Chloramphenicol Derivatives Research Articles

Effects of florfenicol on the immune responses and the interferon-inducible genes in broiler chickens under the impact of E. coli infection

Florfenicol (FFC) as a chloramphenicol's derivative is a special broad-spectrum antibiotic that was used in veterinary clinics. In the present study, we investigated the effect of different doses of FFC on the humoral immune response of broiler chickens to Newcastle disease virus (NDV) vaccine under the impact of E. coli infection. In addition, the expression of the interferon-inducible genes (IRF7, 2'-5'OAS and Mx1) were analyzed in the spleen tissue of these chickens using quantitative real-time PCR (qRT-PCR). The non-treated group with FFC and non-infected with E. coli had the highest immune responses against NDV compared with the FFC treated groups. In the case of E. coli infection, the group treated with FFC (30 mg/Kg BWt) showed lower NDV HI and IgG ELISA Ab levels compared to the group treated with FFC (60 mg/Kg BWt). A dose dependent up-regulation was observed in the level of the interferon-alpha pathway related genes (IRF7 and 2'-5'OAS) in the FFC treated groups compared to the non-treated group. At the slaughter time, the numbers of adipocyte in the bone marrow were significantly higher with moderate atrophy of the hematopoietic lineages in the FFC treated birds compared to the non-treated birds. These results indicated that this FFC dosage dependent increase in the humoral immune responses against NDV vaccine could be attributed to its efficient therapeutic effect on the E. coli infection. However, the increase in the FFC dosage can negatively but temporarily affect the chicken body weights. Additionally, it can exert up regulation effect on the chicken innate immune response with moderate hypoplasia of the bone marrow cells.

Comparison of Influence of Gamma Rays and E-beam on Some Chloramphenicol Derivatives

Comparison of Influence of Gamma Rays and E-beam on Some Chloramphenicol Derivatives

Enzymatic regioselective production of chloramphenicol esters

An enzymatic study has been performed in the search for synthetic routes to produce chloramphenicol derivatives through regioselective processes using lipases. Complementary transesterification and hydrolytic reactions have been carried to synthesize chloramphenicol regioisomers. Reaction parameters, such as biocatalyst, solvent, acyl donor, and temperature have been optimised in order to obtain chloramphenicol esters with high yields through acylation processes. Scale-up of the enzymatic reactions (1 g-scale at 0.25 M) and catalyst recycling (up to 10 cycles) have been successfully achieved. Furthermore, monoacylated derivatives at the more hindered secondary position could also be obtained employing hydrolysis processes.

A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol.

Dr adhesins are expressed on the surface of uropathogenic and diffusely adherent strains of Escherichia coli. The major adhesin subunit (DraE/AfaE) of these organelles mediates attachment of the bacterium to the surface of the host cell and possibly intracellular invasion through its recognition of the complement regulator decay-accelerating factor (DAF) and/or members of the carcinoembryonic antigen (CEA) family. The adhesin subunit of the Dr haemagglutinin, a Dr-family member, additionally binds type IV collagen and is inhibited in all its receptor interactions by the antibiotic chloramphenicol (CLM). In this study, previous structural work is built upon by reporting the X-ray structures of DraE bound to two chloramphenicol derivatives: chloramphenicol succinate (CLS) and bromamphenicol (BRM). The CLS structure demonstrates that acylation of the 3-hydroxyl group of CLM with succinyl does not significantly perturb the mode of binding, while the BRM structure implies that the binding pocket is able to accommodate bulkier substituents on the N-acyl group. It is concluded that modifications of the 3-hydroxyl group would generate a potent Dr haemagglutinin inhibitor that would not cause the toxic side effects that are associated with the normal bacteriostatic activity of CLM.

Design, synthesis and ribosome binding of chloramphenicol nucleotide and intercalator conjugates

Molecular modelling based on X-ray structures of the antibiotic drug chloramphenicol bound in a bacterial ribosome has been used for design of chloramphenicol derivatives. Conjugates of the chloramphenicol amine through appropriate linkers to either a pyrene moiety or to a mono- or dinucleotide moiety were designed to improve binding to ribosomes by providing specific interactions in the peptidyl transferase site or to the P-loop in the ribosome. Specific binding of the conjugates were investigated by footprinting analysis using chemical modifications of accessible nucleotides in ribosomal RNA. The pyrene chloramphenicol conjugate shows enhanced binding to the chloramphenicol binding site compared to the native chloramphenicol, whereas the four nucleotide conjugates could not be shown to bind to the chloramphenicol binding site or to the P-loop.

Antibacterial Agents in Mediterranean Finfish Farming: A Synopsis of Drug Pharmacokinetics in Important Euryhaline Fish Species and Possible Environmental Implications

The literature pertaining to the use of registered antibacterial agents in Mediterranean finfish farming is reviewed, with an emphasis on the Greek fish-farming industry. This review provides a scientific resource dedicated to the design of future antibacterial dosing regimes in Mediterranean fish farming, where insufficient supporting information is currently available. This paper addresses the paucity in knowledge concerning pharmacokinetics and the efficacy and environmental impact of commonly used antibacterials needed to direct future research and promote good practices in the euryhaline fish farming industry. Several registered antibacterials are currently available for combating bacterial infections, including tetracyclines, (fluoro) quinolones, potentiated sulfa, penicillin and chloramphenicol derivatives. Based on the available data, oxytetracycline (OTC) and quinolone drugs (oxolinic acid – OA and flumequine – FLU) are the most widely used in Mediterranean aquaculture. As a result these drugs have received the most extensive studies, whereas, there is considerable paucity of reliable data on pharmacokinetic and the depletion characteristics of other drugs used, particularly potentiated sulfa, penicillin derivatives and florfenicol. We find there is incomplete data on drug efficacy and minimum inhibitory concentrations (MIC) for common antibacterials used against the major bacterial pathogens of Mediterranean fish species. Furthermore, a considerable lack of data on environmental drug concentrations around Mediterranean fish farms was also identified, highlighting the need for more extensive environmental studies to monitor contamination in environmental components i.e., water and sediment, and in non-target species (flora and fauna). Prudent selection and use of antibacterials can encourage lower dosage applications, enhance treatment efficacy, and help to minimize contamination of the environment. Selection of readily bioavailable drugs which have low environmental persistence, low aquatic toxicity and high antibacterial efficacy is advised, to reduce potential losses to the environment and associated toxic effects on target species and the development of bacterial resistance. Lack of present data made it impossible to provide thorough and accurate guidance on selection and use of antibacterials and approaches for minimizing environmental impacts for the treatment of major euryhaline aquaculture species.

Detection of chloramphenicol and chloramphenicol glucuronide residues in poultry muscle, honey, prawn and milk using a surface plasmon resonance biosensor and Qflex ® kit chloramphenicol

Immunochemical screening assays using surface plasmon resonance have been developed for chloramphenicol and chloramphenicol glucuronide residues in poultry muscle, honey, prawn and cows’ milk using a sensor chip coated with a chloramphenicol derivative and an antibody. The antibody cross-reacted with chloramphenicol glucuronide 73.8% (poultry), 69.2% (honey), 75.7% (prawn) and 84.8% (milk). There was no cross-reaction with similar drugs or other commonly used antibiotics. The assay allowed the direct analysis of bovine milk (fat content ∼3.5%). Poultry, honey and prawn samples were extracted with ethyl acetate followed by analysis on the biosensor. The decision limits (CCα) for each assay were determined as: poultry (0.005 μg kg −1), honey (0.02 μg kg −1), prawn (0.04 μg kg −1) and milk (0.04 μg kg −1) and the detection capabilities (CCβ) were 0.02, 0.02, 0.07 and 0.05 μg kg −1, respectively. Poultry muscle, honey and milk were spiked at 0.1 μg kg −1 and prawn at 0.15 μg kg −1 and the intra-assay precision ( n = 10) calculated as 10.5, 5.0, 4.6 and 8.8%, respectively. Between run precision ( n = 3) performed at the same levels yielded the following results: 3.0% (poultry), 4.7% (honey), 7.6% (milk) and 5.5% (prawn).

(1R,2R)-1,3-Bis(tert-butyldimethylsilyloxy)-2-(4-hydroxybutanamido)-1-(4-nitrophenyl)propane

The title compound, C25H46N2O6Si2, is a new derivative of chloramphenicol. At 180 K, the structure has Z′ = 2 in space group P21.

443 Effect of clofibrate and alcohol treatment on ethanol metabolic enzymes and lipid peroxidation in the rat liver

A copper-catalyzed protocol for the chemoselective arylation of (1R,2R)-(−)-N-BOC-2-amino-1-(4-nitrophenyl)-1,3-propanediol using triarylbismuth reagents is reported. The reaction operates under simple and mild conditions, shows good functional group tolerance and allows the installation of ortho-, meta-, and para-substituted aryl groups in moderate to good yields. These arylated products are then transformed in two steps into their corresponding N-dichloroacetamide derivatives. This sequence provides an expedient access to 3-O-aryl chloramphenicol derivatives.

ChemInform Abstract: An Approach to Oxazolidin‐2‐ones from the Baylis—Hillman Adducts. Formal Synthesis of a Chloramphenicol Derivative.

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An approach to oxazolidin-2-ones from the Baylis–Hillman adducts. Formal synthesis of a chloramphenicol derivative

In this communication we describe a straightforward and diastereoselective approach to prepare functionalised oxazolidin-2-ones from Baylis–Hillman adducts. A stereoselective synthesis of a highly substituted vicinal aminoalcohol and a formal synthesis of a chloramphenicol derivative are also described.

In Vitro Activity of Thiamphenicol Against Multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy

Thiamphenicol is a derivative of chloramphenicol characterized by a spectrum comparable to that of the parent compound against multiresistant pathogens but showing satisfactory tolerability. The In Vitro activity of thiamphenicol and of 11 comparative drugs against 397 recently isolated antibiotic-resistant and/or invasive pneumococci and 52 multiply-resistant MRSA including 2 VISA strains was determined. Bactericidal activity against Haemophilus influenzae and the post-antibiotic effect on Streptococcus pneumoniae, H. influenzae, Staphylococcus aureus and Escherichia coli were also assessed. Against invasive pneumococci, thiamphenicol and chloramphenicol were the most potent non-β-lactam molecules together with vancomycin and rifampin. Against high-level penicillin-resistant strains phenicol activities were superior to those of cefotaxime, ceftriaxone and imipenem. Against MRSA thiamphenicol and chloramphenicol were second only to the glycopetides and also inhibited the VISA strains. Thiamphenicol showed a significant PAE (0.33 to 2.9h) on all pathogens studied and a powerful bactericidal effect against β-lactamase-positive and -negative H. influenzae. These results indicate a good In Vitro activity of thiamphenicol against difficult-to-treat multiply resistant pathogens.

Organometallic complexes with biological molecules. XI. Solid state and in vivo investigations of some diorganotin(IV)-chloramphenicol and cycloserine derivatives

Diorganotin(IV) derivatives of chloramphenicol, {=D-(-)threo-2,2-dichloro-N-[ β-hydroxy- α-(hydroxymethyl)- β-(4-nitrophenyl)ethyl]acetamide (=Hchloramph)}, and D-cycloserine, {=(R)-4-amino-3-isoxazolidone [=Hcyclos]} have been prepared. The stoichiometries of the obtained compounds were R 2SnClantib and R 2Snantib 2 (antib −1=chloramph −1, R=methyl and phenyl; antib −1=cyclos −1, R=methyl). The solid state configuration of the complexes was investigated by I.R. and Mössbauer spectroscopy, from which structural hypotheses were inferred. In particular, the experimental data suggested monomer structures both for R 2Sn(IV)Clchloramph and R 2Sn(IV)chloramph 2, in which chloramphenicolate anion behaved as monoanionic monodentate ligand through the oxygen atom of the deprotonated secondary alcoholic group, with formation of tetrahedral R 2SnOCl and R 2SnO 2 environments. In R 2Sn(IV)Clcyclos and R 2Sn(IV)cyclos 2 derivatives, Mössbauer spectroscopy, and in particular the narrowness of the full width at half height of the resonant peaks, Γ 1 and Γ 2, suggested the occurrence of two different absorbing tin sites with different environments around the tin(IV) atoms. According to calculations performed by applying the point charge model formalism, one site was constituted by a tin(IV) tetrahedrically coordinated by monoanionic monodentate cycloserinate groups, through the oxygen atom of the resonance stabilised hydroxamate anion, originating R 2SnClO and R 2SnO 2 polyhedrons both in R 2Sn(IV)Clcyclos and R 2Sn(IV)cyclos 2, respectively. The second site would correspond to a tin(IV) in a polymeric octahedral configuration with Me 2SnCl 2ON and Me 2SnO 2N 2 environments, in Me 2Sn(IV)Clcyclos and Me 2Sn(IV)cyclos 2 derivatives, respectively, in which the second donor atoms was the amino nitrogen atom. 1H and 13C NMR spectra, of both chloramphenicol and its diorganotin(IV) derivatives were carried in DMSO-d 6 solution, in which R 2Sn(IV)Clchloramph and R 2Sn(IV)chloramph 2 underwent total, (R=Me), or partial, (R=Ph), dissociation. As far as the organotin(IV)-D-cycloserine derivatives were concerned, 1H and 13C NMR spectra, also carried out for the free D-cycloserine, showed that, owing to the coordinating properties of the solvent, octahedral and trigonal bipyramidal isomers were present in DMSO solution of Me 2Sn(IV)Clcyclos and Me 2Sn(IV)cyclos 2. Finally, the cytotoxic activity of the free chloramphenicol, D-cycloserine and of their dimethyltin(IV) derivatives has been investigated towards Ciona intestinalis and Ascidia malaca fertilised eggs, at different developing stages.

Chloramphenicol sensor based on an in situ imprinted polymer

We have recently developed a liquid-chromatography (LC)-based sensor for the broad-spectrum antibiotic chloramphenicol which relies upon the displacement of a chloramphenicol (CAP) dye conjugate from a molecularly imprinted polymer by the drug. The sensor was immune to interference from various chloramphenicol derivatives and ≈60% as responsive to thiamphenicol (TAM), an almost identical analog. The system showed a linear response to the drug over the 3–1000 μg ml −1 range; it was therefore effective both below and above the therapeutic (10–20 μg/ml −1 serum range, being potentially toxic above 25 μg ml −1). The sensor effectively detected CAP extracted from serum with a 3 σ detection limit of ca. 5 μg ml −1. We have further simplified the construction of the sensor by the use of an in-situ imprinting technique wherein the polymer is formed inside an LC column. These columns are far simpler to prepare and, although their characteristics are somewhat different, their performance is comparable with that of the bulk-polymerized materials. The capacity of the columns is significantly less than that of packed columns but their ability to separate TAM and CAP is slightly better. The best of these columns showed a fairly linear response ( r 2=0.95, n=3) for 0–30 μg ml −1 CAP with a detection limit of ca. 3 μg ml −1. The column also showed a linear ( r 2=0.96, n=3), although lesser response to TAM over a similar concentration range. As with the bulk-polymerized material, the system showed minimal response to the diacetyl derivative CAP-DA.

The identification and characterisation of chloramphenicol-aldehyde, a new human metabolite of chloramphenicol.

The toxic aldehyde derivative of chloramphenicol has previously been reported as a metabolic product only in the rat. Chloramphenicol-aldehyde has been synthesised and characterised and shown to exist in at least two forms, possibly due to rearrangement within the molecule. The authenticated compound has been used to identify chloramphenicol-aldehyde as a metabolic product excreted in the urine of children treated with chloramphenicol.

Synthesis and antimicrobial activity of chloramphenicol derivatives based on N-[2-hydroxypropyl]methacrylamide copolymers having oligopeptides spacers

Synthesis and antimicrobial activity of chloramphenicol derivatives based on N-[2-hydroxypropyl]methacrylamide copolymers having oligopeptides spacers

ChemInform Abstract: Synthesis of Ester Derivatives of Chloramphenicol by Lipase‐Catalyzed Transesterification in Organic Solvents.

ChemInform Abstract: Synthesis of Ester Derivatives of Chloramphenicol by Lipase‐Catalyzed Transesterification in Organic Solvents.

Synthesis of ester derivatives of chloramphenicol by lipase-catalyzed transesterification in organic solvents

Synthesis of ester derivatives of chloramphenicol by lipase-catalyzed transesterification in organic solvents

Polymeric Derivatives of Chloramphenicol and Their Antibacterial Properties

Abstract The polymerizable derivatives of chloramphenicol were prepared and free-radical copolymerized with acrylamide, methacrylic acid, and 2-(dimethylamino)ethyl methacrylate in order to obtain polymers with pharmacological activity. The monomeric and polymeric derivatives were subjected to antibacterial activity tests against Bacillus polymyxa.

Receptor-mediated in vitro gene transformation by a soluble DNA carrier system.

We present, here, evidence that foreign DNA can be specifically delivered to cells by a soluble carrier system that takes advantage of receptor-mediated endocytosis. Our experiments were based on the following concepts: hepatocytes possess a unique receptor that binds and internalizes galactose-terminal (asialo-)glycoproteins; DNA can bind to polycations in a strong but noncovalent manner forming soluble complexes; and the gene for chloramphenicol acetyltransferase, a bacterial enzyme that acetylates chloramphenicol, is not present in mammalian cells. We coupled asialoorosomucoid (ASOR) to poly-L-lysine to form an asialoorosomucoid-poly-L-lysine conjugate. The plasmid, pSV2 CAT, was complexed to the conjugate in a molar ratio of 1:2. To test this complex, a model system was used consisting of hepatoma cell lines, Hep G2, asialoglycoprotein receptor (+), and SK-Hep 1, receptor (-). Each cell line was incubated with filtered ASOR X poly-L-lysine X DNA complex, or controls consisting of DNA plus ASOR, DNA plus poly-L-lysine, or DNA alone. Cells were assayed for the presence of chloramphenicol acetyltransferase activity as a measure of gene transformation. SK-Hep 1, receptor (-) cells, produced no detectable acetylated chloramphenicol derivatives under any condition. However, Hep G2, receptor (+) cells, incubated with the ASOR X poly-L-lysine X DNA complex were transformed as indicated by the presence of chloramphenicol acetyltransferase activity (0.028 chloramphenicol acetyltransferase units/10(6) cells). Mixtures of individual components of the complex failed to transform these cells. Competition by a 10-fold excess of ASOR prevented gene transformation by the ASOR X poly-L-lysine X DNA complex.