Objective:To explore various unexplored locations where Penicillium spp.would be available and study the production of penicillin from the isolated Penicillium spp.in different media with altered carbohydrate source.M...Objective:To explore various unexplored locations where Penicillium spp.would be available and study the production of penicillin from the isolated Penicillium spp.in different media with altered carbohydrate source.Methods:The collected soil samples were screened for the isolation of Penicillium chrysogenum(P.chrysogenum) by soil dilution plate.The isolated Penicillium species were further grown in different production media with changes in the carbohydrate source.The extracted penicillin from various isolates was analyzed by HPLC for the efficacy of the product.Further the products were screened with various bacterial species including methicillin resistant Staphylococcus aureus(MRSA).And the work was extended to find the possible action on MRSA,along with characterization using other pathogens.Results:From the various soil and citrus samples used for analysis,only the soil sample from Government General Hospital of Bangalore,India,and Sanjay Gandhi Hospital,Bangalore,India,showed some potential growth of the desired fungi P.chrysogenum.Different production media showed varied range of growth of PenicilUum.Optimum production of penicillin was obtained in maltose which proved maximum zone of inhibition during assay.Characterization of penicillin on pathogens,like wild Escherichia coli strain,Klebsiella spp.,and MRSA,gave quite interesting results such as no activity on the later strain as it is resistant.HPLC data provided the analytical and confirmation details of the penicillin produced.Accordingly,the penicillin produced from the soil sample of Government General Hospital had the high milli absorbance unit of 441.5 mAu compared with that of the penicillin produced from Sanjay Gandhi Hospital sample,8S.S2 mAu.Therefore,there was a considerable change in quantity of the penicillin produced from both the samples.Conclusions: The Penicillium spp.could be possibly rich in hospital contaminants and its environments.This research focuses on various unexplored sources of medical ailments,and also shows that the growth of penicillin is high in maltose rich media that could possibly enhance the growth.展开更多
Partition behavior of penicillins G and V was studied in a novel three-liquid-phase extraction system,which is composed of butyl acetate (BA),polyethylene glycol (PEG),ammonia sulfate (NH4)2SO4 and water (H2O). The ma...Partition behavior of penicillins G and V was studied in a novel three-liquid-phase extraction system,which is composed of butyl acetate (BA),polyethylene glycol (PEG),ammonia sulfate (NH4)2SO4 and water (H2O). The main components in the top,middle and bottom phases are butyl acetate,polyethylene glycol aqueous solution and ammonia sulfate aqueous solution,respectively. Some parameters such as partition coefficients Di/j and mass fractions Ei of penicillins G and V were determined at the room temperature,respectively. Experimental efforts have been made to investigate the partition behavior of penicillin in the three-liquid-phase extraction system,including initial concentrations of phase-forming components PEG and (NH4)2SO4,PEG molecular weight,pH,initial concentration of penicillin. The results indicated that penicillins G and V have the similar partition behavior. They preferentially distribute into the middle phase with the increase of initial concentration of phase-forming components and into the top phase with the decrease of pH,while partition coefficient Dm/b is hardly affected by pH value. The variation of PEG molecular weight has little effect on mass fractions of penicillin. The increase of initial concentration of penicillins G and V could lead to the increase of Dt/b,Dm/b and the decrease of Dt/m,while their mass fractions in all phases were almost independent on their initial concentrations.展开更多
The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence ...The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).展开更多
A four new penicillinate complexes were prepared through the chemical interactio ns of penicillin potassium salt (Pin) with YCl 3, GeCl 4, WCl 6 and SiCl 4 m etal ions. These metal complexes were characterized using s...A four new penicillinate complexes were prepared through the chemical interactio ns of penicillin potassium salt (Pin) with YCl 3, GeCl 4, WCl 6 and SiCl 4 m etal ions. These metal complexes were characterized using spectroscopic techniqu es (e.g. 1H-NMR, infrared, electronic UV-Vis) as well as elemental, cond uctivity, and magnetic measurements. The molar conductance values were highly, s howing their electrolytic nature. The magnetic and electronic study strongly rec ommends the octahedral geometry of all penicillinate complexes. A monomeric stru ctures of Pin complexes are proposed with octahedral coordinated metals ions. Th e metal ions are coordinated toward Pin as tridentate ligand through the amide a nd β-lactam carbonyls and a carboxylate group from penicillin. The in vitro antimicrobial activity of all the complexes, at concentrations in μg·mL^-1 , was screened against four bacterial pathogens, namely, Bacillus subtilis , Escherichia coli, Pseudomonas aeruginosa , and Staphylococcus aureus , and two kinds of fungi Aspergillus flavus and Candida albicans showed better activi ty compared to parent drug and control drug. The anti-cancer inhibition of the tungsten(Ⅵ) complex was assessed against the human hepato cellular carcinoma (H epG-2) tumor cell line with IC50 value is 646 μg·mL^-1 .展开更多
The mixture of neutral phosphorus esters and butyl acetate (BA) can be used, as the extractant for the extraction of penicillin G. The extraction equilibrium pH can be increased to pH3—4 due to the stronger extractio...The mixture of neutral phosphorus esters and butyl acetate (BA) can be used, as the extractant for the extraction of penicillin G. The extraction equilibrium pH can be increased to pH3—4 due to the stronger extraction capability of the solvent mixture, instead of pH1.8—2.2 with butyl acetate as solvent. The experimental results indicate that the total recovery of penicillin G can reach 96.6% with the new extraction process, which is 5—6% higher than that obtained with the traditional process using BA as solvent at pH1.8—2.2.展开更多
Reductive debromination of anhydro-6-(R)-hydroxycthyl-6-(R) 7 by zinc in ammonium acetate gave 9 in 81% yield with high stcreosclectivity of 6-(α):6-(β)= 13:
Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymeri...Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current understanding of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the b-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the b-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.展开更多
The effect of penicillin-G on Flavobacterium psychrophilum, the cause of bacterial coldwater disease, was evaluated in 15 min and overnight exposures. Separate tests evaluated the effect of increasing doses of penicil...The effect of penicillin-G on Flavobacterium psychrophilum, the cause of bacterial coldwater disease, was evaluated in 15 min and overnight exposures. Separate tests evaluated the effect of increasing doses of penicillin-G to rainbow trout Oncorhynchus mykiss eggs, fingerlings, and adults. Rainbow trout eggs were exposed for 1 h to penicillin doses of 0, 250, 500, 1,000, 10,000, 50,000, or 100,000 IU/mL. Mean percent hatch ranged from 64.6% to 75.1%, and did not significantly differ among the treatments. Fingerlings were injected intraperitoneally (i.p.) with 200 μL of 0, 1, 10, 100, 1,000, 10,000, 100,000, or 500,000 IU/mL. Probit analysis resulted in a LD10 (lethal dose for 10% of injected fish) of 52,868 IU/mL (95% confidence limits: 31,522 - 69,490 IU/mL) and a LD50 of 131,466 IU/mL (113,095 - 157,878 IU/mL). Brood stock were injected (i.p.) with 200 μL of penicillin at concentrations of 0 (control), 10,000, 50,000, 100,000, 200,000, 400,000, or 800,000 IU/mL. Mortality ranged from 0% to 7% (50,000 IU/mL treatment) and did not significantly differ among treatments. In 28 h exposure tests, penicillin concentrations of ≥ 333 IU/mL were required to completely suppress growth of F. psychrophilum. In 15 min exposures, ≥ 10,000 IU/mL were needed to achieve the same result. Tests indicated that rainbow trout eggs can tolerate 1 h exposures to penicillin-G concentrations as high as 100,000 IU/mL, and that brood fish can tolerate injections of at least 800,000 IU/mL. Fingerling data however, suggested that injection of doses greater than 10,000 IU/mL can be toxic. The data suggests rainbow trout eggs or brood can tolerate high doses of penicillin-G that could be used for controlling the transfer of F. psychrophilum to hatcheries receiving eggs.展开更多
A simple inexpensive method of monitoring hydrolysis of an antibiotic penicillin G (pen G) and subsequent enzyme detection using gold nanoparticles is presented. Gold nanoparticles capped with Cetyl trimethyl ammonium...A simple inexpensive method of monitoring hydrolysis of an antibiotic penicillin G (pen G) and subsequent enzyme detection using gold nanoparticles is presented. Gold nanoparticles capped with Cetyl trimethyl ammonium bromide (CTAB) are synthesized using chemical route. The particles could be used for detection of Penicillin G acylase (PGA) enzyme by incorporating hydrolysis reaction with pen G. This hydrolysis reaction leads to a shift in the surface plasmon band of gold nanoparticles from 527 nm to 545 nm accompanied by a visual colorimetric change in the solution from red to blue. The process is attributed to aggregation of nanoparticles caused due to displacement of CTAB bilayer by byproducts of the hydrolysis reaction. It is proposed that the presence of 0.007 mg/ml of PGA can be detected by a color change of gold nanoparticles solution without requiring any complicated instrument or highly trained operator to conduct the test. The method could also identify the presence of different penicillins by showing different spectral shifts. Thus the work presented here would be useful not only for the detection of the pharmaceutically important drug Pen G, but also represents a general methodology for the detection of enzymes, eg PGA.展开更多
We previously demonstrated that brief nonkilling neutrophil exposure diminishes the binding affinity of S. aureus penicillin-binding protein (PBP) 2. We sought to investigate further the role of the neutrophil in the ...We previously demonstrated that brief nonkilling neutrophil exposure diminishes the binding affinity of S. aureus penicillin-binding protein (PBP) 2. We sought to investigate further the role of the neutrophil in the alteration of antimicrobial activity and its interaction with PBP-2 by studying the activity of cefotaxime, which highly binds to PBP 2, and cephalexin, which minimally binds to PBP 2. Using S. aureus, cultured in vitro in sterile-filtered normal and neutrophil depleted abscess fluid, we sought to demonstrate an in vivo significance of the neutrophil effect upon the activity of antimicrobials that target PBP-2 by studying the same antimicrobials in an experimental S. aureus abscess. Rats were implanted with perforated tissue cages and infected with S. aureus;some rats were neutrophil depleted by mechlorethamine. Abscess fluids from normal and neutropenic abscesses were harvested, pooled, sterile-filtered and stored for the time-kill studies. Treatment studies were performed by administering either 300 μg/kg/d cefotaxime or cephalexin for 7 days in other rats with 24 hour-old tissue-cage S. aureus abscesses. In time-kill studies, cefotaxime was highly active against stationary phase S. aureus in MHB and in neutropenic abscess fluid, but less active in the non-neutropenic abscess fluid (p 10 kill, p = 0.029 vs. 0.81 ± 2.5, p = NS). These data suggest that neutrophil exposure, which diminishes S. aureus PBP-2 binding affinity [or total quantity], also adversely affects the antimicrobial activity of cefotaxime, which binds to PBP-2, as compared to cephalexin. Altered PBP targets from neutrophil exposure may be a mechanism of antimicrobial resistance within abscesses.展开更多
Objective To develop a rapid multi-residue assay for detecting 16 demanded by the European Union (EU). Methods A recombinant penicillin-binding protein(PBP)2x* from Streptococcus pneumoniae R6 was expressed in vitro a...Objective To develop a rapid multi-residue assay for detecting 16 demanded by the European Union (EU). Methods A recombinant penicillin-binding protein(PBP)2x* from Streptococcus pneumoniae R6 was expressed in vitro and six β-lactams were conjugated to HRP by four methods.A rapid multi-residue assay for β-lactams was established with PBP2x* and HRP-conjugate. Results PBP2x* was expressed and purified successfully and the ideal HRP-conjugate was identified. The multi-residue assay was developed.After optimization,penicillin G,ampicillin,amoxicillin, cloxacillin,dicloxacillin,oxacillin,nafcillin,cephalexin,ceftiofur,cefaIonium,cefquinome,cefazolin, cefoperazone,cephacetrile,and cephapirin can be detected at levels below MRL in milk with simple pretreatment. Conclusion This assay developed can detect all 16 β-lactams demanded by the European Union(EU). The whole procedure takes only 45 min and can detect 42 samples and the standards with duplicate analysis.展开更多
Penicillin G acylase(PGA) was immobilized on the magnetic hydrophilic polymer microspheres with average pore size of 17.1 nm,specific surface area of 128.2 m^2/g and saturate magnetization of 6.4 emu/g.The 96.7%ampici...Penicillin G acylase(PGA) was immobilized on the magnetic hydrophilic polymer microspheres with average pore size of 17.1 nm,specific surface area of 128.2 m^2/g and saturate magnetization of 6.4 emu/g.The 96.7%ampicillin yield with 1.60 of the synthesis/hydrolysis(S/H) ratio from 6-aminopenicillanic acid(6-APA) and D-(-)-alpha-phenylglycine methyl ester(D-PGME) can be achieved using the resultant magnetic biocatalyst in ethylene glycol,where only 82.1%yield with 1.40 of the S/H ratio was obtained using the free PGA under the identical reaction conditions.The immobilized PGA can be separated magnetically and recycled for five times without obvious loss of its catalytic activity.展开更多
Bovine mastitis caused by Staphylococcus aureus is difficult to treat because of increasing resistance against antibiotics, especially penicillin. β-Lactamase and biofilm are responsible for penicillin resistance of ...Bovine mastitis caused by Staphylococcus aureus is difficult to treat because of increasing resistance against antibiotics, especially penicillin. β-Lactamase and biofilm are responsible for penicillin resistance of S. aureus. The aim of this study was to investigate the β-lactamase activity and biofilm formation capacity of 37 penicillin-resistant S. aureus strains(35 were blaZ positive and 2 were blaZ negative) from bovine mastitis in Gansu Province, China, as well as to measure the intercellular adhesion genes icaA and icaD of these strains. β-Lactamase Test Kit was used to determine the β-lactamase activity, biofilm formation was tested by semi-quantitative adherence assay method. Moreover, the presence of icaA and icaD were measured by PCR. A total of 32 penicillin-resistant S. aureus strains, including the two blaZ-negative strains, were identified as β-lactamase producers. All tested S. aureus isolates produced biofilm in the microtiter plate assay. Meanwhile, all these strains were PCR-positive for the ica locus, icaA and icaD. The study indicated high prevalence of β-lactamase activity, biofilm-forming capacity, and the ica genes among the penicillin-resistant S. aureus isolates, and implied that S. aureus resistant to penicillin was attributed to multiple mechanisms.展开更多
The hydrophilic, macroporous and beaded ternary copolymer of glycidyl methacrylate (GMA)/methacrylamide(MA)/N,N′-methylene-bis(acrylamide)(MBAA)was synthesized using the industrial agents by inverse suspension polyme...The hydrophilic, macroporous and beaded ternary copolymer of glycidyl methacrylate (GMA)/methacrylamide(MA)/N,N′-methylene-bis(acrylamide)(MBAA)was synthesized using the industrial agents by inverse suspension polymerization. The apparent activity of the immobilized penicillin G acylase reached 1096 IU/g for hydrolysis penicillin G on the beads with diameter of 0.11-0.13 mm, and it changed hardly after 50 cycles. It can be expected to be a good potential in industrial application.展开更多
The effect of penicillin on the human peripheral lymphocytes was studied by steady fluorescent technique and ratiometric fluorescence dye, Fura-2. The change of the free calcium concentration in cytosol was examined u...The effect of penicillin on the human peripheral lymphocytes was studied by steady fluorescent technique and ratiometric fluorescence dye, Fura-2. The change of the free calcium concentration in cytosol was examined under different conditions. A characterization of Fura-2-Ca interaction in an isotonic saline solution showed that Ca2+ formed a 1*1 Fura-2-Ca complex with the apparent dissociation constant 1.81×10-7 mol/L. The mechanism, by which penicillin induced the decrease of [Ca2+]i , was discussed in detail. The low dose of penicillin might modify the lymphocytes’ immunology response by interfering the increase in the intracellular free calcium concentration.展开更多
The extraction of penicillin G by ionic liquid[Bmim]PF_6 has exhibited promising prospect.The stability of penicillin G is crucial for developing a green ionic liquid-based extraction technology.In this work,the stabi...The extraction of penicillin G by ionic liquid[Bmim]PF_6 has exhibited promising prospect.The stability of penicillin G is crucial for developing a green ionic liquid-based extraction technology.In this work,the stability of penicillin G in[Bmim]PF_6 was systematically investigated.The results showed the stability of penicillin G was significantly influenced by pH and temperature.It tended to be more stable when pH value increased from 1.5 to 4.0 and the temperature gradually decreased.The half-life(t_(1/2))of penicillin G in[Bmim]PF_6 was 17.7 h in the optimal technological condition(pH 2.0 and 10°C),which is enough for the requirement of extraction technology.The reaction of penicillin G in[Bmim]PF_6 followed the first order kinetics in the pH range 2.0–4.0.Three isomers of penicillin G were found through rearrangement at pH 2.0,and their structures were not affected by temperature.展开更多
文摘Objective:To explore various unexplored locations where Penicillium spp.would be available and study the production of penicillin from the isolated Penicillium spp.in different media with altered carbohydrate source.Methods:The collected soil samples were screened for the isolation of Penicillium chrysogenum(P.chrysogenum) by soil dilution plate.The isolated Penicillium species were further grown in different production media with changes in the carbohydrate source.The extracted penicillin from various isolates was analyzed by HPLC for the efficacy of the product.Further the products were screened with various bacterial species including methicillin resistant Staphylococcus aureus(MRSA).And the work was extended to find the possible action on MRSA,along with characterization using other pathogens.Results:From the various soil and citrus samples used for analysis,only the soil sample from Government General Hospital of Bangalore,India,and Sanjay Gandhi Hospital,Bangalore,India,showed some potential growth of the desired fungi P.chrysogenum.Different production media showed varied range of growth of PenicilUum.Optimum production of penicillin was obtained in maltose which proved maximum zone of inhibition during assay.Characterization of penicillin on pathogens,like wild Escherichia coli strain,Klebsiella spp.,and MRSA,gave quite interesting results such as no activity on the later strain as it is resistant.HPLC data provided the analytical and confirmation details of the penicillin produced.Accordingly,the penicillin produced from the soil sample of Government General Hospital had the high milli absorbance unit of 441.5 mAu compared with that of the penicillin produced from Sanjay Gandhi Hospital sample,8S.S2 mAu.Therefore,there was a considerable change in quantity of the penicillin produced from both the samples.Conclusions: The Penicillium spp.could be possibly rich in hospital contaminants and its environments.This research focuses on various unexplored sources of medical ailments,and also shows that the growth of penicillin is high in maltose rich media that could possibly enhance the growth.
基金Supported by the National Natural Science Foundation of China (No.20236050 20406021)+1 种基金 The Innovative Research Group Fund (No. 20236050 20406021)
文摘Partition behavior of penicillins G and V was studied in a novel three-liquid-phase extraction system,which is composed of butyl acetate (BA),polyethylene glycol (PEG),ammonia sulfate (NH4)2SO4 and water (H2O). The main components in the top,middle and bottom phases are butyl acetate,polyethylene glycol aqueous solution and ammonia sulfate aqueous solution,respectively. Some parameters such as partition coefficients Di/j and mass fractions Ei of penicillins G and V were determined at the room temperature,respectively. Experimental efforts have been made to investigate the partition behavior of penicillin in the three-liquid-phase extraction system,including initial concentrations of phase-forming components PEG and (NH4)2SO4,PEG molecular weight,pH,initial concentration of penicillin. The results indicated that penicillins G and V have the similar partition behavior. They preferentially distribute into the middle phase with the increase of initial concentration of phase-forming components and into the top phase with the decrease of pH,while partition coefficient Dm/b is hardly affected by pH value. The variation of PEG molecular weight has little effect on mass fractions of penicillin. The increase of initial concentration of penicillins G and V could lead to the increase of Dt/b,Dm/b and the decrease of Dt/m,while their mass fractions in all phases were almost independent on their initial concentrations.
文摘The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).
文摘A four new penicillinate complexes were prepared through the chemical interactio ns of penicillin potassium salt (Pin) with YCl 3, GeCl 4, WCl 6 and SiCl 4 m etal ions. These metal complexes were characterized using spectroscopic techniqu es (e.g. 1H-NMR, infrared, electronic UV-Vis) as well as elemental, cond uctivity, and magnetic measurements. The molar conductance values were highly, s howing their electrolytic nature. The magnetic and electronic study strongly rec ommends the octahedral geometry of all penicillinate complexes. A monomeric stru ctures of Pin complexes are proposed with octahedral coordinated metals ions. Th e metal ions are coordinated toward Pin as tridentate ligand through the amide a nd β-lactam carbonyls and a carboxylate group from penicillin. The in vitro antimicrobial activity of all the complexes, at concentrations in μg·mL^-1 , was screened against four bacterial pathogens, namely, Bacillus subtilis , Escherichia coli, Pseudomonas aeruginosa , and Staphylococcus aureus , and two kinds of fungi Aspergillus flavus and Candida albicans showed better activi ty compared to parent drug and control drug. The anti-cancer inhibition of the tungsten(Ⅵ) complex was assessed against the human hepato cellular carcinoma (H epG-2) tumor cell line with IC50 value is 646 μg·mL^-1 .
文摘The mixture of neutral phosphorus esters and butyl acetate (BA) can be used, as the extractant for the extraction of penicillin G. The extraction equilibrium pH can be increased to pH3—4 due to the stronger extraction capability of the solvent mixture, instead of pH1.8—2.2 with butyl acetate as solvent. The experimental results indicate that the total recovery of penicillin G can reach 96.6% with the new extraction process, which is 5—6% higher than that obtained with the traditional process using BA as solvent at pH1.8—2.2.
文摘Reductive debromination of anhydro-6-(R)-hydroxycthyl-6-(R) 7 by zinc in ammonium acetate gave 9 in 81% yield with high stcreosclectivity of 6-(α):6-(β)= 13:
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(Grant No.:2017ZX09101001-007).
文摘Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current understanding of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the b-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the b-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.
文摘The effect of penicillin-G on Flavobacterium psychrophilum, the cause of bacterial coldwater disease, was evaluated in 15 min and overnight exposures. Separate tests evaluated the effect of increasing doses of penicillin-G to rainbow trout Oncorhynchus mykiss eggs, fingerlings, and adults. Rainbow trout eggs were exposed for 1 h to penicillin doses of 0, 250, 500, 1,000, 10,000, 50,000, or 100,000 IU/mL. Mean percent hatch ranged from 64.6% to 75.1%, and did not significantly differ among the treatments. Fingerlings were injected intraperitoneally (i.p.) with 200 μL of 0, 1, 10, 100, 1,000, 10,000, 100,000, or 500,000 IU/mL. Probit analysis resulted in a LD10 (lethal dose for 10% of injected fish) of 52,868 IU/mL (95% confidence limits: 31,522 - 69,490 IU/mL) and a LD50 of 131,466 IU/mL (113,095 - 157,878 IU/mL). Brood stock were injected (i.p.) with 200 μL of penicillin at concentrations of 0 (control), 10,000, 50,000, 100,000, 200,000, 400,000, or 800,000 IU/mL. Mortality ranged from 0% to 7% (50,000 IU/mL treatment) and did not significantly differ among treatments. In 28 h exposure tests, penicillin concentrations of ≥ 333 IU/mL were required to completely suppress growth of F. psychrophilum. In 15 min exposures, ≥ 10,000 IU/mL were needed to achieve the same result. Tests indicated that rainbow trout eggs can tolerate 1 h exposures to penicillin-G concentrations as high as 100,000 IU/mL, and that brood fish can tolerate injections of at least 800,000 IU/mL. Fingerling data however, suggested that injection of doses greater than 10,000 IU/mL can be toxic. The data suggests rainbow trout eggs or brood can tolerate high doses of penicillin-G that could be used for controlling the transfer of F. psychrophilum to hatcheries receiving eggs.
文摘A simple inexpensive method of monitoring hydrolysis of an antibiotic penicillin G (pen G) and subsequent enzyme detection using gold nanoparticles is presented. Gold nanoparticles capped with Cetyl trimethyl ammonium bromide (CTAB) are synthesized using chemical route. The particles could be used for detection of Penicillin G acylase (PGA) enzyme by incorporating hydrolysis reaction with pen G. This hydrolysis reaction leads to a shift in the surface plasmon band of gold nanoparticles from 527 nm to 545 nm accompanied by a visual colorimetric change in the solution from red to blue. The process is attributed to aggregation of nanoparticles caused due to displacement of CTAB bilayer by byproducts of the hydrolysis reaction. It is proposed that the presence of 0.007 mg/ml of PGA can be detected by a color change of gold nanoparticles solution without requiring any complicated instrument or highly trained operator to conduct the test. The method could also identify the presence of different penicillins by showing different spectral shifts. Thus the work presented here would be useful not only for the detection of the pharmaceutically important drug Pen G, but also represents a general methodology for the detection of enzymes, eg PGA.
文摘We previously demonstrated that brief nonkilling neutrophil exposure diminishes the binding affinity of S. aureus penicillin-binding protein (PBP) 2. We sought to investigate further the role of the neutrophil in the alteration of antimicrobial activity and its interaction with PBP-2 by studying the activity of cefotaxime, which highly binds to PBP 2, and cephalexin, which minimally binds to PBP 2. Using S. aureus, cultured in vitro in sterile-filtered normal and neutrophil depleted abscess fluid, we sought to demonstrate an in vivo significance of the neutrophil effect upon the activity of antimicrobials that target PBP-2 by studying the same antimicrobials in an experimental S. aureus abscess. Rats were implanted with perforated tissue cages and infected with S. aureus;some rats were neutrophil depleted by mechlorethamine. Abscess fluids from normal and neutropenic abscesses were harvested, pooled, sterile-filtered and stored for the time-kill studies. Treatment studies were performed by administering either 300 μg/kg/d cefotaxime or cephalexin for 7 days in other rats with 24 hour-old tissue-cage S. aureus abscesses. In time-kill studies, cefotaxime was highly active against stationary phase S. aureus in MHB and in neutropenic abscess fluid, but less active in the non-neutropenic abscess fluid (p 10 kill, p = 0.029 vs. 0.81 ± 2.5, p = NS). These data suggest that neutrophil exposure, which diminishes S. aureus PBP-2 binding affinity [or total quantity], also adversely affects the antimicrobial activity of cefotaxime, which binds to PBP-2, as compared to cephalexin. Altered PBP targets from neutrophil exposure may be a mechanism of antimicrobial resistance within abscesses.
基金Supported by the National High Technology Research and Development Program of China （863 Program, No.2006AA02Z211）, the National Natural Science Foundation of China （No.20376034）, the Natural Science Foundation of Jiangsu Province of China （BK2006181）, and the Scientific Research Foundation for Young Teachers in the Higher Education Institutions of Anhui Province of China （2005jq1163）, and the Foundation of Jiangsu Province of China for College Postgraduate Students in Inno-vation Engineering （2007）.
文摘改进青霉素 acylase (PA ) 的共有原子价固定，宏分子的拥挤理论被用于它的固定。到硅石的酶的集体比率的影响，以及，有在装配 PA 的活动的 glutaraldehyde 的激活时间，被学习。在中央毛孔，酶的固定上的β - 出租机动三轮车糊精(β - CD ) 的效果也被调查。当青霉素 acylase 在中央毛孔 covalently 集合了时，分别地，联合收益和相对活动到达了 99.5% 和 92.3% ，是显著的。这里的结果显示拥挤的那个模仿的大分子能显著地改善 covalently 使不能调动的 PA 的表演。
文摘Objective To develop a rapid multi-residue assay for detecting 16 demanded by the European Union (EU). Methods A recombinant penicillin-binding protein(PBP)2x* from Streptococcus pneumoniae R6 was expressed in vitro and six β-lactams were conjugated to HRP by four methods.A rapid multi-residue assay for β-lactams was established with PBP2x* and HRP-conjugate. Results PBP2x* was expressed and purified successfully and the ideal HRP-conjugate was identified. The multi-residue assay was developed.After optimization,penicillin G,ampicillin,amoxicillin, cloxacillin,dicloxacillin,oxacillin,nafcillin,cephalexin,ceftiofur,cefaIonium,cefquinome,cefazolin, cefoperazone,cephacetrile,and cephapirin can be detected at levels below MRL in milk with simple pretreatment. Conclusion This assay developed can detect all 16 β-lactams demanded by the European Union(EU). The whole procedure takes only 45 min and can detect 42 samples and the standards with duplicate analysis.
基金supported by The National Basic Research Program 973 of China(No.2010CB534916)the National Natural Science Foundation of China(Nos.50662004,20564002).
文摘Penicillin G acylase(PGA) was immobilized on the magnetic hydrophilic polymer microspheres with average pore size of 17.1 nm,specific surface area of 128.2 m^2/g and saturate magnetization of 6.4 emu/g.The 96.7%ampicillin yield with 1.60 of the synthesis/hydrolysis(S/H) ratio from 6-aminopenicillanic acid(6-APA) and D-(-)-alpha-phenylglycine methyl ester(D-PGME) can be achieved using the resultant magnetic biocatalyst in ethylene glycol,where only 82.1%yield with 1.40 of the S/H ratio was obtained using the free PGA under the identical reaction conditions.The immobilized PGA can be separated magnetically and recycled for five times without obvious loss of its catalytic activity.
基金supported by the Central Public-Interest Scientific Institution Basal Research Fund,China(1610322015007)the Key Technologies R&D Program of China during the 12th Five-year Plan period(2012BAD12B03)the Natural Science Foundation of Gansu Province,China(145RJYA311)
文摘Bovine mastitis caused by Staphylococcus aureus is difficult to treat because of increasing resistance against antibiotics, especially penicillin. β-Lactamase and biofilm are responsible for penicillin resistance of S. aureus. The aim of this study was to investigate the β-lactamase activity and biofilm formation capacity of 37 penicillin-resistant S. aureus strains(35 were blaZ positive and 2 were blaZ negative) from bovine mastitis in Gansu Province, China, as well as to measure the intercellular adhesion genes icaA and icaD of these strains. β-Lactamase Test Kit was used to determine the β-lactamase activity, biofilm formation was tested by semi-quantitative adherence assay method. Moreover, the presence of icaA and icaD were measured by PCR. A total of 32 penicillin-resistant S. aureus strains, including the two blaZ-negative strains, were identified as β-lactamase producers. All tested S. aureus isolates produced biofilm in the microtiter plate assay. Meanwhile, all these strains were PCR-positive for the ica locus, icaA and icaD. The study indicated high prevalence of β-lactamase activity, biofilm-forming capacity, and the ica genes among the penicillin-resistant S. aureus isolates, and implied that S. aureus resistant to penicillin was attributed to multiple mechanisms.
基金supported by the National Natural Science Foundation of China(No.20564002)the State Key Program of Fundamental Research(No.2004CCA05900).
文摘The hydrophilic, macroporous and beaded ternary copolymer of glycidyl methacrylate (GMA)/methacrylamide(MA)/N,N′-methylene-bis(acrylamide)(MBAA)was synthesized using the industrial agents by inverse suspension polymerization. The apparent activity of the immobilized penicillin G acylase reached 1096 IU/g for hydrolysis penicillin G on the beads with diameter of 0.11-0.13 mm, and it changed hardly after 50 cycles. It can be expected to be a good potential in industrial application.
基金This work was supported by the National Natural Science Foundation of China （No.20575038）the Foundation of Shanxi Provience （No.20031019）.
文摘The effect of penicillin on the human peripheral lymphocytes was studied by steady fluorescent technique and ratiometric fluorescence dye, Fura-2. The change of the free calcium concentration in cytosol was examined under different conditions. A characterization of Fura-2-Ca interaction in an isotonic saline solution showed that Ca2+ formed a 1*1 Fura-2-Ca complex with the apparent dissociation constant 1.81×10-7 mol/L. The mechanism, by which penicillin induced the decrease of [Ca2+]i , was discussed in detail. The low dose of penicillin might modify the lymphocytes’ immunology response by interfering the increase in the intracellular free calcium concentration.
基金Supported by the National Natural Science Foundation of China(21676272)Major Science and Technology Project of Water Pollution Control and Management in China(2017ZX07402003)the Key Research Program of the Chinese Academy of Sciences(ZDRW-ZS-2016-5-3)
文摘The extraction of penicillin G by ionic liquid[Bmim]PF_6 has exhibited promising prospect.The stability of penicillin G is crucial for developing a green ionic liquid-based extraction technology.In this work,the stability of penicillin G in[Bmim]PF_6 was systematically investigated.The results showed the stability of penicillin G was significantly influenced by pH and temperature.It tended to be more stable when pH value increased from 1.5 to 4.0 and the temperature gradually decreased.The half-life(t_(1/2))of penicillin G in[Bmim]PF_6 was 17.7 h in the optimal technological condition(pH 2.0 and 10°C),which is enough for the requirement of extraction technology.The reaction of penicillin G in[Bmim]PF_6 followed the first order kinetics in the pH range 2.0–4.0.Three isomers of penicillin G were found through rearrangement at pH 2.0,and their structures were not affected by temperature.
