocatalisi Aplicada IQAC-CSIC, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Centro de Investigacion en Contaminacion Ambiental, Universidad de Costa Rica, 2060 San Jose (Costa Rica); Jesus Garcia-Galan, Ma. [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Blanquez, Paqui [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Diaz-Cruz, M. Silvia [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Barcelo, Damia [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Catalan Institute for Water Research (ICRA), Parc Cientific i Tecnologic de la Universitat de Girona, C/Emili Grahit, 101 Edifici H2O, E-17003 Girona (Spain); Caminal, Gloria [Unitat asociada de Biocatalisi Aplicada IQAC-CSIC, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Vicent, Teresa [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain)

    2012-04-30

    Highlights: Black-Right-Pointing-Pointer Degradation of sulfapyridine and sulfathiazole by Trametes versicolor was evaluated. Black-Right-Pointing-Pointer The role of laccase and cytochrome P450 was determined. Black-Right-Pointing-Pointer Degradation metabolites were identified for sulfapyridine (8) and sulfathiazole (5). Black-Right-Pointing-Pointer A mixture of three sulfonamides was degraded in a continuous fluidized bed reactor. - Abstract: In this study, we assessed the degradation of the sulfonamides sulfapyridine (SPY) and sulfathiazole (STZ) by the white-rot fungus Trametes versicolor. Complete degradation was accomplished in fungal cultures at initial pollutant concentrations of approximately 10 mg L{sup -1}, although a longer period of time was needed to completely remove STZ in comparison to SPY. When cytochrome P450 inhibitors were added to the fungal cultures, STZ degradation was partially suppressed, while no additional effect was observed for SPY. Experiments with purified laccase and laccase mediators caused the removal of greater than 75% of each antibiotic. Ultra-performance liquid chromatography-quadupole time of flight mass spectrometry (UPLC-QqTOF-MS) analyses allowed the identification of a total of eight degradation intermediates of SPY in both the in vivo and the laccase experiments, being its desulfonated moiety the commonly detected product. For STZ, a total of five products were identified. A fluidized bed reactor with T. versicolor pellets degraded a mixture of sulfonamides (SPY, STZ and sulfamethazine, SMZ) by greater than 94% each at a hydraulic residence time of 72 h. Because wastewater contains many diverse pollutants, these results highlight the potential of T. versicolor as a bioremediation agent not only for the removal of antibiotics but also for the elimination of a wide range of contaminants.

  11. Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy

    Science.gov (United States)

    Liu, Mingfu; Douthwaite, Stephen

    2002-01-01

    The macrolide antibiotic tylosin has been used extensively in veterinary medicine and exerts potent antimicrobial activity against Gram-positive bacteria. Tylosin-synthesizing strains of the Gram-positive bacterium Streptomyces fradiae protect themselves from their own product by differential expression of four resistance determinants, tlrA, tlrB, tlrC, and tlrD. The tlrB and tlrD genes encode methyltransferases that add single methyl groups at 23S rRNA nucleotides G748 and A2058, respectively. Here we show that methylation by neither TlrB nor TlrD is sufficient on its own to give tylosin resistance, and resistance is conferred by the G748 and A2058 methylations acting together in synergy. This synergistic mechanism of resistance is specific for the macrolides tylosin and mycinamycin that possess sugars extending from the 5- and 14-positions of the macrolactone ring and is not observed for macrolides, such as carbomycin, spiramycin, and erythromycin, that have different constellations of sugars. The manner in which the G748 and A2058 methylations coincide with the glycosylation patterns of tylosin and mycinamycin reflects unambiguously how these macrolides fit into their binding site within the bacterial 50S ribosomal subunit. PMID:12417742

  12. In vitro complex formation and inhibition of hepatic cytochrome P450 activity by different macrolides and tiamulin in goats and cattle

    NARCIS (Netherlands)

    Zweers-Zeilmaker, W.M.; Miert, A.S.J.P.A.M. van; Horbach, G.J.; Witkamp, R.F.

    1998-01-01

    In humans, clinically relevant drug–drug interactions occur with some macrolide antibiotics via the formation of stable metabolic intermediate (MI) complexes with enzymes of the cytochrome P4503A (CYP3A) subfamily. The formation of such complexes can result in a decreased biotransformation rate of

  13. Synthesis of some new heterocyclic compounds bearing a sulfonamide moiety and studying their combined anticancer effect with γ-radiation

    International Nuclear Information System (INIS)

    El-Hossary, E.M.M.

    2010-01-01

    In search for new cytotoxic agents with improved anticancer profile, some new halogen-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a free sulfonamide moiety were synthesized. All the newly synthesized target compounds were subjected to in vitro anticancer screening against human breast cancer cell line (MCF7). The most potent compounds, as concluded from the in vitro anticancer screening, were selected to be evaluated again for their in vitro anticancer activity in combination with radiation. Also, the newly synthesized compounds were docked in the active site of the carbonic anhydrase enzyme

  14. Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques.

    Science.gov (United States)

    Naeeminejad, Samane; Assaran Darban, Reza; Beigoli, Sima; Saberi, Mohammad Reza; Chamani, Jamshidkhan

    2017-11-01

    The interaction between synthesized heterocyclic benzene sulfonamide compounds, N-(7-benzyl-56-biphenyl-2m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-benzene sulfonamide (HBS 1 ), N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d] pyrimidine-4-yl)-4-methyl- benzene sulfonamide (HBS 2 ), and N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-4-chloro-benzene sulfonamide (HBS 3 ) with Hb was studied by fluorescence quenching, zeta potentional, circular dichroism, and molecular modeling techniques. The fluorescence spectroscopy experiments were performed in order to study the conformational changes, possibly due to a discrete reorganization of Trp residues during binding between HBS derivatives and Hb. The variation of the K SV value suggested that hydrophobic and electrostatic interactions were the predominant intermolecular forces stabilizing the complex. The K SV1 ans K SV2 values of HBS derivatives with Hb are .6 × 10 13 and 3 × 10 13  M -1 for Hb-HBS 1 , 1 × 10 13 and 4 × 10 13  M -1 for Hb-HBS 2 , .9 × 10 13 , and 6 × 10 13  M -1 for Hb-HBS 3 , respectively. The molecular distances between Hb and HBS derivatives in binary and ternary systems were estimated according to Förster's theory of dipole-dipole non-radiation energy transfer. The quantitative analysis data of circular dichroism spectra demonstrated that the binding of the three HBS derivatives to Hb induced conformational changes in Hb. Changes in the zeta potential of the Hb-HBS derivatives complexes demonstrated a hydrophobic adsorption of the anionic ligand onto the surface of Hb as well as both electrostatic and hydrophobic adsorption in the case of the complex. The modeling data thus confirmed the experimental results. This study is expected to provide important insight into the interaction of Hb with three HBS derivatives to use in various toxicological and therapeutic processes.

  15. Pd(II)-catalyzed ortho-hydroxylation and intramolecular oxidative C-C coupling of N- benzylbenzene sulfonamides

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Eun Joo; Jo, Yoon Hyung; Jang, Min Jung; Youn, So Won [Dept. of Chemistry and Research Institute for Natural Sciences, Center for New Directions in Organic Synthesis, Hanyang University, Seoul (Korea, Republic of)

    2015-02-15

    We reported highly effective Pd-catalyzed C-C and/or C-N bond formations via C-H activation of aniline derivatives. Considering the lack of regioselective C(sp{sup 2}) H hydroxylation of benzylamines, our continued interest in Pd-catalyzed C-H bond functionalization prompted us to investigate the possibility of a Pd-catalyzed ortho-hydroxylation of NH-containing benzylamines. We have developed the Pd-catalyzed ortho-hydroxylation and/or intramolecular oxidative C-C coupling of N-benzyl sulfonamides, which operate through two different postulated mechanistic routes, as depicted in Scheme 2, depending on the reaction conditions.

  16. AlCl3catalyzed coupling of N-benzylic sulfonamides with 2-substituted cyanoacetates through carbon-nitrogen bond cleavage.

    Science.gov (United States)

    Hu, Chen; Hong, Gang; Qian, Xiaofei; Kim, Kwang Rim; Zhu, Xiaoyan; Wang, Limin

    2017-06-14

    A new cross-coupling reaction of N-benzylic sulfonamides with 2-substituted cyanoacetates for the synthesis of 2-substituted benzylbenzene was reported. In the presence of AlCl 3 , a broad range of N-benzylic sulfonamides reacted smoothly with 2-substituted cyanoacetates to afford structurally diverse benzylbenzenes in moderate to excellent yields. The conversion could be enlarged to gram-scale efficiently. The practicability of this approach was further manifested in the synthesis of a related bioactive agent with high anti-inflammatory activity.

  17. The origin of enantioselectivity in the l-threonine-derived phosphine-sulfonamide catalyzed aza-Morita-Baylis-Hillman reaction: Effects of the intramolecular hydrogen bonding

    KAUST Repository

    Lee, Richmond

    2013-01-01

    l-Threonine-derived phosphine-sulfonamide 4 was identified as the most efficient catalyst to promote enantioselective aza-Morita-Baylis-Hillman (MBH) reactions, affording the desired aza-MBH adducts with excellent enantioselectivities. Density functional theory (DFT) studies were carried out to elucidate the origin of the observed enantioselectivity. The importance of the intramolecular N-H⋯O hydrogen-bonding interaction between the sulfonamide and enolate groups was identified to be crucial in inducing a high degree of stereochemical control in both the enolate addition to imine and the subsequent proton transfer step, affording aza-MBH reactions with excellent enantioselectivity. © 2013 The Royal Society of Chemistry.

  18. Distribution of Genes Encoding Resistance to Macrolides Among Staphylococci Isolated From the Nasal Cavity of Hospital Employees in Khorramabad, Iran.

    Science.gov (United States)

    Goudarzi, Gholamreza; Tahmasbi, Farzad; Anbari, Khatereh; Ghafarzadeh, Masoumeh

    2016-02-01

    Epidemiological data on antibiotic susceptibility of Staphylococcus strains isolated from nasal carriers in each region can be helpful to select appropriate drugs to eradicate carriage states, control nosocomial infections and also treat patients. The current study aimed to investigate the antibiotic resistance profile and the molecular prevalence of the ermA, ermB, ermC and msrA genes among Staphylococcus strains isolated from the anterior nares of hospital employees. In this cross-sectional study, a total of 100 Staphylococcus isolates, 51 Staphylococcus aureus, 49 coagulase-negative staphylococci (CoNS) were isolated from the anterior nares of hospital employees in Khorramabad, Iran. Susceptibility pattern to macrolide antibiotics were determined using the disk diffusion method. The polymerase chain reaction (PCR) assay was applied to determine the major erythromycin-resistant genes (ermA, ermB, ermC and msrA). Fifty-three (53%) isolates were simultaneously resistant to erythromycin, azithromycin and clarithromycin (cross-resistance); while 8 (8%) isolates had variable macrolide susceptibility pattern. Among the S. aureus isolates, the difference in prevalence of resistance to erythromycin between males and females was significant (P = 0.011). The frequency of ermA, ermB, ermC, and msrA genes were 3%, 5%, 33% and 20%, respectively. It was also found that out of 53 isolates resistant to erythromycin, 44 (83%) isolates (eight S. aureus and thirty-six CoNS strains) carried at least one of the four tested genes. Eight (8%) isolates had intermediate phenotype to erythromycin, in which 4 (50%) isolates carried ermB or ermC genes. In addition, out of 39 erythromycin-susceptible isolates, 3 (7.7%) isolates were positive for ermB or ermC genes. No entire association was found between genotype and phenotype methods to detect macrolides-resistant isolates. In addition, distribution of genetically erythromycin-resistant isolates is geographically different among

  19. Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin.

    Science.gov (United States)

    Guschin, Alexander; Ryzhikh, Pavel; Rumyantseva, Tatiana; Gomberg, Mikhail; Unemo, Magnus

    2015-02-03

    Azithromycin has been widely used for Mycoplasma genitalium treatment internationally. However, the eradication efficacy has substantially declined recent decade. In Russia, josamycin (another macrolide) is the recommended first-line treatment for M. genitalium infections, however, no data regarding treatment efficacy with josamycin and resistance in M. genitalium infections have been internationally published. We examined the M. genitalium prevalence in males attending an STI clinic in Moscow, Russia from December 2006 to January 2008, investigated treatment efficacy with josamycin in male urethritis, and monitored the M. genitalium DNA eradication dynamics and selection of macrolide resistance in M. genitalium during this treatment. Microscopy and real-time PCRs were used to diagnose urethritis and non-viral STIs, respectively, in males (n = 320). M. genitalium positive patients were treated with recommended josamycin regimen and treatment efficacy was monitored using quantitative real-time PCR. Macrolide resistance mutations were identified using sequencing of the 23S rRNA gene. Forty-seven (14.7%) males were positive for M. genitalium only and most (85.1%) of these had symptoms and signs of urethritis. Forty-six (97.9%) males agreed to participate in the treatment efficacy monitoring. All the pre-treatment M. genitalium specimens had wild-type 23S rRNA. The elimination of M. genitalium DNA was substantially faster in patients with lower pre-treatment M. genitalium load, and the total eradication rate was 43/46 (93.5%). Of the six patients with high pre-treatment M. genitalium load, three (50%) remained positive post-treatment and these positive specimens contained macrolide resistance mutations in the 23S rRNA gene, i.e., A2059G (n = 2) and A2062G (n = 1). M. genitalium was a frequent cause of male urethritis in Moscow, Russia. The pre-treatment M. genitalium load might be an effective predictor of eradication efficacy with macrolides (and possibly

  20. Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Adrian Ceccato

    Full Text Available Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial.We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone and corticosteroid arm (placebo or corticosteroids. The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure.The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374; however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31% vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24% vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0% vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009. We found