nitrofuran
204833280
An update on derivatisation and repurposing of clinical nitrofuran drugs.
5 nitrofurans (NFs) have been in clinical use for over 60 years. These affordable drugs are used for the treatment of a broad spectrum of diseases ranging from urinary tract infections to cancer. The anti pathogenic effect of clinical NFs occurs following a step wise process involving activation by azoreduction, followed by nitroreduction catalysed by azoreductases and nitroreductases (NTRs) respectively. Azoreduction yields stable metabolites that have the ability to covalently bind to cellular proteins. Nitroreduction, on the other hand, occurs by type I or II reduction of the nitro group in the presence of parasitic NADPH cytochrome P450 reductases. Type I NTRs catalyse, under anaerobic conditions, the reduction of NFs to produce anti pathogenic hydroxylamine. Under aerobic conditions, nitroreduction catalysed by type II NTRs produces reactive oxygen and nitrogen species (ROS/RNS) causing oxidative stress to pathogens and ultimate death. This multi activity nature of NFs thus allows the repurposing of these drugs from agricultural chemicals and basic antibiotics to efficient therapies against human life threatening diseases. Cases of NF resistance in pathogens are also limited likely due to this multi activity, as well as effectivity under both aerobic and anaerobic conditions. However, multi activity of these drugs can also infer toxicity. Molecular derivatisation is an effective strategy to improve efficacy, lower toxicity, diversify activity and address pathogen resistance associated with the use of these drugs.
European journal of pharmaceutical sciences official journal of the European Federation for Pharmaceutical Sciences
Nonkululeko H Zuma Janine Aucamp David D N'Da
208751802
Preparation and application of nitrofuran sensor in aquaculture water
ABSTRACT The abuse of nitrofuran in aquaculture will lead to serious environmental pollution. In this study, a sensor of poly(acid chrome blue K) modified glassy carbon electrode was prepared by cyclic voltammetry. Nitrofurazone (NF) was used as the model for studying the electrochemical behaviour of nitrofuran on the modified electrode. The NF showed adsorption controlled characteristics on the modified electrode. After enrichment for 100 s at 0.0 V, the reduction peak of NF was quantitatively analysed by differential pulse voltammetry. The reduction peak current at the prepared sensor was 10.42 times that of the bare glassy carbon electrode. The reduction peak current of NF was proportional to the concentration within the ranges of 0.2 15.0 and 15.0 80.0 mM, and the limit of detection was 0.028 mM. Under optimised conditions, nitrofuran antibiotics, such as furazolidone and nitrofurantoin, were measured. The linear ranges of furazolidone and nitrofurantoin were 10.0 60.0 and 5.0 30.0 mM, respectively, with corresponding detection limits of 0.19 and 0.072 mM. The modified electrode was simple to prepare and showed good sensitivity and reproducibility. The modified electrode was used for detecting NF in cultured water samples, and the recovery was 92.1% 110.6% Thus, it shows promising application potential in the detection of actual samples.
International Journal of Environmental Analytical Chemistry
Chunxiang Chen Wen Chen Jinlong Jiang Lei Qian Feng Qiu
201831557
Novel 5 Nitrofuran Activating Reductase in Escherichia coli
The global spread of multidrug resistant enterobacteria warrants new strategies to combat these pathogens. One possible approach is the reconsideration of "old" antimicrobials, which remain effective after decades of use. Synthetic 5 nitrofurans such as furazolidone, nitrofurantoin, and nitrofurazone are such a class of antimicrobial drugs. ABSTRACT The global spread of multidrug resistant enterobacteria warrants new strategies to combat these pathogens. One possible approach is the reconsideration of "old" antimicrobials, which remain effective after decades of use. Synthetic 5 nitrofurans such as furazolidone, nitrofurantoin, and nitrofurazone are such a class of antimicrobial drugs. Recent epidemiological data showed a very low prevalence of resistance to this antimicrobial class among clinical Escherichia coli isolates in various parts of the world, forecasting the increasing importance of its uses to battle antibiotic resistant enterobacteria. However, although they have had a long history of clinical use, a detailed understanding of the 5 nitrofurans' mechanisms of action remains limited. Nitrofurans are known as prodrugs that are activated in E. coli by reduction catalyzed by two redundant nitroreductases, NfsA and NfsB. Furazolidone, nevertheless, retains relatively significant antibacterial activity in the nitroreductase deficient DnfsA DnfsB E. coli strain, indicating the presence of additional activating enzymes and/or antibacterial activity of the unreduced form. Using genome sequencing, genetic, biochemical, and bioinformatic approaches, we discovered a novel 5 nitrofuran activating enzyme, AhpF, in E. coli. The discovery of a new nitrofuran reducing enzyme opens new avenues for overcoming 5 nitrofuran resistance, such as designing nitrofuran analogues with higher affinity for AhpF or screening for adjuvants that enhance AhpF expression.
Antimicrobial Agents and Chemotherapy
Vuong Van Hung Le Ieuan G Davies Christina D Moon Dave Wheeler Patrick J Biggs Jasna Rakonjac
21334660
Accurate Quantitation and Analysis of Nitrofuran Metabolites, Chloramphenicol, and Florfenicol in Seafood by Ultrahigh Performance Liquid Chromatography Tandem Mass Spectrometry: Method Validation and Regulatory Samples.
We developed and validated a method for the extraction, identification, and quantitation of four nitrofuran metabolites, 3 amino 2 oxazolidinone (AOZ) 3 amino 5 morpholinomethyl 2 oxazolidinone (AMOZ) semicarbazide (SC) and 1 aminohydantoin (AHD) as well as chloramphenicol and florfenicol in a variety of seafood commodities. Samples were extracted by liquid liquid extraction techniques, analyzed by ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC MS/MS) and quantitated using commercially sourced, derivatized nitrofuran metabolites, with their isotopically labeled internal standards in solvent. We obtained recoveries of 90 100% at various fortification levels. The limit of detection (LOD) was set at 0.25 ng/g for AMOZ and AOZ, 1 ng/g for AHD and SC, and 0.1 ng/g for the phenicols. Various extraction methods, standard stability, derivatization efficiency, and improvements to conventional quantitation techniques were also investigated. We successfully applied this method to the identification and quantitation of nitrofuran metabolites and phenicols in 102 imported seafood products. Our results revealed that four of the samples contained residues from banned veterinary drugs.
Journal of agricultural and food chemistry
Fadi Aldeek Kevin C Hsieh Obiadada N Ugochukwu Ghislain Gerard Walter Hammack
207250173
Investigating the structure activity relationships of N' (5 nitrofuran 2 yl) methylene] substituted hydrazides against Trypanosoma cruzi to design novel active compounds.
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected chronic tropical infection endemic in Latin America. New and effective treatments are urgently needed because the two available drugs benznidazole (BZD) and nifurtimox (NFX) have limited curative power in the chronic phase of the disease. We have previously reported the design and synthesis of N' (5 nitrofuran 2 yl) methylene] substituted hydrazides that showed high trypanocidal activity against axenic epimastigote forms of three T. cruzi strains. Here we show that these compounds are also active against a BZD and NFX resistant strain. Herein, multivariate approaches (hierarchical cluster analysis and principal component analysis) were applied to a set of thirty six formerly characterized compounds. Based on the findings from exploratory data analysis, novel compounds were designed and synthesized. These compounds showed two to three fold higher trypanocidal activity against epimastigote forms than the previous set and were 25 30 fold more active than BZD. Their activity was also evaluated against intracellular amastigotes by high content screening (HCS) The most active compounds (BSF 38 to BSF 40) showed a selective index (SI' greater than 200, in contrast to the SI' values of reference drugs (NFX, 16.45; BZD, 3) and a 70 fold greater activity than BZD. These findings indicate that nitrofuran compounds designed based on the activity against epimastigote forms show promising trypanocidal activity against intracellular amastigotes, which correspond to the predominant parasite stage in the chronic phase of Chagas disease.
European journal of medicinal chemistry
Fanny Palace-Berl Kerly F M Pasqualoto Bianca Zingales Carolina Borsoi Moraes Mariana Bury Caio Haddad Franco Adelson Lopes da Silva Neto Joao Sussumu Murayama Solange Lessa Nunes Marcelo Nunes Silva Leoberto Costa Tavares
25263283
A Lanthanide MOF Thin Film Fixed with Co3 O4 Nano Anchors as a Highly Efficient Luminescent Sensor for Nitrofuran Antibiotics.
Nitrofurans are a group of widely used veterinary antibiotics, which have been banned due to antibiotics pollution. Development of a rapid and effective method for the detection of nitrofuran antibiotics (NFAs) is an important challenge. Herein, we designed a chemical sensor based on a thin film composed of the lanthanide metal organic framework (Ln MOF) [Eu2 (BCA)3 (H2 O)(DMF)3 ]0.5DMFH2 O}n (Eu BCA, in which BCA is 2,2' biquinoline 4,4' dicarboxylate) coated on a cost effective stainless steel wire mesh (SSWM) by Co3 O4 nano anchor fixation method. The MOF coatings were well adhered to the SSWM, resulting in a three dimensional porous, flexible, and processable sensor. The structure of the as prepared MOF thin film was confirmed by powder X ray diffraction (PXRD) and the surface morphology was examined by scanning electron microscopy (SEM) Significantly, the Eu BCA thin film was highly selective and sensitive to NFAs, and yet remained unaffected by other common antibiotics that may be present. The limits of detection for nitrofurantoin (NFT) and nitrofurazone (NFZ) are 0.21 and 0.16 mm, respectively. NFAs were also successfully detected in water from the Pearl River in Guangzhou, and from bovine serum samples. Hence, the reported Ln MOF thin film is a promising sensor for the detection of NFAs, thereby helping to protect human beings from all manner of hazards that arise from the abuse of antibiotics in livestock breeding.
Chemistry
Feng Zhang Hua Yao Tianshu Chu Gaowei Zhang Yi Wang Yangyi Yang
51704338
Nanocarbon material supported conducting poly(melamine) nanoparticle modified screen printed carbon electrodes for highly sensitive determination of nitrofuran drugs by adsorptive stripping voltammetry
AbstractThe toxicity of nitrofuran drugs has attracted great attention, and the reported electroanalytical methods suffered limited sensitivity. In this work, a sensitive electrochemical assay in the cathodic region is developed to determine four nitrofuran derivatives, including nitrofurantoin (NFT) nitrofurazone (NFZ) furaltadone (FTD) and furazolidone (FZD) The screen printed carbon electrode (SPCE) was used as the electrode substrate, and the sensing surface was composed of multi walled carbon nanotube (MWCNT) and conducting poly(melamine) (PME) The overoxidation pretreated MWCNTs affect the surface morphology of the electrodeposited PME and, thus, the interaction with nitrofuran drugs. The characteristics of the nanocomposite modified electrode surfaces were well characterized by field emission scanning electron microscopy (FE SEM) X ray photoelectron spectroscopy (XPS) and surface water contact angle experiments. The nanocomposite modified electrodes exhibited excellent adsorption and electrochemical reduction of nitrofurans by cyclic voltammetry. The proposed assay exhibited a linear range of sub micro to micro molar concentrations for the four drugs under the optimized differential pulse voltammetric (DPV) technique. The detection limits were found to be in the nanomolar ranges. The developed assay was applied to detect NFT in two real samples, and the results showed good recoveries that ranged from 99.0 to 104.8% and 98.0 to 103.2% for milk and lake water samples, respectively. Graphical abstract
Analytical and Bioanalytical Chemistry
Shao-Hua Chiu Ya-Ling Su Anh V T Le Shu-Hua Cheng
55042278
Development of Antibodies and Immunoassays for Monitoring of Nitrofuran Antibiotics in the Food Chain
Nitrofurans are a broad group of drugs once widely used for treatment of microbial and protozoal infections in many livestock species. However, as concerns grew globally with regard to the potentially carcinogenic and mutagenic effects of their residues in foods, they have been banned from use in many parts of the world. In order to monitor compliance to these bans it is essential to have fitfor purpose testing methods. Immunoassays are the screening tool of choice for many testing laboratories due to their relative low cost, ease of use and high sensitivity. As is the case with all immunoassays, the most important reagents required are high quality, high affinity antibodies that exhibit the required sensitivity and specificity. Generating such antibodies for the nitrofuran family of compounds has required a great deal of effort in the design of immunogens, as the compounds, due to size, are not capable of eliciting an immune response in hosts and are not easily conjugated to carrier proteins. This article reviews the range of strategies used to successfully generate suitable antibodies to a wide range of these drugs and their metabolites. In addition, the platform technologies for nitrofuran detection have moved from simple enzyme linked immunosorbent assay (ELISA) based procedures to more sophisticated multiplexing systems which can undertake faster and broader spectrum testing for the parent drugs and their metabolites. Reviews of the technologies used for immunochemical detection of the nitrofurans and of commercially available test kits are also presented.
Kevin M Cooper Terence L Fodey Katrina Campbell Christopher T Elliott
4712210
Reverse Solvatochromism of Imine Dyes Comprised of 5 Nitrofuran 2 yl or 5 Nitrothiophen 2 yl as Electron Acceptor and Phenolate as Electron Donor.
Eight compounds with phenols as electron donating groups and 5 nitrothiophen 2 yl or 5 nitrofuran 2 yl acceptor moieties in their molecular structures were synthesized. The crystalline structures of six compounds were obtained. Their corresponding phenolate dyes were studied in 29 solvents and the data showed that in all cases a reverse solvatochromism occurred. The results are explained in terms of the ability of the medium to stabilize the electronic ground and excited states of the probes to different extents. The frontier molecular orbitals were analyzed for the protonated and deprotonated forms of the compounds. The calculated geometries are in agreement with the X ray structures determined for the compounds and it was verified that after their deprotonation an increase in the electron delocalization occurs. Radial distribution functions were calculated for the dyes in water and n hexane to analyze different solvation patterns resulting from the interaction of the solvents with the dyes. Data obtained by using the Catalan multiparameter equation revealed that the medium acidity is responsible for hypsochromic shifts, whereas the solvent basicity, polarizability, and dipolarity contributed to bathochromic shifts of the solvatochromic band of these dyes. Two model "hybrid cyanine" dyes were used in the design of simple experiments to demonstrate that the solvatochromic behavior of these dyes in solution can be tuned with careful consideration of the properties of the medium.
Chemistry
Carlos E A de Melo Celso R Nicoleti Marcos Caroli Rezende Adailton Joao Bortoluzzi Renata da S Heying Robson da S Oliboni Giovanni Finoto Caramori Vanderlei Gageiro Machado
105293535
New 5 arylamino 4 (5 nitrofuran 2 yl)pyrimidines as promising antibacterial agents
A facile synthetic approach to 5 arylamino 4 (5 nitrofuran 2 yl)pyrimidines by the Buchwald Hartwig cross coupling with various anilines has been developed. All synthesized compounds demonstrated a significant level of in vitro antibacterial activity against Neisseria gonorrhoeae, Streptococcus pyogene and Staphylococcus aureus, including their drug resistant strains, which is much higher than that of the commercial drug Spectinomycin.
Egor V Verbitskiy Svetlana A Baskakova N A Gerasimova N P Evstigneeva Natal'ya V Zil'berberg Nikolay V Kungurov Marionella A Kravchenko Gennady L Rusinov Oleg N Chupakhina Valery N Charushin