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1

Synthesis and antibacterial activity of quinolone-based compounds containing a coumarin moiety.  

PubMed

A new series of quinolone-based compounds containing a coumarin moiety have been synthesized and studied for their antibacterial activity against a panel of gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The results of the antibacterial evaluation of N-[2-(coumarin-3-yl)ethyl]piperazinyl quinolone derivatives in comparison with parent quinolones (norfloxacin, ciprofloxacin, and enoxacin) indicated that N-[2-(coumarin-3-yl)-2-oxoethyl]ciprofloxacin derivative (compound 8b) showed comparable or more potent antibacterial activity with respect to the reference drugs against the test strains. Generally, in both gram-positive and gram-negative bacteria, better results are obtained with cyclopropyl at the N-1 position of the quinolone ring and 2-oxo- on the ethyl spacer of coumarin and piperazine rings. PMID:18072241

Emami, Saeed; Foroumadi, Alireza; Faramarzi, Mohammad A; Samadi, Nasrin

2008-01-01

2

Synthesis and antibacterial activity of some novel N-substituted piperazinyl-quinolones.  

PubMed

A series of N-substituted-piperazinyl-quinolones were synthesized and evaluated for in vitro antibacterial activity. Compounds with a 2-(2,4-dichlorophenyl)-2-oxoethyl group attached to the piperazine ring (5a-c) had similar antibacterial activity to the reference drugs, ciprofloxacin, norfloxacin and enoxacin against both Gram-positive and Gram-negative bacteria. The oximes 6a-c and 6g-i were almost less active than corresponding ketones against the tested microorganisms, however the 2,4-difluorophenyl analogues (6g-i) were more active than 2,4-dichlorophenyl derivatives (6a-c). If the hydrogen of oxime is replaced with a benzyl group (6d-f & 6j-l), in-vitro antibacterial activity was decreased against both Gram-positive and Gram-negative bacteria. Generally ciprofloxacin derivatives were more active than norfloxacin and enoxacin derivatives. PMID:11822230

Foroumadi, A; Davood, A; Mirzaei, M; Emami, S; Moshafi, M H

2001-01-01

3

Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives.  

PubMed

A series of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl) derivatives of piperazinyl quinolones was synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit high activity against Gram-positive bacteria; Staphylococcus aureus and Staphylococcus epidermidis, comparable or more potent than their parent N-piperazinyl quinolones norfloxacin and ciprofloxacin as reference drugs. The SAR of this series indicates that both the structure of the benzyl unit and the S or SO(2) linker dramatically impact antibacterial activity. PMID:16105736

Foroumadi, Alireza; Emami, Saeed; Hassanzadeh, Abdolreza; Rajaee, Majid; Sokhanvar, Kazem; Moshafi, Mohammad Hassan; Shafiee, Abbas

2005-10-15

4

Mechanism of quinolone action and resistance.  

PubMed

Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains. PMID:24576155

Aldred, Katie J; Kerns, Robert J; Osheroff, Neil

2014-03-18

5

Quinolones: a practical review of clinical uses, dosing considerations, and drug interactions.  

PubMed

A review of the literature on quinolones reveals numerous clinically relevant points regarding indications, dosing considerations, and drug interactions. Quinolones are useful in the treatment of several infectious diseases. Unfortunately, indiscriminate use of these valuable antimicrobials has resulted in increased patterns of resistance. It is important to consider carefully the site of infection and the potential pathogens in each patient before dosing. Quinolones have excellent oral absorption, with peak serum concentrations approaching those achieved with intravenous administration. When prescribing quinolones, the dose should be based on estimated creatinine clearance. Quinolones are associated with several clinically significant drug interactions. Some of these agents are well-documented inhibitors of hepatic metabolism of theophylline, caffeine, and warfarin. It has been well documented that divalent and trivalent cations in antacids, sucralfate, and some other products significantly reduce the absorption of quinolones. Avoidance or proper management of these interactions is required to ensure optimal safety and efficacy. PMID:8537808

Borcherding, S M; Stevens, R; Nicholas, R A; Corley, C R; Self, T

1996-01-01

6

Quinolone-3-diarylethers: a new class of antimalarial drug.  

PubMed

The goal for developing new antimalarial drugs is to find a molecule that can target multiple stages of the parasite's life cycle, thus impacting prevention, treatment, and transmission of the disease. The 4(1H)-quinolone-3-diarylethers are selective potent inhibitors of the parasite's mitochondrial cytochrome bc1 complex. These compounds are highly active against the human malaria parasites Plasmodium falciparum and Plasmodium vivax. They target both the liver and blood stages of the parasite as well as the forms that are crucial for disease transmission, that is, the gametocytes, the zygote, the ookinete, and the oocyst. Selected as a preclinical candidate, ELQ-300 has good oral bioavailability at efficacious doses in mice, is metabolically stable, and is highly active in blocking transmission in rodent models of malaria. Given its predicted low dose in patients and its predicted long half-life, ELQ-300 has potential as a new drug for the treatment, prevention, and, ultimately, eradication of human malaria. PMID:23515079

Nilsen, Aaron; LaCrue, Alexis N; White, Karen L; Forquer, Isaac P; Cross, R Matthew; Marfurt, Jutta; Mather, Michael W; Delves, Michael J; Shackleford, David M; Saenz, Fabian E; Morrisey, Joanne M; Steuten, Jessica; Mutka, Tina; Li, Yuexin; Wirjanata, Grennady; Ryan, Eileen; Duffy, Sandra; Kelly, Jane Xu; Sebayang, Boni F; Zeeman, Anne-Marie; Noviyanti, Rintis; Sinden, Robert E; Kocken, Clemens H M; Price, Ric N; Avery, Vicky M; Angulo-Barturen, Iñigo; Jiménez-Díaz, María Belén; Ferrer, Santiago; Herreros, Esperanza; Sanz, Laura M; Gamo, Francisco-Javier; Bathurst, Ian; Burrows, Jeremy N; Siegl, Peter; Guy, R Kiplin; Winter, Rolf W; Vaidya, Akhil B; Charman, Susan A; Kyle, Dennis E; Manetsch, Roman; Riscoe, Michael K

2013-03-20

7

Recent advances in antibacterial drugs  

PubMed Central

The incidence of antimicrobial resistance is on continued rise with a threat to return to the “pre-antibiotic” era. This has led to emergence of such bacterial infections which are essentially untreatable by the current armamentarium of available treatment options. Various efforts have been made to develop the newer antimicrobials with novel modes of action which can act against these multi-drug resistant strains. This review aims to focus on these newly available and investigational antibacterials approved after year 2000, their mechanism of actions/resistance, and spectrum of activity and their phases of clinical trials. Newer unexploited targets and strategies for the next generation of antimicrobial drugs for combating the drug resistance and emerging pathogens in the 21st century have also been reviewed in the present article. PMID:23776832

Rai, Jaswant; Randhawa, Gurpreet Kaur; Kaur, Mandeep

2013-01-01

8

Synthesis and in vitro antibacterial activity of some N-(5-aryl-1,3,4-thiadiazole-2-yl)piperazinyl quinolone derivatives.  

PubMed

A series of N-[5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole-2-yl] and N-[5-(nitrophenyl)-1,3,4-thiadiazole-2-yl] piperazinyl quinolone derivatives (5a-c and 5d-l) were synthesized and evaluated for in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria. The antibacterial data revealed that all nitroimidazole derivatives (5a-c) showed interesting activity against tested Gram-positive bacteria (minimum inhibitory concentration, MIC=0.008-0.03 microg/ml) while they did not show good activity against Gram-negative organisms. Despite the significant activity of nitroimidazole series, all nitrophenyl analogues (5d-l) were inactive against both Gram-positive and Gram-negative bacteria. Among all of the tested compounds, 5a (ciprofloxacin derivative in nitroimidazole series) exhibited excellent activity against Staphylococcus aureus and Staphylococcus epidermidis (MIC=0.008 microg/ml). PMID:14505733

Foroumadi, Alireza; Soltani, Fatemeh; Moshafi, Mohammad Hasan; Ashraf-Askari, Rogheeyeh

2003-10-01

9

Antibacterial drug leads targeting isoprenoid biosynthesis.  

PubMed

With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)(90) ?0.25 µg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies. PMID:23248302

Zhu, Wei; Zhang, Yonghui; Sinko, William; Hensler, Mary E; Olson, Joshua; Molohon, Katie J; Lindert, Steffen; Cao, Rong; Li, Kai; Wang, Ke; Wang, Yang; Liu, Yi-Liang; Sankovsky, Anna; de Oliveira, César Augusto F; Mitchell, Douglas A; Nizet, Victor; McCammon, J Andrew; Oldfield, Eric

2013-01-01

10

UV-Vis spectrophotometrical and analytical methodology for the determination of singlet oxygen in new antibacterials drugs.  

PubMed

We have determined and quantified spectrophotometrically the capacity of producing reactive oxygen species (ROS) as (1)O(2) during the photolysis with UV-A light of 5 new synthesized naphthyl ester derivates of well-known quinolone antibacterials (nalidixic acid (1), cinoxacin (2), norfloxacin (3), ciprofloxacin (4) and enoxacin (5)). The ability of the naphthyl ester derivatives (6-10) to generate singlet oxygen were detecting and for the first time quantified by the histidine assay, a sensitive, fast and inexpensive method. The following tendency of generation of singlet oxygen was observed: compounds 7 > 10 > 6 > 8 > 9 > parent drugs 1-5. PMID:19662185

Zoltan, Tamara; Vargas, Franklin; Izzo, Carla

2007-01-01

11

Quinolone-3-Diarylethers: A new class of drugs for a new era of malaria eradication  

PubMed Central

Ideally antimalarial drugs can be developed which target multiple life cycle stages, thus impacting prevention, treatment and transmission of disease. Here we introduce 4-(1H)-quinolone-3-diarylethers that are selectively potent inhibitors of the parasite’s mitochondrial cytochrome bc1 complex. These compounds are highly active against the primary human malarias (falciparum and vivax), targeting the parasite at both the liver and blood stages as well as the forms that are crucial to disease transmission: gametocytes ? zygotes ? ookinetes ? oocysts. Chosen as the preclinical candidate, ELQ-300 has good oral bioavailability at efficacious dosages in mice, is metabolically stable, and is highly active in rodent malaria models. Given a low predicted dose in patients and a long predicted half-life, ELQ-300 offers the hope of a new molecule for the treatment, prevention and, ultimately, eradication of malaria. PMID:23515079

White, Karen L.; Forquer, Isaac P.; Cross, Richard M.; Marfurt, Jutta; Mather, Michael W.; Delves, Michael J.; Shackleford, David M.; Saenz, Fabian E.; Morrisey, Joanne M.; Steuten, Jessica; Mutka, Tina; Li, Yuexin; Wirjanata, Grennady; Ryan, Eileen; Duffy, Sandra; Kelly, Jane Xu; Sebayang, Boni F.; Zeeman, Anne-Marie; Noviyanti, Rintis; Sinden, Robert E.; Kocken, Clemens H. M.; Price, Ric N.; Avery, Vicky M.; Angulo-Barturen, Inigo; Jimenez-Diaz, Maria Belen; Ferrer, Santiago; Herreros, Esperanza; Sanz, Laura M.; Gamo, Francisco-Javier; Bathurst, Ian; Burrows, Jeremy N.; Siegl, Peter; Guy, R. Kiplin; Winter, Rolf W.; Vaidya, Akhil B.; Charman, Susan A.; Kyle, Dennis E.; Manetsch, Roman; Riscoe, Michael K.

2014-01-01

12

Synthesis and antibacterial activity of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[(2-5-bromothiophen-2-yl)-2-oximinoethyl] derivatives of piperazinyl quinolones.  

PubMed

A series of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[2-(5-bromothiophen-2-yl)-2-oximinoethyl]derivatives of piperazinyl quinolones were synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit comparable or better activity against Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis, than ciprofloxacin, norfloxacin and enoxacine as reference drugs. PMID:16115766

Foroumadi, Alireza; Emami, Saeed; Mehni, Massood; Moshafi, Mohammad Hassan; Shafiee, Abbas

2005-10-15

13

[Choice of antibacterial drugs in urinary infection].  

PubMed

A rise in efficacy of the treatment of acute infection affecting the lower urinary tract (LUTI) and prolongation of recurrence-free interval in chronic LUTI can be achieved only by an optimal antibacterial treatment. The study was made of 987 community-acquired strains of uropathogens from the patients living in 20 cities of the Russian Federation, Belarus and Kazakhstan (of them, 903 strains were from Russia). Enterobacteriaceae comprised 83.5%. E. coli infection of LUTI was found in 63.5% patients. The incidence of this infection was about the same both in uncomplicated and complicated cases (64.6 and 62.1%, respectively). Most active oral drugs against E.coli were phosphomycin (98.4%), furasidin (95.7%), nitrofurantoin (94.1%) and oralcefalosporins of the third generation (ceftibuten and cefixim). As to Enterobacteriaceae, only phosphomycin had activity against these bacteria above 90%, i.e. 91.5%. Furasidin and nitrofurantoin activity was 86.3 and 76.8%, respectively. From parenteral drugs, most active against E. coli were carbapenems (ertapenem, meropenem, imipenem. Strains resistant to them were not isolated. High in vitro activity was demonstrated also by cefoperason/sulbactam (97.4%), piperacillin/tasobactam (95.7%), cefalosporins of the third/fourth generation and amikacin (98.9%). Carbapenems were also highly active against Enterobacteroaceae. Empiric treatment of uncomplicated urinary infection should be performed with medicines which are not used for other indications. PMID:22876623

Perepanova, T S; Kozlov, R S; Dekhnich, A V; Palagin, I S; Shevelev, A N; Volkova, E M; Égamberdiev, D K

2012-01-01

14

The antibacterial paradox: essential drugs, effectiveness, and cost.  

PubMed Central

The concept proposed by WHO of an essential drugs list that should comprise drugs corresponding to the health needs of the majority of the people has been embraced by countries, which have adapted it to their needs. In this study, the essential antibacterial drug lists of 16 countries chosen from the six WHO regions are reviewed. Most of these countries include 73% of WHO-recommended essential antibacterials on their lists. However, most are lacking reserve antibacterials, and even some main list antibacterials, which are essential when empirical therapy fails in cases of bacterial resistance. Many factors that may be responsible for the lack of selection of these drugs, not least cost considerations, are discussed. PMID:10212510

Fasehun, F.

1999-01-01

15

Comparison of the antibacterial activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin  

Microsoft Academic Search

The in-vitro activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin were compared. Gram-positive cocci were most susceptible to Bay 12-8039, clinafloxacin and trovafloxacin; Enterobacteriaceae and fas- tidious organisms were most susceptible to ciprofloxacin ; Pseudomonas spp. were most susceptible to clinafloxacin and ciprofloxacin; anaerobes, Helicobacter pylori and Campylo - bacter jejuni were most susceptible

A. Bauernfeind

1997-01-01

16

Functional Analysis of Pneumococcal Drug Efflux Pumps Associates the MATE DinF Transporter with Quinolone Susceptibility  

PubMed Central

The pneumococcal chromosome encodes about 140 transporters, many of which are predicted to be involved in efflux. In order to critically evaluate pneumococcal efflux, a series of transporter mutants were constructed, and their phenotypes were assayed by disk diffusion, microdilution drug susceptibility testing (MIC testing), growth of cultures at sub-MIC concentrations, and phenotype microarray analysis. Mutants with mutations in seven ATP binding cassette (ABC) transporters, three multiantimicrobial extrusion (MATE) family efflux pumps, and one major facilitator superfamily (MFS) transporter were obtained in Streptococcus pneumoniae strain DP1004. The susceptibility of these 11 mutants to over 250 different substances was compared to that of the parent strain. Of the tested transporters, only the ABC transporter PatAB (SP2073-5) presented a clear multidrug resistance (MDR) profile, as the mutant showed significantly increased susceptibility to ethidium bromide, acriflavine, and berberine. Among the other transporters analyzed, the mutants devoid of the MATE efflux pump SP2065 exhibited reduced susceptibility to novobiocin, and those with mutations of the MATE family DinF transport system (SP1939) exhibited increased susceptibility to moxifloxacin, ciprofloxacin, and levofloxacin. This change in quinolone MIC was found to be independent from the competence-mediated effect of quinolones on the cinA-recA-dinF operon. Furthermore, the dinF mutant, in contrast to the parental strain, allowed selection for quinolone-resistant mutants when exposed to moxifloxacin. These data confirm the clear MDR profile of the PatAB ABC transporter and suggest for the MATE DinF a phenotype associated with quinolone susceptibility, particularly for moxifloxacin. PMID:23114782

Tocci, Nadia; Iannelli, Francesco; Bidossi, Alessandro; Ciusa, Maria Laura; Decorosi, Francesca; Viti, Carlo; Pozzi, Gianni; Ricci, Susanna

2013-01-01

17

THE EFFECT OF ANTIBACTERIAL DRUGS ON THE WEIGHT OF MICE  

PubMed Central

NCS mice gained weight rapidly when fed a gluten diet deficient in several amino acids, but their weight gain on the same regimen was very much retarded if they were given antibacterial drugs, even for a short period of time. This retardation of growth could not be entirely corrected by supplementing the gluten diet with lysine and threonine. The decrease in growth rate brought about by antibacterial drugs could probably be traced to the alteration in intestinal flora resulting from drug treatment. The intensity and duration of both types of changes were related to the dose of drug administered, and to the length of the treatment period. Whatever the nutritional regimen, treatment with penicillin caused a retardation of weight gain in NCS mice. The retardation was more pronounced, and longer lasting, when the animals were fed semisynthetic regimens (containing casein or gluten) than when they were fed crude diets (pellets) containing natural materials of ill defined composition. These differences probably had their origin in the fact that the changes in fecal flora induced by the drugs were profoundly influenced by the composition of the diet. Antibacterial drugs which retarded weight gain of Swiss NCS mice, in contrast increased weight gain in ordinary Swiss mice raised under usual conditions. It is probable that this difference in response to the antibacterial drugs resulted from the fact that ordinary Swiss mice have a much more complex intestinal flora than NCS animals. PMID:19867224

Dubos, Rene; Schaedler, Russell W.; Costello, Richard L.

1963-01-01

18

Quinolones: review of psychiatric and neurological adverse reactions.  

PubMed

Quinolones are a class of antibacterial agents for the treatment of several infectious diseases (e.g. urinary and respiratory tract infections). They are used worldwide due to their broad spectrum of activity, high bioavailability and good safety profile. The safety profile varies from quinolone to quinolone. The aim of this article was to review the neurological and psychiatric adverse drug reaction (ADR) profile of quinolones, using a literature search strategy designed to identify case reports and case series. A literature search using PubMed/MEDLINE (from inception to 31 October 2010) was performed to identify case reports and case series related to quinolone-associated neurological and psychiatric ADRs. The search was conducted in two phases: the first phase was the literature search and in the second phase relevant articles were identified through review of the references of the selected articles. Relevant articles were defined as articles referring to adverse events/reactions associated with the use of any quinolone. Abstracts referring to animal studies, clinical trials and observational studies were excluded. Identified case reports were analysed by age group, sex, active substances, dosage, concomitant medication, ambulatory or hospital-based event and seriousness, after Medical Dictionary for Regulatory Activities (MedDRA®) coding. From a total of 828 articles, 83 were identified as referring to nervous system and/or psychiatric disorders induced by quinolones. 145 individual case reports were extracted from the 83 articles. 40.7% of the individual case reports belonged to psychiatric disorders only, whereas 46.9% related to neurological disorders only. Eight (5.5%) individual case reports presented both neurological and psychiatric ADRs. Ciprofloxacin, ofloxacin and pefloxacin were the quinolones with more neurological and psychiatric ADRs reported in the literature. Ciprofloxacin has been extensively used worldwide, which may explain the higher number of reports, while for ofloxacin and pefloxacin, the number of reports may be over-representative. A total of 232 ADRs were identified from the selected articles, with 206 of these related to psychiatric and/or neurological ADRs. The other 26 were related to other body systems but were reported together with the reactions of interest. Mania, insomnia, acute psychosis and delirium were the most frequently reported psychiatric adverse events; grand mal convulsion, confusional state, convulsions and myoclonus were the most frequently reported neurological adverse events. Several aspects should be taken into account in the development of CNS adverse effects, such as the pharmacokinetics of quinolones, chemical structure and quinolone uptake in the brain. These events may affect not only susceptible patients but also 'healthy' patients. PMID:21585220

Tomé, Ana M; Filipe, Augusto

2011-06-01

19

Evaluating polymer monolith in-tube solid-phase microextraction coupled to liquid chromatography/quadrupole time-of-flight mass spectrometry for reliable quantification and confirmation of quinolone antibacterials in edible animal food.  

PubMed

A simple, rapid, and sensitive method is presented to determine seven trace quinolone antibacterials simultaneously in milk, egg, chicken and fish. This method is based on the combination of polymer monolith in-tube solid-phase microextraction with liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI-QTOF-MS). LC/ESI-QTOF-MS offers the capability of unequivocal identification of target compounds from complex matrices, as well as the possibility of quantitation at low-level concentrations in real samples. The extraction was performed with a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic column. Under the optimized extraction conditions, good extraction efficiencies for the targets were obtained with no matrix interference in the subsequent LC/ESI-QTOF-MS. Good linearities were obtained for seven quinolones with the correlation coefficients (R) above 0.9951. The limits of detection (S/N=3) for seven quinolones were found to be 0.3-1.2 ng/g in egg, 0.2-3.0 ng/mL in milk, 0.2-0.7 ng/g in chicken and 0.2-1.0 ng/g in fish. The recoveries of quinolones spiked in four different matrices ranged from 80.2 to 115.0%, with relative standard deviations less than 14.5%. The developed method was applied for the determination of quinolone residues in animal-producing food, and the positive samples were confirmed with high number of identification points (IPs) according to the IP system defined by the European Union (Commission Decision 2002/657/EC). PMID:19345953

Zheng, Ming-Ming; Ruan, Ge-Deng; Feng, Yu-Qi

2009-10-30

20

The evolving role of chemical synthesis in antibacterial drug discovery.  

PubMed

The discovery and implementation of antibiotics in the early twentieth century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within pathogenic bacteria, made worse by widespread misuse of antibiotics. For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but economic factors have led to a subsidence of this effort, which places society on the precipice of a disaster. We believe that the strategic application of modern chemical synthesis to antibacterial drug discovery must play a critical role if a crisis of global proportions is to be averted. PMID:24990531

Wright, Peter M; Seiple, Ian B; Myers, Andrew G

2014-08-18

21

The evolutionary rate of antibacterial drug targets  

PubMed Central

Background One of the major issues in the fight against infectious diseases is the notable increase in multiple drug resistance in pathogenic species. For that reason, newly acquired high-throughput data on virulent microbial agents attract the attention of many researchers seeking potential new drug targets. Many approaches have been used to evaluate proteins from infectious pathogens, including, but not limited to, similarity analysis, reverse docking, statistical 3D structure analysis, machine learning, topological properties of interaction networks or a combination of the aforementioned methods. From a biological perspective, most essential proteins (knockout lethal for bacteria) or highly conserved proteins (broad spectrum activity) are potential drug targets. Ribosomal proteins comprise such an example. Many of them are well-known drug targets in bacteria. It is intuitive that we should learn from nature how to design good drugs. Firstly, known antibiotics are mainly originating from natural products of microorganisms targeting other microorganisms. Secondly, paleontological data suggests that antibiotics have been used by microorganisms for million years. Thus, we have hypothesized that good drug targets are evolutionary constrained and are subject of evolutionary selection. This means that mutations in such proteins are deleterious and removed by selection, which makes them less susceptible to random development of resistance. Analysis of the speed of evolution seems to be good approach to test this hypothesis. Results In this study we show that pN/pS ratio of genes coding for known drug targets is significantly lower than the genome average and also lower than that for essential genes identified by experimental methods. Similar results are observed in the case of dN/dS analysis. Both analyzes suggest that drug targets tend to evolve slowly and that the rate of evolution is a better predictor of drugability than essentiality. Conclusions Evolutionary rate can be used to score and find potential drug targets. The results presented here may become a useful addition to a repertoire of drug target prediction methods. As a proof of concept, we analyzed GO enrichment among the slowest evolving genes. These may become the starting point in the search for antibiotics with a novel mechanism. PMID:23374913

2013-01-01

22

Bacillus anthracis GrlAV96A Topoisomerase IV, a Quinolone Resistance Mutation That Does Not Affect the Water-Metal Ion Bridge.  

PubMed

The rise in quinolone resistance is threatening the clinical use of this important class of broad-spectrum antibacterials. Quinolones kill bacteria by increasing the level of DNA strand breaks generated by the type II topoisomerases gyrase and topoisomerase IV. Most commonly, resistance is caused by mutations in the serine and acidic amino acid residues that anchor a water-metal ion bridge that facilitates quinolone-enzyme interactions. Although other mutations in gyrase and topoisomerase IV have been reported in quinolone-resistant strains, little is known regarding their contributions to cellular quinolone resistance. To address this issue, we characterized the effects of the V96A mutation in the A subunit of Bacillus anthracis topoisomerase IV on quinolone activity. The results indicate that this mutation causes an ?3-fold decrease in quinolone potency and reduces the stability of covalent topoisomerase IV-cleaved DNA complexes. However, based on metal ion usage, the V96A mutation does not disrupt the function of the water-metal ion bridge. A similar level of resistance to quinazolinediones (which do not use the bridge) was seen. V96A is the first topoisomerase IV mutation distal to the water-metal ion bridge demonstrated to decrease quinolone activity. It also represents the first A subunit mutation reported to cause resistance to quinazolinediones. This cross-resistance suggests that the V96A change has a global effect on the structure of the drug-binding pocket of topoisomerase IV. PMID:25246407

Aldred, Katie J; Breland, Erin J; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

2014-12-01

23

Undecaprenyl diphosphate synthase inhibitors: antibacterial drug leads.  

PubMed

There is a significant need for new antibiotics due to the rise in drug resistance. Drugs such as methicillin and vancomycin target bacterial cell wall biosynthesis, but methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) have now arisen and are of major concern. Inhibitors acting on new targets in cell wall biosynthesis are thus of particular interest since they might also restore sensitivity to existing drugs, and the cis-prenyl transferase undecaprenyl diphosphate synthase (UPPS), essential for lipid I, lipid II, and thus, peptidoglycan biosynthesis, is one such target. We used 12 UPPS crystal structures to validate virtual screening models and then assayed 100 virtual hits (from 450,000 compounds) against UPPS from S. aureus and Escherichia coli. The most promising inhibitors (IC50 ?2 ?M, Ki ?300 nM) had activity against MRSA, Listeria monocytogenes, Bacillus anthracis, and a vancomycin-resistant Enterococcus sp. with MIC or IC50 values in the 0.25-4 ?g/mL range. Moreover, one compound (1), a rhodanine with close structural similarity to the commercial diabetes drug epalrestat, exhibited good activity as well as a fractional inhibitory concentration index (FICI) of 0.1 with methicillin against the community-acquired MRSA USA300 strain, indicating strong synergism. PMID:24827744

Sinko, William; Wang, Yang; Zhu, Wei; Zhang, Yonghui; Feixas, Ferran; Cox, Courtney L; Mitchell, Douglas A; Oldfield, Eric; McCammon, J Andrew

2014-07-10

24

Preparation, structure and microbial evaluation of metal complexes of the second generation quinolone antibacterial drug lomefloxacin  

NASA Astrophysics Data System (ADS)

Lomefloxacinate of Y(III), Zr(IV) and U(VI) were isolated as solids with the general formula; [Y(LFX) 2Cl 2]Cl·12H 2O, [ZrO(LFX) 2Cl]Cl·15H 2O and [UO 2(LFX) 3](NO 3) 2·4H 2O. The new synthesized complexes were characterized with physicochemical and diverse spectroscopic techniques (IR, UV-Vis. and 1H NMR spectroscopies) as well as thermal analyses. In these complexes lomefloxacin act as bidentate ligand bound to the metal ions through the pyridone oxygen and one carboxylate oxygen. The kinetic parameters of thermogravimetric (TGA) and its differential (DTG), such as entropy of activation, activation energy, enthalpy of activation and Gibbs free energy evaluated by using Coats- Redfern and Horowitz- Metzger equations for free lomefloxacin and three complexes were carried out. The bond stretching force constant and length of the U dbnd O bond for the [UO 2(LFX) 3](NO 3) 2·4H 2O complex were calculated. The antimicrobial activity of lomefloxacin and its metal complexes was tested against different bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) as Gram-positive and Gram-negative bacterial species and also against two species of antifungal, penicillium ( P. rotatum) and trichoderma ( T. sp.). The three complexes are of a good action against three bacterial species but the Y(III) complex exhibit excellent activity against Pseudomonas aeruginosa ( P. aeruginosa), when compared to the free lomefloxacin.

Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

2010-09-01

25

Metal complexes of the fourth generation quinolone antimicrobial drug gatifloxacin: Synthesis, structure and biological evaluation  

NASA Astrophysics Data System (ADS)

Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(???), Zr(?V) and U(V?) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, gatifloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylato oxygen. The complexes are six-coordinated with distorted octahedral geometry. The kinetic parameters for gatifloxacin and the three prepared complexes have been evaluated from TGA curves by using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The calculated bond length and force constant, F(U dbnd O), for the UO 2 bond in uranyl complex are 1.7522 Å and 639.46 N m -1. The antimicrobial activity of the complexes has been tested against microorganisms, three bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) and two fungi species, penicillium ( P. rotatum) and trichoderma ( T. sp.), showing that they exhibit higher activity than free ligand.

Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

2010-08-01

26

Newer Antibacterials in Therapy and Clinical Trials  

PubMed Central

In order to deal with the rising problem of antibiotic resistance, newer antibacterials are being discovered and added to existing pool. Since the year 2000, however, only four new classes of antibacterials have been discovered. These include the oxazolidinones, glycolipopeptides, glycolipodepepsipeptide and pleuromutilins. Newer drugs were added to existing classes of antibiotics, such as streptogramins, quinolones, beta-lactam antibiotics, and macrolide-, tetracycline- and trimethoprim-related drugs. Most of the antibacterials are directed against resistant S. aureus infections, with very few against resistant gram-negative infections. The following article reviews the antibacterials approved by the FDA after the year 2000 as well as some of those in clinical trials. Data was obtained through a literature search via Pubmed and google as well as a detailed search of our library database. PMID:23181224

Paknikar, Simi S; Narayana, Sarala

2012-01-01

27

Quinolones in Salmonella typhi infection.  

PubMed

The quinolones possess a high degree of in vitro activity against enteric bacteria, including Salmonella. This observation, coupled with the limitations of current antityphoid agents, has resulted in the evaluation of quinolones in the therapy of S. typhi infection, including both enteric fever and chronic intestinal carriage. In open uncontrolled trials, norfloxacin, ciprofloxacin, ofloxacin and pefloxacin have been used successfully to treat more than 200 patients with culture-proven typhoid fever. In comparative clinical trials, ciprofloxacin, ofloxacin, pefloxacin or fleroxacin were equivalent or superior to standard antityphoid therapy. In separate studies, norfloxacin and ciprofloxacin were each effective in eliminating intestinal excretion of S. typhi in chronic carriers. Because of increasing resistance worldwide to conventional antityphoid drugs, and in view of the efficacy of the quinolones in the therapy of both typhoid fever and typhoid intestinal carriage, these drugs may become the treatment of choice for these important enteric infections. PMID:7689442

DuPont, H L

1993-01-01

28

The anti-inflammatory non-antibiotic helper compound diclofenac: an antibacterial drug target  

Microsoft Academic Search

Diclofenac sodium (Dc) was found to possess antibacterial activity against both drug-sensitive and drug-resistant clinical\\u000a isolates of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to its potent anti-inflammatory activity. The time-kill curve study indicates that this non-steroidal drug\\u000a exhibits bactericidal activity against Listeria, E. coli, and M. tuberculosis. The antibacterial activity of Dc comes, in part,

K. Mazumdar; S. G. Dastidar; J. H. Park; N. K. Dutta

2009-01-01

29

DRUG DISCOVERY AND RESISTANCE Antibacterial activities of dendritic amphiphiles against nontuberculous  

E-print Network

DRUG DISCOVERY AND RESISTANCE Antibacterial activities of dendritic amphiphiles against November 2011 Accepted 4 December 2011 Keywords: Dendritic amphiphiles Nontuberculous mycobacteria Anti of nine series of dicarboxyl and tricarboxyl dendritic amphiphiles with one alkyl, two alkyl

Falkinham, Joseph

30

FROM THE ANALYST'S COUCH The antibacterial drugs market  

E-print Network

, the development of antibacterials has become increasingly unattractive to big pharma for a number of reasons/or by picking up clinical programmes aborted by the larger companies. However, big pharma often becomes involved pharma markets (which has been primarily driven by price increases) has slowed to a compound annual

Cai, Long

31

Antiplasmodial Drugs in the Gas Phase: A CID and DFT Study of Quinolon-4( 1H)-Imine Derivatives  

NASA Astrophysics Data System (ADS)

The gas-phase behavior of 12 quinolon-4( 1H)-imine derivatives with antiplasmodial activity was investigated using electrospray ionization tandem mass spectrometry together with collision induced dissociation and density functional theory (DFT) calculations. The most probable protonation site was predicted by calculating the proton affinity (PA) values for each possible protonation site and it was found to be the imine nitrogen for all compounds under study. Fragmentation pathways of the protonated molecules were proposed and the assignment of product ion structures was performed taking into account theoretical calculations. The nature of the quinoline substituent was found to influence the gas-phase behavior of the compounds under study. The data acquired allowed to bracket the proton affinity of the quinolin-4-imine scaffold, which can be a useful starting point to choose appropriate references for determining PA values of this scaffold.

Amorim Madeira, Paulo J.; Sitoe, Ana Raquel Fernandes; Gonçalves, Daniel; Rodrigues, Tiago; Guedes, Rita C.; Lopes, Francisca; Moreira, Rui; Bronze, M. Rosário

2014-09-01

32

Synthesis, characterization, antibacterial activity, SOD mimic and interaction with DNA of drug based copper(II) complexes  

NASA Astrophysics Data System (ADS)

Novel metal complexes of the second-generation quinolone antibacterial agent enrofloxacin with copper(II) and neutral bidentate ligands have been prepared and characterized with elemental analysis reflectance, IR and mass spectroscopy. Complexes have been screened for their in-vitro antibacterial activity against two Gram (+ve)Staphylococcus aureus, Bacillus subtilis, and three Gram (-ve)Serratia marcescens, Escherichia coli and Pseudomonas aeruginosa organisms using the double dilution technique. The binding of this complex with CT-DNA has been investigated by absorption titration, salt effect and viscosity measurements. Binding constant is ranging from 1.3 × 10 4-3.7 × 10 4. The cleavage ability of complexes has been assessed by gel electrophoresis using pUC19 DNA. The catalytic activity of the copper(II) complexes towards the superoxide anion (O 2rad -) dismutation was assayed by their ability to inhibit the reduction of nitroblue tetrazolium (NBT).

Patel, Mohan N.; Dosi, Promise A.; Bhatt, Bhupesh S.; Thakkar, Vasudev R.

2011-02-01

33

DNA gyrase and topoisomerase IV mutations in quinolone-resistant Flavobacterium psychrophilum isolated from diseased salmonids in Norway.  

PubMed

Flavobacterium psychrophilum is the causative agent of the recognized diseases 'bacterial coldwater disease' and 'rainbow trout fry syndrome' and is found in many farmed freshwater and marine fish species. In Norway, the bacterium has mainly been isolated from Atlantic salmon (Salmo salar L.) and brown trout (Salmo trutta L.). In the present study, 26 isolates from Norwegian farmed salmonids were examined. All isolates were tested for susceptibility towards various antibacterial drugs by the disk diffusion method, and minimum inhibitory concentration values for oxolinic acid and flumequine were established for selected isolates. All isolates from rainbow trout displayed reduced susceptibility towards quinolones, while brown trout and Atlantic salmon isolates were susceptible. The quinolone resistance determining regions (QRDRs) of the gyrA, gyrB, parC, and parE genes were sequenced. Sequence analysis of the QRDR of gyrA in quinolone resistant isolates revealed a threonine:arginine amino acid substitution at position 82 in all 16 isolates from Norwegian rainbow trout and a single reference strain isolated from rainbow trout in Sweden. No evidence for plasmid-mediated quinolone resistance was found in any of the isolates. Pulsed-field gel electrophoresis and phylogenetic analysis of parC and gyrB sequences indicate a clonal relationship between rainbow trout isolates. PMID:22283604

Shah, Syed Q A; Nilsen, Hanne; Bottolfsen, Kirsten; Colquhoun, Duncan J; Sørum, Henning

2012-04-01

34

Communications: Bioencapsulation of the Antibacterial Drug Sarafloxacin in Nauplii of the Brine Shrimp Artemia franciscana  

Microsoft Academic Search

Nauplii of the brine shrimp Artemia franciscana were enriched with the antibacterial drug sarafloxacin hydrochloride to determine if levels effective against four pathogenic strains of Vibrio spp. would accumulate in brine shrimp. Three vibrio strains were Vibrio anguillarum; the fourth was V. vulnifcus. Concentrations of sarafloxacin ranging from 1 to 40% (weight volume) were incorporated into the oil phase of

B. A. Dixon; S. O. Van Poucke; M. Chair; M. Dehasque; H. J. Nelis; P. Sorgeloos; A. P. De Leenheer

1995-01-01

35

DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.  

PubMed

Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III ? subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase ? subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp. PMID:24631121

Yin, Zhou; Wang, Yao; Whittell, Louise R; Jergic, Slobodan; Liu, Michael; Harry, Elizabeth; Dixon, Nicholas E; Kelso, Michael J; Beck, Jennifer L; Oakley, Aaron J

2014-04-24

36

Design, synthesis, and antibacterial activity of demethylvancomycin analogues against drug-resistant bacteria.  

PubMed

Five novel N-substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure-based approach. The in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), gentamicin-resistant Enterococcus faecalis (GRE), methicillin-resistant Streptococcus pneumoniae (MRS), and vancomycin-resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N-(6-phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ~18-fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half-life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation. PMID:23576378

Chang, Jun; Zhang, Si-Ji; Jiang, Yong-Wei; Xu, Liang; Yu, Jian-Ming; Zhou, Wen-Jiang; Sun, Xun

2013-06-01

37

In vitro activities of new quinolones against Helicobacter pylori.  

PubMed Central

Compounds belonging to a new class of quinolones in which the fundamental C-6 fluorine atom was replaced were evaluated for in vitro antibacterial activity against 32 Helicobacter pylori strains. Since these substitutions resulted in higher inhibitory activities, these new desfluoroquinolones may be useful in eradicating H. pylori infections. PMID:9420062

Carbone, M; Fera, M T; Cecchetti, V; Tabarrini, O; Losi, E; Cusumano, V; Teti, G

1997-01-01

38

Antibacterial drugs as corrosion inhibitors for bronze surfaces in acidic solutions  

NASA Astrophysics Data System (ADS)

The present study is aiming to investigate the effect of four antibiotics (amoxicillin, ciprofloxacin, doxycycline and streptomycin,) belonging to different classes of antibacterial drugs on bronze corrosion in a solution simulating an acid rain (pH 4). Due to their ability to form protective films on the metal surface, the tested antibiotics act as corrosion inhibitors for bronze. The antibiotics were tested at various concentrations in order to determine the optimal concentration range for the best corrosion inhibiting effect. In evaluating the inhibition efficiency, polarization curves, electrochemical impedance spectroscopy, SEM and XPS measurements were used. Moreover, a correlation between the inhibition efficiency of some antibacterial drugs and certain molecular parameters was determined by quantum chemical computations. Parameters like energies EHOMO and ELUMO and HOMO-LUMO energy gap were used for correlation with the corrosion data.

Rotaru, Ileana; Varvara, Simona; Gaina, Luiza; Muresan, Liana Maria

2014-12-01

39

Nanosilver-based antibacterial drugs and devices: mechanisms, methodological drawbacks, and guidelines.  

PubMed

Despite the current advancement in drug discovery and pharmaceutical biotechnology, infection diseases induced by bacteria continue to be one of the greatest health problems worldwide, afflicting millions of people annually. Almost all microorganisms have, in fact, an intrinsic outstanding ability to flout many therapeutic interventions, thanks to their fast and easy-to-occur evolutionary genetic mechanisms. At the same time, big pharmaceutical companies are losing interest in new antibiotics development, shifting their capital investments in much more profitable research and development fields. New smart solutions are, thus, required to overcome such concerns, and should combine the feasibility of industrial production processes with cheapness and effectiveness. In this framework, nanotechnology-based solutions, and in particular silver nanoparticles (AgNPs), have recently emerged as promising candidates in the market as new antibacterial agents. AgNPs display, in fact, enhanced broad-range antibacterial/antiviral properties, and their synthesis procedures are quite cost effective. However, despite their increasing impact on the market, many relevant issues are still open. These include the molecular mechanisms governing the AgNPs-bacteria interactions, the physico-chemical parameters underlying their toxicity to prokaryotes, the lack of standardized methods and materials, and the uncertainty in the definition of general strategies to develop smart antibacterial drugs and devices based on nanosilver. In this review, we analyze the experimental data on the bactericidal effects of AgNPs, discussing the complex scenario and presenting the potential drawbacks and limitations in the techniques and methods employed. Moreover, after analyzing in depth the main mechanisms involved, we provide some general strategies/procedures to perform antibacterial tests of AgNPs, and propose some general guidelines for the design of antibacterial nanosystems and devices based on silver/nanosilver. PMID:24292075

Rizzello, Loris; Pompa, Pier Paolo

2014-03-01

40

Conformationally constrained analogs of N-substituted piperazinylquinolones: synthesis and antibacterial activity of N-(2,3-dihydro-4-hydroxyimino-4H-1-benzopyran-3-yl)-piperazinylquinolones.  

PubMed

A series of novel quinolone agents bearing a particular bulky and conformationally constrained bicyclic substituent (2,3-dihydro-4-hydroxyimino-4H-1-benzopyran-3-yl- moiety) on the piperazine ring of 7-piperazinyl quinolones (norfloxacin, enoxacin, ciprofloxacin, and levofloxacin) were synthesized and evaluated against a panel of Gram-positive and Gram-negative bacteria. Among these derivatives, ciprofloxacin counterpart 9c, highly inhibited the tested Gram-positive bacteria, superior to that of the reference drugs, and displayed antibacterial activity at non-cytotoxic concentrations. PMID:19544301

Emami, Saeed; Foroumadi, Alireza; Samadi, Nasrin; Faramarzi, Mohammad A; Rajabalian, Saeed

2009-07-01

41

Antimalarial Quinolones: Synthesis, potency, and mechanistic studies  

PubMed Central

In the present article we examine the antiplasmodial activities of novel quinolone derivatives bearing extended alkyl or alkoxy side chains terminated by a trifluoromethyl group. In the series under investigation, the IC50 values ranged from 1.2 to ? 30 nM against chloroquine-sensitive and multidrug-resistant Plasmodium falciparum strains. Modest to significant cross-resistance was noted in evaluation of these haloalkyl- and haloalkoxy-quinolones for activity against the atovaquone-resistant clinical isolate Tm90-C2B, indicating that a primary target for some of these compounds is the parasite cytochrome bc1 complex. Additional evidence to support this biochemical mechanism includes the use of oxygen biosensor plate technology to show that the quinolone derivatives block oxygen consumption by parasitized red blood cells in a fashion similar to atovaquone in side-by-side experiments. Atovaquone is extremely potent and is the only drug in clinical use that targets the Plasmodium bc1 complex, but rapid emergence of resistance to it in both mono- and combination therapy is evident and therefore additional drugs are needed to target the cytochrome bc1 complex which are active against atovaquone-resistant parasites. Our study of a number of halogenated alkyl and alkoxy 4(1H)-quinolones highlights the potential for development of “endochin-like quinolones” (ELQ) bearing an extended trifluoroalkyl moiety at the 3-position that exhibit selective antiplasmodial effects in the low nanomolar range and inhibitory activity against chloroquine and atovaquone resistant parasites. Further studies of halogenated alkyl and alkoxy quinolones may lead to the development of safe and effective therapeutics for use in treatment or prevention of malaria and other parasitic diseases. PMID:18082162

Winter, Rolf W.; Kelly, Jane X.; Smilkstein, Martin J.; Dodean, Rozalia; Hinrichs, David; Riscoe, Michael K.

2008-01-01

42

Microbial geneticsGenetic strategies for antibacterial drug discovery  

Microsoft Academic Search

The availability of genome sequences is revolutionizing the field of microbiology. Genetic methods are being modified to facilitate rapid analysis at a genome-wide level and are blossoming for human pathogens that were previously considered intractable. This revolution coincided with a growing concern about the emergence of microbial drug resistance, compelling the pharmaceutical industry to search for new antimicrobial agents. The

Jonathan Greene; Todd A. Black; Lynn Miesel

2003-01-01

43

In Vitro Antituberculosis Activities of ACH-702, a Novel Isothiazoloquinolone, against Quinolone-Susceptible and Quinolone-Resistant Isolates?  

PubMed Central

ACH-702 is a new isothiazoloquinolone with potent in vitro and in vivo activities against important bacterial pathogens, including Staphylococcus aureus. In this study, ACH-702 was found to have promising in vitro antibacterial activity against Mycobacterium tuberculosis, with MICs of ?1 ?g/ml, comparable to that of the fluoroquinolone moxifloxacin for quinolone-susceptible isolates but superior to that for quinolone-resistant isolates. Biochemical assays involving M. tuberculosis gyrase enzymes indicated that ACH-702 had significantly improved inhibitory activity compared with fluoroquinolones. PMID:20516287

Pucci, Michael J.; Ackerman, Maria; Thanassi, Jane A.; Shoen, Carolyn M.; Cynamon, Michael H.

2010-01-01

44

Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.  

PubMed

A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex. PMID:25173851

Cui, Sheng-Feng; Peng, Li-Ping; Zhang, Hui-Zhen; Rasheed, Syed; Vijaya Kumar, Kannekanti; Zhou, Cheng-He

2014-10-30

45

Nanomechanics of drug-target interactions and antibacterial resistance detection.  

PubMed

The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions. Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures. We developed a new model(1) which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (Kd) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections. PMID:24192763

Ndieyira, Joseph W; Watari, Moyu; McKendry, Rachel A

2013-01-01

46

ALTERATIONS IN THE MOUSE CECUM AND ITS FLORA PRODUCED BY ANTIBACTERIAL DRUGS  

PubMed Central

Addition of penicillin, Terramycin, or kanamycin to the drinking water of adult mice rapidly induced in them an enlargement of the cecum. In all animals, this occurred within 12 hr after the beginning of drug administration—the effect being most pronounced with penicillin. The cecums remained enlarged and generally continued to increase in size as long as the antibacterial drugs were administered. The increase in wet weight of the cecums was due primarily to an accumulation of water in the lumens during the first 24–48 hr of drug administration. At that time, there were no detectable histological changes in any case, but the bacteriological picture differed from drug to drug. The cecums were free of bacteria in animals receiving penicillin, fusiform-shaped bacteria and bacteroides were present in those receiving Terramycin, and lactobacilli and bacteroides in those receiving kanamycin. After the initial 48 hr, an abundant and complex secondary microflora developed in all treated animals, its composition being characteristic for each type of antibacterial drug. When penicillin was administered for 2 wk, the cecal weights and microbial populations did not return to normal levels for over 14 days after discontinuance of the drug. This recovery period could be shortened to 10 days by giving the mice food contaminated with cecal homogenates prepared from normal animals. A period of 7 or 8 days was required for the cecal weights and microflora to reach normal levels when the administration of penicillin lasted only 24 hr; this period could not be shortened by giving the animals contaminated food. The effects of drugs on the size and bacterial contents of the cecum have been discussed in the light of earlier findings concerning the characteristics of the huge cecums uniformly found in germfree mice. Taken together, these observations support the hypothesis that certain elements of the intestinal microflora—not yet completely identified—play an essential role in maintaining the integrity of the water-transport mechanism in the intestinal epithelium. PMID:5662019

Savage, Dwayne C.; Dubos, René

1968-01-01

47

An analysis of FDA-approved drugs for infectious disease: antibacterial agents.  

PubMed

Drugs targeting infectious diseases have greatly improved public health. A study to evaluate all US Food and Drug Administration (FDA)-approved new molecular entities (NMEs) reveals that the number of new agents targeting infectious disease peaked during the 1990s and declined rapidly thereafter. Molecules targeting bacterial pathogens represent the most common component of anti-infectives followed by antivirals and antifungals. Focusing on antibacterial agents, an increase in new NMEs predominated from the 1960s through to the 1990s, dropping sharply thereafter. Obsolescence and resistance has eliminated one-third of these drugs. Consequently, the arsenal of antibiotics peaked in 2000 and is declining. Likewise, the number of organizations awarded at least one NME for a bacterial indication has declined to a level not seen in more than a half century. PMID:25043770

Kinch, Michael S; Patridge, Eric; Plummer, Mark; Hoyer, Denton

2014-09-01

48

Clinical applications of quinolones  

Microsoft Academic Search

The quinolone antimicrobials are the class of inhibitors of bacterial topoisomerases that has been developed most fully for clinical use in human medicine. Initial members of the class had their greatest potency against Gram-negative bacteria, but newly developed members have exhibited increased potency against Gram-positive bacteria and soon agents will be available with additional activity against anaerobic bacteria, providing a

David C Hooper

1998-01-01

49

Quinolone-Containing Therapies in the Eradication of Helicobacter pylori  

PubMed Central

Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to “rescue” therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

2014-01-01

50

Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase  

Microsoft Academic Search

Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined

Jérémie Piton; Stéphanie Petrella; Marc Delarue; Gwénaëlle André-Leroux; Vincent Jarlier; Alexandra Aubry; Claudine Mayer; Hendrik W. van Veen

2010-01-01

51

The usage of veterinary antibacterial drugs for mastitis in cattle in Norway and Sweden during 1990–1997  

Microsoft Academic Search

The prescribing patterns and annual incidence of use of antibacterial drugs for the treatment of mastitis in cattle in Norway and Sweden during the period 1990–1997 were estimated from drug wholesaler statistics. Although the drugs included in this study are also used in other species and\\/or other indications, mastitis in cattle is by far the most-common indication for their use.

Kari Grave; Christina Greko; Lolita Nilsson; Kristina Odensvik; Tormod Mørk; Marit Rønning

1999-01-01

52

Novel compound with potential of an antibacterial drug targets FtsZ protein.  

PubMed

A dynamic bacterial cytoskeleton consisting of FtsZ and other proteins is a potential target for the development of antibacterial drugs. GTPase activity of FtsZ protein leads to self-assembly of the protein. The resultant circumferential dynamic Z-ring at the centre of the cell recruits other proteins during progression and completion of bacterial cell division. There are natural compounds inhibiting one or more of these steps. Such inhibition ultimately culminates in the arrest of cell division. In this issue of the Biochemical Journal, a paper by Beuria et al. highlights the importance of the dynamics of the Z-ring for cell division. The ligand-induced enhanced degree of stabilization of FtsZ protofilaments, leading to the absence of the subsequent dissociation step, would hamper the normal functioning of the Z-ring, leading to an inhibition of cell proliferation. A novel antibacterial agent, OTBA (3-{5-[4-oxo-2-thioxo-3-(3-trifluoromethylphenyl)-thiazolidin-5-ylidenemethyl]-furan-2-yl}-benzoic acid) works via this hitherto unreported pathway. It stabilizes the FtsZ polymers, suppressing the dynamics which, in turn, inhibits cell division. PMID:19740076

Dasgupta, Dipak

2009-10-01

53

Taguchi design for optimization and development of antibacterial drug-loaded PLGA nanoparticles.  

PubMed

This research report was to develop Cefixime loaded polylactide-co-glycolide (PLGA) nanoparticles using modified precipitation method. TEM analysis indicated formation of well-formed, smooth, spherical nanoparticles with no aggregates whereas XRD recommended dispersion of drug in PLGA carrier system in amorphous form. The polymer and stabilizer concentration and organic to aqueous ratio were found to be significant factors for nanoparticles and their optimization using Taguchi design (L9). The design formulations showed entrapment efficiency (EE), particle size and poly-dispersity index (PDI) ranging 68.31 ± 1.74%, 159.8-157.7 nm and 0.126-0.149, respectively indicated small and stable nanoparticles with good homogeneity and encapsulation. The design optimized formulation drug release and permeation studies demonstrated that it is four times sustained release behavior and 1.74 times better permeation than free drug. The result of microbiological assay also suggested that optimized formulation has significant antibacterial activity against intracellular multidrug resistance (MDR) of Salmonella typhi. PMID:24315945

Sonam; Chaudhary, Hema; Kumar, Vikash

2014-03-01

54

Immobilisation of an antibacterial drug to Ti6Al4V components fabricated using selective laser melting  

NASA Astrophysics Data System (ADS)

Bacterial infections from biomedical implants and surgical devices are a major problem in orthopaedic, dental and vascular surgery. Although the sources of contaminations that lead to bacterial infections are known, it is not possible to control or avoid such infections completely. In this study, an approach to immobilise Ciprofloxacin® (an antibacterial drug) to phosphonic acid based self-assembled monolayers (SAMs) adsorbed on a selectively laser melted (SLM) Ti6Al4V structure, has been presented. X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements confirmed the attachment of SAMs and the drug. Results showed that Ciprofloxacin® is highly stable under the oxidative conditions used in this study. In-vitro stability was estimated by immersing the Ciprofloxacin® immobilised substrates in 10 mM of Tris-HCl buffer (pH-7.4) for 42 days. The Tris-HCl buffer was analysed using UV-vis spectrophotometry at 7, 14, 28 and 42 day time intervals to determine the release of the immobilised drug. The drug was observed to release in a sustained manner. 50% of the drug was released after 4 weeks with approximately 40% of the drug remaining after 6 weeks. Antibacterial susceptibility tests revealed that the immobilised drug was therapeutically active upon its release. This study demonstrates the potential to use self-assembled monolayers to modify SLM fabricated surfaces with therapeutics.

Vaithilingam, Jayasheelan; Kilsby, Samuel; Goodridge, Ruth D.; Christie, Steven D. R.; Edmondson, Steve; Hague, Richard J. M.

2014-09-01

55

[Antibacterial drug resistance in Latin America: consequences for infectious disease control].  

PubMed

Antibacterial drug resistance is a particularly significant issue in Latin America. This article explores antimicrobial resistance in three classes of clinically important bacteria: gram-positive bacteria, enterobacteria, and nonfermenting gram-negative bacilli. The gram-positive bacteria frequently responsible for infections in humans are for the most part cocci: staphylococci, streptococci (including pneumococci), and enterococci, in both community and hospital settings. This situation is no different in the Region of the Americas. Among the gram-positive bacteria, the causative agents of bacteremia are most commonly strains of coagulase-negative Staphylococcus, followed by enterococci. This report explores the resistance of these species to different antimicrobial drugs, resistance mechanisms in community and hospital strains, and new drugs for treating infections caused by these bacteria. In Latin America, antimicrobial resistance in Enterococcus strains is still a minor problem compared to the situation in the United States. The strains of the genus Streptococcus isolated from respiratory infections are still sensitive to penicillin. Furthermore, the resistance of enterobacteria is extremely important in the Region, particularly because of the broad dissemination of CTX-M extended-spectrum beta-lactamases (ESBL), some of which originated in Latin America. This article analyzes the resistance of Streptococcus pneumoniae, beta-hemolytic streptococci, and viridans group streptococci. Among the nonfermenting gram-negative bacilli, while Pseudomonas aeruginosa strains remain the leading cause of bacteremia, infections caused by strains of Acinetobacter spp. have proliferated extensively in some areas. With regard to antibiotics, several options are available for treating gram-positive bacterial infections. The same cannot be said for infections caused by enterobacteria and nonfermenting gram-negative bacilli, where options for the effective treatment of patients are still insufficient. PMID:22358396

Casellas, José María

2011-12-01

56

1. (a) Why are DNA-targeted drugs largely used as anticancer agents and not as, say, antibacterial or antifungal agents?  

E-print Network

CHEM 4170 Homework 4 1. (a) Why are DNA-targeted drugs largely used as anticancer agents and not as, say, antibacterial or antifungal agents? (b) Provide an explanation for how anticancer drugs can-damaging drugs mentioned in Question 1). (b) However, some medicinal chemists believe that these compounds

Gates, Kent. S.

57

[Antibacterial activity for clinical isolates from pediatric patients of clavulanic acid/amoxicillin (1: 14) -outcomes of special drug use investigation on antibacterial activity (annual changes)].  

PubMed

As a special drug use investigation, we monitored and assessed trends in antibacterial activity of clavulanic acid/amoxicillin (1:14) (hereafter, "CVA/AMPC (1:14)") and other antimicrobial agents for clinical isolates from pediatric patients with otitis media or respiratory, skin, and urinary tract infections. Against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis isolated and identified from otorrhea, epipharynx and rhinorrhea of pediatric patients with otitis media, the MIC90s of CVA/AMPC (1:14) in five years between 2006-2010 were 1 microg/mL for S. pneumoniae and 8 microg/mL for H. influenzae and 0.25-0.5microg/mL for M catarrhalis. The changes of MIC90s of CVA/AMPC (1:14) for penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase non-producing H. influenzae were two times, and no decrease in drug susceptibility was found in the period of the present investigation. In addition, the MIC changes of other antimicrobial agents for these three organisms were approximately two to four times as well. Against organisms isolated and identified from pus, sputum, pharynx, skin and urine of pediatric patients with respiratory, skin, and urinary tract infections, the MIC90s of CVA/AMPC (1:14) in four years between 2008-2011 were 1 microg/mL for S. pneumoniae, < or =0.06microg/mL for penicillin susceptible S. pneumoniae (PSSP) without any change, 0.5-1 microg/mL for penicillin intermediate resistant S. pneumoniae (PISP) with a twofold change and 1 microg/mL for PRSP with no change. The MIC90s of CVA/AMPC (1:14) were 2-8 microg/mL for S. aureus with a fourfold change, 2 microg/mL for methicillin-sensitive S. aureus without any change, 4-8 microg/mL for H. influenzae with a twofold change. Against beta-lactamase non-producing H. influenzae, MIC90s of CVA/AMPC (1:14) were 1 microg/mL for beta-lactamase negative ampicillin susceptible (BLNAS), 8 microg/mL for beta-lactamase negative ampicillin resistant (BLNAR), showing no change. Neither Streptococcus pyogenes or Klebsiella pneumoniae demonstrated any change and M. catarrhalis and Escherichia coli showed twofold changes of MIC90s of CVA/AMPC (1: 14). In the present investigation conducted to monitor annual changes in antibacterial activity intended for pediatric patients with otitis media or other infections, there was no significant change in antibacterial activity of CVA/AMPC (1: 14). PMID:24167843

Ishida, Atsuko; Hasegawa, Naomi; Okano, Hideyuki; Hara, Terufumi; Yoshida, Pascal

2013-06-01

58

Synthesis of a quinolone library from ynones  

PubMed Central

A library of 72 quinolones was synthesized from substituted anthranilic acids, using ynone intermediates. These masked ?-dicarbonyl synthons allowed cyclization under milder conditions than previously reported quinolone syntheses. PMID:20161410

Ward, Timothy R.; Turunen, Brandon J.; Haack, Torsten; Neuenswander, Benjamin; Shadrick, William; Georg, Gunda I.

2009-01-01

59

Synthesis of a quinolone library from ynones.  

PubMed

A library of 72 quinolones was synthesized from substituted anthranilic acids, using ynone intermediates. These masked ?-dicarbonyl synthons allowed cyclization under milder conditions than previously reported quinolone syntheses. PMID:20161410

Ward, Timothy R; Turunen, Brandon J; Haack, Torsten; Neuenswander, Benjamin; Shadrick, William; Georg, Gunda I

2009-11-25

60

Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria.  

PubMed

Peptide deformylase (PDF) has been identified as a promising target for novel antibacterial agents. In this study, a series of novel formyl hydroxyamino derivatives were designed and synthesized as PDF inhibitors and their antibacterial activities were evaluated. Among the potent PDF inhibitors (1o, 1q, 1o', 1q', and 1x), in vivo studies showed that compound 1q possesses mild toxicity, a good pharmacokinetic profile and protective effects. The good in vivo efficacy and low toxicity suggest that this class of compounds has potential for development and use in future antibacterial drugs. PMID:25151577

Yang, Shouning; Shi, Wei; Xing, Dong; Zhao, Zheng; Lv, Fengping; Yang, Liping; Yang, Yushe; Hu, Wenhao

2014-10-30

61

Studies of the photooxidant properties of antibacterial fluoroquinolones and their naphthalene derivatives.  

PubMed

We synthesized and determined the production of reactive oxygen species (ROS) as 1O2, *-O2, *OH, H2O2 during the photolysis with UV-A light of three antibacterial quinolones and their naphthyl ester derivatives. Singlet oxygen and ROS dose-dependant generation from norfloxacin (1), enoxacin (2), ciprofloxacin (3) and their respective naphthyl ester derivatives 4-6 were detecting in cell-free systems by the histidine assay and by luminol-enhanced chemiluminescence (LCL). Both the electronic absorption and emission spectra were quantified and their photostability determined. The antibacterial activity in darkness and under irradiation of compounds 4, 5 and 6 was tested on E. coli and compared with their parent drugs. PMID:19320285

Vargas, F; Zoltan, T; Ramirez, A H; Cordero, T; Chavez, V; Izzo, C; López, V; Cárdenas, Y M; Fernández, A; Hincapie, L; Fuentes, A

2009-02-01

62

Laser receptive polyelectrolyte thin films doped with biosynthesized silver nanoparticles for antibacterial coatings and drug delivery applications.  

PubMed

We report a simple method to fabricate multifunctional polyelectrolyte thin films to load and deliver the therapeutic drugs. The multilayer thin films were assembled by the electrostatic adsorption of poly (allylamine hydrochloride) (PAH) and dextran sulfate (DS). The silver nanoparticles (Ag NPs) biosynthesized from novel Hybanthus enneaspermus leaf extract as the reducing agent were successfully incorporated into the film. The biosynthesized Ag NPs showed excellent antimicrobial activity against the range of enteropathogens, which could be significantly enhanced when used with commercial antibiotics. The assembled silver nano composite multilayer films showed rupture and deformation when they are exposed to laser. The Ag NPs act as an energy absorption center, locally heat up the film and rupture it under laser treatment. The antibacterial drug, moxifloxacin hydrochloride (MH) was successfully loaded into the multilayer films. The total amount of MH release observed was about 63% which increased to 85% when subjected to laser light exposure. Thus, the polyelectrolyte thin film reported in our study has significant potential in the field of remote activated drug delivery, antibacterial coatings and wound dressings. PMID:24096301

Sripriya, Jaganathan; Anandhakumar, Sundaramurthy; Achiraman, Shanmugam; Antony, Jacob Joe; Siva, Durairaj; Raichur, Ashok M

2013-11-30

63

New quinolones in the treatment of joint and bone infections.  

PubMed

New quinolones are promising agents for use in the treatment of bone and joint infections because of their broad spectrum of activity against staphylococcal strains as well as gram-negative bacteria. Their pharmacologic properties and their availability for oral administration make them the drugs of choice in the treatment of such chronic infections. Pefloxacin and ciprofloxacin are the principal quinolones that have been evaluated with respect to the treatment of bone and joint infections. In the literature cited the mean rates of bacteriologic and clinical response among patients treated with pefloxacin and ciprofloxacin were 87.6% and 73%, respectively, whereas failure of therapy were due to the persistence of the causative organisms (5% and 15% of the cases, respectively) or to the emergence of resistant mutant strains (15% and 12% of the cases, respectively). Development of resistance to the quinolones--especially in staphylococci, Pseudomonas aeruginosa, Serratia, Enterobacter species, and Klebsiella pneumoniae--is a problem that can be reduced by the intelligent use of these potent agents in spite of the ease of their administration. Therapy that combines new quinolones with other antibiotics should prevent the emergence of resistant mutants, but this hypothesis has to be assessed in large studies. PMID:3279491

Desplaces, N; Acar, J F

1988-01-01

64

Antibacterial activities of Beilschmiedia obscura and six other Cameroonian medicinal plants against multi-drug resistant Gram-negative phenotypes  

PubMed Central

Background The rapid spread of bacteria expressing multi-drug resistance propels the search for new antibacterial agents. The present study was designed to evaluate the antibacterial activities of the methanol extracts from Beilschmiedia obscura and six other Cameroonian plants against a panel of twenty nine Gram-negative bacteria including Multi-drug resistant (MDR) phenotypes. Methods The phytochemical investigations of the extracts were carried out according to the standard methods and the liquid micro-dilution assay was used for all antibacterial assays. Results Phytochemical analysis showed the presence of alkaloids in all studied extracts. Other chemical classes of secondary metabolites such as anthocyanines, anthraquinones flavonoids, saponins, tannins, sterols and triterpenes were selectively detected in the extracts. The extract from the fruits of Beilschmiedia obscura, Pachypodanthium staudtii leaves and Peperomia fernandopoiana (whole plant) displayed the best spectrum of activity with MIC values ranging from 16 to 1024 ?g/mL against at least 65% and above of the tested bacteria. The extract from Beilschmiedia obscura was the most active with MIC values below 100 ?g/mL against ten of the tested bacteria. This extract also showed MBC values below 1024 ?g/mL against 55.17% of the studied microorganisms. Phenylalanine arginine ?-naphthylamide (PA?N) significantly modulated the activities of extracts from the leaves and fruits of Pachypodanthium staudtii and Beilschmiedia obscura respectively, by increasing their inhibitory activity against Klebsiella pneumoniae KP55 strain at least four fold. Conclusion The overall results of the present investigation provide information for the possible use of the methanol extracts of the studied plant species, especially B. obscura to fight infectious diseases caused by Gram-negative bacteria including MDR phenotypes. PMID:25023038

2014-01-01

65

A Bi-Mix Antibacterial Drug-Delivery System for Regenerative Endodontics. Jadesada Palasuk1  

E-print Network

to characterize mechanical, chemical and antibacterial properties. One-way ANOVA (only for fiber diameter strength was not significantly decreased compared to the control except G3. Average fiber diameters were in the nano-scaled range and significantly lower then the control. SEM imaging indicated a submicron fibrous

Zhou, Yaoqi

66

Assessment of Pseudomonas aeruginosa N5,N10-Methylenetetrahydrofolate Dehydrogenase - Cyclohydrolase as a Potential Antibacterial Drug Target  

PubMed Central

The bifunctional enzyme methylenetetrahydrofolate dehydrogenase – cyclohydrolase (FolD) is identified as a potential drug target in Gram-negative bacteria, in particular the troublesome Pseudomonas aeruginosa. In order to provide a comprehensive and realistic assessment of the potential of this target for drug discovery we generated a highly efficient recombinant protein production system and purification protocol, characterized the enzyme, carried out screening of two commercial compound libraries by differential scanning fluorimetry, developed a high-throughput enzyme assay and prosecuted a screening campaign against almost 80,000 compounds. The crystal structure of P. aeruginosa FolD was determined at 2.2 Å resolution and provided a template for an assessment of druggability and for modelling of ligand complexes as well as for comparisons with the human enzyme. New FolD inhibitors were identified and characterized but the weak levels of enzyme inhibition suggest that these compounds are not optimal starting points for future development. Furthermore, the close similarity of the bacterial and human enzyme structures suggest that selective inhibition might be difficult to attain. In conclusion, although the preliminary biological data indicates that FolD represents a valuable target for the development of new antibacterial drugs, indeed spurred us to investigate it, our screening results and structural data suggest that this would be a difficult enzyme to target with respect to developing the appropriate lead molecules required to underpin a serious drug discovery effort. PMID:22558288

Maluf, Fernando V.; McElroy, Stuart; James, Daniel; Frearson, Julie; Gray, David; Hunter, William N.

2012-01-01

67

Conformational, spectroscopic, and molecular dynamics DFT study of precursors for new potential antibacterial fluoroquinolone drugs.  

PubMed

Biological activity, functionality, and synthesis of (fluoro)quinolones is closely related to their precursors (for instance 3-fluoroanilinoethylene derivatives) (i.e., their functional groups, conformational behavior, and/or electronic structure). Herein, the theoretical study of 3-fluoroanilinoethylene derivatives is presented. Impact of substituents (acetyl, methyl ester, and ethyl ester) on the conformational analysis and the spectral behavior is investigated. The B3LYP/6-311++G** computational protocol is utilized. It is found that the intramolecular hydrogen bond N-H···O is responsible for the energetic preference of anti (a) conformer (anti position of 3-fluoroanilino group with respect to the C?C double bond). The Boltzmann ratios of the conformers are related to the differences of the particular dipole moments and/or their dependence on the solvent polarity. The studied acetyl, ethyl ester, and methyl ester substituted fluoroquinolone precursors prefer in the solvent either EZa, ZZa, or both conformers equally, respectively. In order to understand the degree of freedom of rotation of the trans ethyl ester group, B3LYP/6-311G** molecular dynamic simulations were carried out. Vibrational frequencies, electron transitions, as well as NMR spectra are analyzed with respect to conformational analysis, including the effect of the substituent. X-ray structures of the precursors are presented and compared with the results of the conformational analysis. PMID:25188903

Dorotíková, Sandra; Plevová, Kristína; Bu?inský, Lukáš; Mal?ek, Michal; Herich, Peter; Kucková, Lenka; Bobeni?ová, Miroslava; Soralová, Stanislava; Kožíšek, Jozef; Fronc, Marek; Milata, Viktor; Dvoranová, Dana

2014-10-01

68

Hierarchical nested trial design (HNTD) for demonstrating treatment efficacy of new antibacterial drugs in patient populations with emerging bacterial resistance.  

PubMed

In the last decade or so, pharmaceutical drug development activities in the area of new antibacterial drugs for treating serious bacterial diseases have declined, and at the same time, there are worries that the increased prevalence of antibiotic-resistant bacterial infections, especially the increase in drug-resistant Gram-negative infections, limits available treatment options . A recent CDC report, 'Antibiotic Resistance Threats in the United States', indicates that antimicrobial resistance is one of our most serious health threats. However, recently, new ideas have been proposed to change this situation. An idea proposed in this regard is to conduct randomized clinical trials in which some patients, on the basis of a diagnostic test, may show presence of bacterial pathogens that are resistant to the control treatment, whereas remaining patients would show pathogens that are susceptible to the control. The control treatment in such trials can be the standard of care or the best available therapy approved for the disease. Patients in the control arm with resistant pathogens can have the option for rescue therapies if their clinical signs and symptoms worsen. A statistical proposal for such patient populations is to use a hierarchical noninferiority-superiority nested trial design that is informative and allows for treatment-to-control comparisons for the two subpopulations without any statistical penalty. This design can achieve in the same trial dual objectives: (i) to show that the new drug is effective for patients with susceptible pathogens on the basis of a noninferiority test and (ii) to show that it is superior to the control in patients with resistant pathogens. This paper addresses statistical considerations and methods for achieving these two objectives for this design. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. PMID:24957660

Huque, Mohammad F; Valappil, Thamban; Soon, Guoxing Greg

2014-11-01

69

Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials  

PubMed Central

Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization. PMID:22435599

Zhang, Yiqun; Clark, Julie A; Connelly, Michele C.; Zhu, Fangyi; Min, Jaeki; Guiguemde, W. Armand; Pradhan, Anupam; Iyer, Lalitha; Furimsky, Anna; Gow, Jason; Parman, Toufan; El Mazouni, Farah; Phillips, Margaret A.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin

2012-01-01

70

1558 VOLUME 24 NUMBER 12 DECEMBER 2006 NATURE BIOTECHNOLOGY Riboswitches as antibacterial drug targets  

E-print Network

technology for riboswitch drug discovery and discuss the challenges that may face riboswitch drug discoverers that does not interfere with the expression of the adjacent open reading frame (ORF). When present, and members of each class bind to the same metabolite and share a highly conserved sequence and secondary

Cai, Long

71

In Vitro and In Vivo Antibacterial Activities of DK507k, a Novel Fluoroquinolone  

Microsoft Academic Search

The antibacterial activities of DK-507k, a novel quinolone, were compared with those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as sitafloxacin and was as active as or up to eightfold more active than gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae, methicillin-susceptible and methicillin-resistant Staphylo- coccus aureus, and coagulase-negative staphylococci. DK-507k was as

Tsuyoshi Otani; Mayumi Tanaka; Emi Ito; Yuichi Kurosaka; Yoichi Murakami; Kiyomi Onodera; Takaaki Akasaka; Kenichi Sato

2003-01-01

72

Influence of First-Line Antibiotics on the Antibacterial Activities of Acetone Stem Bark Extract of Acacia mearnsii De Wild. against Drug-Resistant Bacterial Isolates  

PubMed Central

Background. This study was aimed at evaluating the antibacterial activity of the acetone extract of A. mearnsii and its interactions with antibiotics against some resistant bacterial strains. Methods. The antibacterial susceptibility testing was determined by agar diffusion and macrobroth dilution methods while the checkerboard method was used for the determination of synergy between the antibiotics and the extract. Results. The results showed that the susceptibility of the different bacterial isolates was concentration dependent for the extract and the different antibiotics. With the exception of S. marcescens, the inhibition zones of the extract produced by 20?mg/mL ranged between 18 and 32?mm. While metronidazole did not inhibit any of the bacterial isolates, all the antibiotics and their combinations, except for ciprofloxacin and its combination, did not inhibit Enterococcus faecalis. The antibacterial combinations were more of being antagonistic than of being synergistic in the agar diffusion assay. From the macrobroth dilution, the extract and the antibiotics exerted a varied degree of inhibitory effect on the test organisms. The MIC values of the acetone extract which are in mg/mL are lower than those of the different antibiotics which are in ?g/mL. From the checkerboard assay, the antibacterial combinations showed varied degrees of interactions including synergism, additive, indifference, and antagonism interactions. While antagonistic and additive interactions were 14.44%, indifference interaction was 22.22% and synergistic interaction was 37.78% of the antibacterial combinations against the test isolates. While the additivity/indifference interactions indicated no interactions, the antagonistic interaction may be considered as a negative interaction that could result in toxicity and suboptimal bioactivity. Conclusion. The synergistic effects of the herbal-drug combinations may be harnessed for the discovery and development of more rational evidence-based drug combinations with optimized efficiency in the prevention of multidrug resistance and therapy of multifactorial diseases. PMID:25101132

Olajuyigbe, Olufunmiso O.; Coopoosamy, Roger M.

2014-01-01

73

Antibacterial effect of mango (Mangifera indica Linn.) leaf extract against antibiotic sensitive and multi-drug resistant Salmonella typhi.  

PubMed

Alternative herbal medicine has been used to treat various infections from centuries. Natural plants contain phytoconstituents having similar chemical properties as of synthetic antibiotics. Typhoid fever is a serious infection and failure of its treatment emerged multi-drug resistant (MDR) bugs of Salmonella typhi. Due to multiple and repeated issues with antibiotics efficacy, it became essential to evaluate biological properties of plants from different geographical origins. Mango leaves have been Reported for various medicinal effects like antioxidant, antimicrobial, antihelminthic, antidiabetic and antiallergic etc. Objective of present study was to investigate anti-typhoid properties of acetone mango leaf extract (AMLE) against antibiotic sensitive and MDR S. typhi isolates. A total of 50 isolates of S. typhi including MDR (n=30) and antibiotic sensitive (n=20) were investigated. Staphylococcus aureus (ATCC 25923) and Salmonella typhimurium (ATCC14028) were used as quality control strains. AMLE was prepared and its antibacterial activity was evaluated by agar well diffusion screening method and minimum inhibitory concentration (MIC), by agar dilution technique. Zone of inhibition (mm) of AMLE against MDR and antibiotic sensitive isolates was 18±1.5mm (Mean±S.D). Zone of S. aureus (ATCC 25923) and S. typhimurium (ATCC14028) was 20±1.5mm (Mean±S.D). MIC of AMLE was Reported in range from 10-50 mg/ml. The present study described the inhibitory effects of mango leaves against S. typhi. PMID:23811447

Hannan, Abdul; Asghar, Samra; Naeem, Tahir; Ikram Ullah, Muhammad; Ahmed, Ijaz; Aneela, Syeda; Hussain, Shabbir

2013-07-01

74

[Use of quinolones in the treatment of Pseudomonas aeruginosa infections in children with cystic fibrosis].  

PubMed

Quinolones, elective drugs for Pseudomonas aeruginosa (P. aeruginosa) pulmonary infections in Cystic Fibrosis (C.F.) patients, are controversially administered in prepuberal age for their arthropathic toxicity. We report the result of retrospective study on the use of quinolones in a group of 43 CF patients. The patients were divided into two groups: below 18 years (22 pts.) and over 18 (21 pts.). All patients were evaluated clinically with the scoring system Shwachman and Kulczyk. Ciprofloxacin and Ofloxacin (15/20 mg/kg/die) were administered. In 11.6% of the patients, all belonging to the second group, side effects, such as urticaria, tongue oedema, foreskin erythema, generalised erythema and itch, were described. No side effect has been reported in the patients below 18 years. Two patients complained knee arthralgias not related to the quinolones administration: in fact in the first case the demineralisation seemed to be responsible of the arthralgia, while in the second case an immunological disorder (ANA+, ICC+) should be involved in the pathogenesis of arthritis. Height velocity evaluation showed the same slowering of the CF untreated patients. In conclusion, our study confirms that quinolones use in indicated in severe and infective complications of CF on the basis of their efficacy, safety and their slight adverse effects similar to those of other potent antibiotic. Moreover our results confirm that no quinolone-induced cartilage toxicity is present in CF patients. PMID:7739928

Milio, M C; Campana, S

1995-01-01

75

Prediction of Quinolone Activity against Mycobacterium avium by Molecular Topology and Virtual Computational Screening  

PubMed Central

We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against Mycobacterium avium-M. intracellulare complex in order to develop a model capable of predicting the activity of new quinolones against the M. avium-M. intracellulare complex in vitro. Topological indices were used as structural descriptors and were related to anti-M. avium-M. intracellulare complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 24 quinolones, including recently developed fluoroquinolones, whose MICs were subsequently determined in vitro by using the Alamar blue microplate assay; the biological results confirmed the model's predictions. The MICs of these 24 quinolones were then treated by multilinear regression (MLR) to establish a model capable of classifying them according to their in vitro activities. Using this model, a good correlation between measured and predicted MICs was found (r2 = 0.88; r2cv [cross-validation correlation] = 0.82). Moxifloxacin, sparfloxacin, and gatifloxacin were the most potent against the M. avium- M. intracellulare complex, with MICs of 0.2, 0.4, and 0.9 ?g/ml, respectively. Finally, virtual modifications of these three drugs were evaluated in LDA and MLR models in order to determine the importance of different substituents in their activity. We conclude that the combination of molecular-topology methods, LDA, and MLR provides an excellent tool for the design of new quinolone structures with enhanced activity. PMID:10991858

Gozalbes, Rafael; Brun-Pascaud, Monique; Garcia-Domenech, Ramon; Galvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

2000-01-01

76

Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.  

PubMed

DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 ?) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases. PMID:24497635

Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

2014-05-01

77

Anti-Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Techniques  

PubMed Central

The apicoplast, a plastid-like organelle of Toxoplasma gondii, is thought to be a unique drug target for quinolones. In this study, we assessed the in vitro activity of quinolones against T. gondii and developed new quantitative structure-activity relationship models able to predict this activity. The anti-Toxoplasma activities of 24 quinolones were examined by means of linear discriminant analysis (LDA) using topological indices as structural descriptors. In parallel, in vitro 50% inhibitory concentrations (IC50s) were determined in tissue culture. A multilinear regression (MLR) analysis was then performed to establish a model capable of classifying quinolones by in vitro activity. LDA and MLR analysis were applied to virtual structures to identify the influence of each atom or substituent of the quinolone ring on anti-Toxoplasma activity. LDA predicted that 20 of the 24 quinolones would be active against T. gondii. This was confirmed in vitro for most of the quinolones. Trovafloxacin, grepafloxacin, gatifloxacin, and moxifloxacin were the quinolones most potent against T. gondii, with IC50s of 0.4, 2.4, 4.1, and 5.1 mg/liter, respectively. Using MLR analysis, a good correlation was found between measured and predicted IC50s (r2 = 0.87, cross-validation r2 = 0.74). MLR analysis showed that the carboxylic group at position C-3 of the quinolone ring was not essential for anti-Toxoplasma activity. In contrast, activity was totally dependent on the presence of a fluorine at position C-6 and was enhanced by the presence of a methyl group at C-5 or an azabicyclohexane at C-7. A nucleophilic substituent at C-8 was essential for the activity of gatifloxacin and moxifloxacin. PMID:10991859

Gozalbes, Rafael; Brun-Pascaud, Monique; Garcia-Domenech, Ramon; Galvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

2000-01-01

78

Antibacterial Sludge  

NSDL National Science Digital Library

Today, it's hard to find dishwashing liquids or hand soaps that don't advertise their "antibacterial" chemicals. But while it's unclear whether these chemicals actually help us, there's new reason to believe they might do more harm than good. This Science Update examines the common antibacterial agent, Triclocarban or TCC, which is found in hand soaps and other household products.

Science Update;

2004-10-04

79

Optimization of endochin-like quinolones for antimalarial activity  

PubMed Central

Structural analogs of the antimalarial Endochin were synthesized and screened for antiplasmodial activity against drug sensitive and multidrug resistant strains of Plasmodium falciparum. Structural features have been identified that are associated with improved potency while other features are associated with equipotency against an atovaquone-resistant clinical isolate. Relative to endochin the most active compound ELQ-121 shows ? 100-fold improvement in IC50 for inhibition of P. falciparum in vitro and it also exhibits enhanced metabolic stability. A polyethylene glycol carbonate ester prodrug of ELQ-121 demonstrated in vivo efficacy against P. yoelii in mice. This is the first report of an endochin-like quinolone that is efficacious in treating malaria in a mammalian host. PMID:21040724

Winter, Rolf; Kelly, Jane X.; Smilkstein, Martin J.; Hinrichs, David; Koop, Dennis R.; Riscoe, Michael K.

2010-01-01

80

Detection of quinolones in poultry meat obtained from retail centers in Santiago Province, the Dominican Republic.  

PubMed

In the Dominican Republic, poultry consumption per capita is greater than 34 kg of poultry meat per year. However, antibiotics, specifically the quinolone group, may be overused and can result in residues in the poultry meat. These residues are of concern because consumers may have allergies to antibiotics and antibiotic-resistant bacteria can develop from overuse of antibiotics in production. Little is known concerning this issue specifically for Santiago Province in the Dominican Republic. Thus, the main purpose of this research was to evaluate the incidence of residual quinolones in poultry meat and determine whether any residues detected were higher than the residue maximum limits (100 ?g/kg) established by food industry authorities, including the U.S. Food and Drug Administration and European Food Safety Authority. A total of 135 samples of chicken breast were taken from different retail meat centers in the nine municipalities of Santiago Province (Santiago, Tamboril, Sabana Iglesia, Villa Bisonó, Puñal, Villa González, Licey, Jánico, and San José De Las Matas) and were analyzed using the Equinox test (Immunotec, Swanton, VT). Of the 135 samples analyzed, 50% from Sabana Iglesia, 20% from Licey, 20% from San Jose De Las Matas, and 6.25% from Santiago contained residues of quinolones higher than the residue maximum limits. No quinolone residues were detected in samples obtained from Janico, Punal, Tamboril, Villa Bisono, or Villa Gonzalez. The results of this investigation suggest that some poultry meat sold for human consumption in Santiago Province of the Dominican Republic contains quinolone residues and may represent a health risk to some consumers. PMID:23433388

Silfrany, R O; Caba, R E; Solís de Los Santos, F; Hanning, I

2013-02-01

81

Virulence Factors in Urinary Escherichia coli Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance?  

PubMed Central

Quinolone- and fluoroquinolone-resistant Escherichia coli strains harbor fewer virulence factors than susceptible strains. The reasons underlying this correlation are incompletely understood. We investigated the phylogenetic background, the presence of the papC, hlyA, and cnf1 (pathogenicity island IIJ96-associated), fimA, iss, and iutA genes, and the presence of type 1 fimbriae, P fimbriae, and hemolysin in 243 urinary E. coli isolates resistant only to quinolones (8%), resistant to both quinolones and fluoroquinolones (51%), or susceptible to both drugs (41%). Group B2 accounted for 56% of the isolates, showing a significantly higher prevalence among fluoroquinolone-susceptible strains than among resistant strains (65% versus 50% [P = 0.03]). hly and cnf1 were significantly more associated with susceptibility (P < 0.001) and with group B2 (P < 0.001 for group B2 versus groups A and D). However, within group B2, fluoroquinolone-resistant strains showed lower prevalences of papC, hlyA, and cnf1 than their susceptible counterparts (P < 0.001). In contrast, the incidence of iutA appeared higher for refractory isolates, including group B2, than for susceptible isolates (P < 0.001). Only in group B2 did fluoroquinolone-resistant strains reveal a lesser ability to agglutinate Saccharomyces cerevisiae (7%) than quinolone-resistant (87%) and susceptible (80%) isolates, despite uniform possession of fimA genes. No similar contrast emerged for expression of hemolysin and P fimbriae. Mutations conferring quinolone and fluoroquinolone resistance may thus require a particular genetic background, not strictly correlated with phylogenetic groups. More interestingly, the mutational event itself can affect the expression of type 1 fimbriae, at least in the prevalent and complex B2 strains. PMID:18057134

Piatti, Gabriella; Mannini, Alessandro; Balistreri, Maria; Schito, Anna Maria

2008-01-01

82

Setting and Revising Antibacterial Susceptibility Breakpoints  

PubMed Central

Clinical microbiology laboratories need to communicate results of antibacterial susceptibility testing to prescribers. Sophisticated prescribers who are knowledgeable of the pharmacokinetics and pharmacodynamics of antibacterials may desire no more information than the MIC of the drug in question. However, most prescribers require interpretation of antibacterial susceptibility testing results. Breakpoints can assist in determining if an antibacterial is potentially useful in the treatment of a bacterial infection. Breakpoints should be set prior to an antibacterial being used clinically. Breakpoint setting requires integration of knowledge of the wild-type distribution of MICs, assessment of the pharmacokinetics/pharmacodynamics of the antibacterial, and study of the clinical outcome of infections when the antibacterial is used. It is mandatory that breakpoints be reviewed when antibacterial agents have been in clinical use for some time, particularly if mechanisms of bacterial resistance to the drug have been described. In general, greater amounts of information on the pharmacokinetics and pharmacodynamics of an antibacterial are available when breakpoints need to be revised. However, the opportunity to conduct randomized clinical studies of an antibacterial declines after the drug has been released commercially. Well-designed observational clinical studies are therefore necessary in order to provide reliable data to inform those reevaluating breakpoints. Breakpoint-setting organizations may also play a role in developing phenotypic tests for detection of resistance mechanisms, as this information may complement use of the breakpoint in some circumstances. PMID:17630331

Turnidge, John; Paterson, David L.

2007-01-01

83

Spectrofluorometric determination of certain quinolone through charge transfer complex formation  

Microsoft Academic Search

A spectrofluorimetric method was developed for the determination of three fluoroquinolones antibacterials, namely, ofloxacin (OFL), levofloxacin (LEV), lomefloxacin (LOM), and pipemidic acid (PIP) through charge transfer (CT) complex formation with 7,7,8,8-tetracyanoquinodimethane (TCNQ). TCNQ was found to react with these drugs to produce stable complexes and the fluorescence intensity of the complexes was enhanced in 15–90 times higher than that of

Li Ming Du; Ya Qin Yang; Qing Mei Wang

2004-01-01

84

Morphology, drug release, antibacterial, cell proliferation, and histology studies of chamomile-loaded wound dressing mats based on electrospun nanofibrous poly(?-caprolactone)/polystyrene blends.  

PubMed

For the first time, it has been tried to achieve optimum conditions for electrospun poly(?-caprolactone)/polystyrene (PCL/PS) nanofibrous samples as active wound dressings containing chamomile via D-optimal design approach. In this work, systematic in vitro and in vivo studies were carried out by drug release rate, antibacterial and antifungal evaluations, cell culture, and rat wound model along with histology observation. The optimized samples were prepared under the following electrospinning conditions: PCL/PS ratio (65/35), PCL concentration 9%(w/v), PS concentration 14%(w/v), distance between the syringe needle tip and the collector 15.5 cm, applied voltage 18 kV, and solution flow rate 0.46 mL h(-1) . The FE-SEM micrographs showed electrospun PCL/PS (65/35) nanofibrous sample containing 15% chamomile had a minimum average diameter (?175 nm) compared to the neat samples (?268 nm). The drug released resulted in a gradual and high amount of chamomile from the optimized PCL/PS nanofibrous sample (?70%) in respect to PCL and PS nanofibers after 48 h. This claim was also confirmed by antibacterial and antifungal evaluations in which an inhibitory zone with a diameter of about 7.6 mm was formed. The rat wound model results also indicated that the samples loaded with 15% chamomile extract were remarkably capable to heal the wounds up to 99?±?0.5% after 14 days post-treatment periods. The adhesion of mesenchymal stem cells and their viability on the optimized samples were confirmed by MTT analysis. Also, the electrospun nanofibrous mats based on PCL/PS (65/35) showed a high efficiency in the wound closure and healing process compared to the reference sample, PCL/PS nanofibers without chamomile. Finally, the histology analysis revealed that the formation of epithelial tissues, the lack of necrosis and collagen fibers accumulation in the dermis tissues for the above optimized samples. PMID:24259351

Motealleh, Behrooz; Zahedi, Payam; Rezaeian, Iraj; Moghimi, Morvarid; Abdolghaffari, Amir Hossein; Zarandi, Mohammad Amin

2014-07-01

85

Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 2: Antibacterial and Osteoblastic Response  

PubMed Central

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time scales on bacterial and osteoblastic cell cultures. All CAP powders exhibited satisfying antibacterial performance against Staphylococcus aureus, the main causative agent of osteomyelitis. Still, owing to its highest drug adsorption efficiency, the most bacteriostatically effective phase was amorphous CAP with the minimal inhibitory concentration of less than 1 mg/ml. At the same time, the positive cell response and osteogenic effect of the antibiotic-loaded CAP particles was confirmed in vitro for all the sparsely soluble CAP phases. Adsorption of the antibiotic onto CAP particles reversed the deleterious effect that the pure antibiotic exerted on the osteogenic activity of the osteoblastic cells. The simultaneous osteogenic and antimicrobial performance of the material developed in this study, altogether with its ability to exhibit sustained drug release, may favor its consideration as a material base for alternative therapeutic approaches to prolonged antibiotic administration and surgical debridement typically prescribed in the treatment of osteomyelitis. PMID:23115128

Uskokovic, Vuk; Desai, Tejal A.

2012-01-01

86

Review article Mechanisms of quinolone resistance in Salmonella  

E-print Network

Review article Mechanisms of quinolone resistance in Salmonella Axel CLOECKAERT*, Elisabeth CHASLUS-negative bacteria, mechanisms of resistance to quinolones in Salmonella include target gene mutations, active efflux resistance mechanisms in Salmonella by comparison with that of E. coli and future directions of research

Paris-Sud XI, Université de

87

Regional variations in quinolone use in France and associated factors.  

PubMed

The purpose of this study was to investigate geographic variations in the use of quinolones in France and their associated factors. All reimbursement claims of antimicrobials were collected for 90 % of the French population for the year 2007. Dispensed quantities were then converted into defined daily doses (DDD) and adjusted for the age structure of the national population. Correlations between quinolone use and total antimicrobial use and some morbidity and socio-economic factors were studied using Spearman's rank correlation coefficients. On average, 2.05 DDD of quinolones per 1,000 inhabitants per day (DID) were dispensed in 2007 in France, accounting for 10.2 % of the total antimicrobial consumption in adults. A 40 % variation was observed between the regions with the lowest (1.73 DID) and the highest use (2.44 DID). This variation was more important for anti-pneumococcal quinolones than for quinolones directed against urinary tract infections (coefficients of variation: 26 vs. 6 %). Quinolone use was correlated with some regional socio-economic factors (unemployment, growth domestic product, health expenditures) and physician density, but was independent of the total antimicrobial use. After adjustment for age, large variations in quantitative and qualitative quinolone use were observed across French regions, especially for anti-pneumococcal fluoroquinolones. These results, though not controlled for potential epidemics variations, argue in favour of a possible improvement in quinolone prescribing to be achieved in some regions. PMID:22644054

Gallini, A; Taboulet, F; Bourrel, R

2012-11-01

88

Palladium(II) complexes as biologically potent metallo-drugs: synthesis, spectral characterization, DNA interaction studies and antibacterial activity.  

PubMed

Four novel mononuclear Pd(II) complexes have been synthesized with the biologically active Schiff base ligands (L1-L4) derived from 3-amino-2-methyl-4(3H)-quinazolinone. The structure of the complexes has been proposed by elemental analysis, molar conductance, IR, (1)H NMR, mass, UV-Vis spectrometric and thermal studies. The investigation of interaction of the complexes with calf thymus DNA (CT-DNA) has been performed with absorption and fluorescence spectroscopic studies. The nuclease activity was done using pUC19 supercoiled DNA by gel-electrophoresis. All the ligands and their Pd(II) complexes have also been screened for their antibacterial activity by discolor diffusion technique. PMID:23416915

Prasad, Kollur Shiva; Kumar, Linganna Shiva; Chandan, Shivamallu; Naveen Kumar, R M; Revanasiddappa, Hosakere D

2013-04-15

89

Anti-inflammatory drugs interacting with Zn (II) metal ion based on thiocyanate and azide ligands: Synthesis, spectroscopic studies, DFT calculations and antibacterial assays  

NASA Astrophysics Data System (ADS)

Zinc (II) complexes with non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (nap) and ibuprofen (ibu) were synthesized in the presence of nitrogen donor ligands (thiocyanate or azide). The complexes were characterized by elemental analysis, FT-IR, 1H NMR and UV-Vis spectroscopes. The binding modes of the ligands in complexes were established by means of molecular modeling of the complexes, and calculation of their IR, NMR and absorption spectra at DFT (TDDFT)/B3LYP level were studied. The experimental and calculated data verified monodentate binding through the carboxylic oxygen atoms of anti-inflammatory drugs in the zinc complexes. The calculated 1H, FT-IR and UV-Vis data are in better agreement with the experimental results, and confirm the predicted tetrahedral structures for the Zn (II) complexes. In addition to DFT calculations of complexes, natural bond orbital (NBO) was performed at B3LYP/6-31+G(d,p) level of theory. Biological studies showed the antibacterial activity of zinc complexes against Gram-positive and Gram-negative bacterial strains.

Chiniforoshan, Hossein; Tabrizi, Leila; Hadizade, Morteza; Sabzalian, Mohammad R.; Chermahini, Alireza Najafi; Rezapour, Mehdi

2014-07-01

90

Quinolones in the treatment of Salmonella carriers.  

PubMed

Infections caused by Salmonella typhi are commonly followed by a chronic carrier state despite positive clinical and initial bacteriologic responses. The use of primary antibiotics like chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole has several major drawbacks, including in some instances the failure to prevent the carrier state. The appearance worldwide of strains with multiple resistance to the most commonly used regimens has prompted the search for new forms of therapy. Among the agents studied have been third-generation cephalosporins and quinolones, which are active in vitro against bacterial enteropathogens like S. typhi. Resolution of chronic carriage of S. typhi and other salmonellae is difficult, and regimens commonly fail (including those that combine antibiotic administration with removal of the gallbladder). In addition to being active in vitro against Salmonella species, the newer quinolones adequately penetrate the intestinal lumen, liver, bile, and gallbladder. Initial experience with norfloxacin and ciprofloxacin in oral treatment of the chronic S. typhi carrier state in adults has been promising. PMID:2672248

Rodríguez-Noriega, E; Andrade-Villanueva, J; Amaya-Tapia, G

1989-01-01

91

Dynamics of Quinolone Resistance in Fecal Escherichia coli of Finishing Pigs after Ciprofloxacin Administration  

PubMed Central

ABSTRACT Escherichia coli resistance to quinolones has now become a serious issue in large-scale pig farms of China. It is necessary to study the dynamics of quinolone resistance in fecal Escherichia coli of pigs after antimicrobial administration. Here, we present the hypothesis that the emergence of resistance in pigs requires drug accumulation for 7 days or more. To test this hypothesis, 26 pigs (90 days old, about 30 kg) not fed any antimicrobial after weaning were selected and divided into 2 equal groups: the experimental (EP) group and control (CP) group. Pigs in the EP group were orally treated daily with 5 mg ciprofloxacin/kg of body weight for 30 days, and pigs in the CP group were fed a normal diet. Fresh feces were collected at 16 time points from day 0 to day 61. At each time point, ten E. coli clones were tested for susceptibility to quinolones and mutations of gyrA and parC. The results showed that the minimal inhibitory concentration (MIC) for ciprofloxacin increased 16-fold compared with the initial MIC (0.5 µg/ml) after ciprofloxacin administration for 3 days and decreased 256-fold compared with the initial MIC (0.5 µg/ml) after ciprofloxacin withdrawal for 26 days. GyrA (S83L, D87N/ D87Y) and parC (S80I) substitutions were observed in all quinolone-resistant E. coli (QREC) clones with an MIC ?8 µg/ml. This study provides scientific theoretical guidance for the rational use of antimicrobials and the control of bacterial resistance. PMID:24919413

HUANG, Kang; XU, Chang-Wen; ZENG, Bo; XIA, Qing-Qing; ZHANG, An-Yun; LEI, Chang-Wei; GUAN, Zhong-Bin; CHENG, Han; WANG, Hong-Ning

2014-01-01

92

Febrile Urinary Tract Infection After Prostate Biopsy and Quinolone Resistance  

PubMed Central

Purpose Complications after prostate biopsy have increased and various causes have been reported. Growing evidence of increasing quinolone resistance is of particular concern. In the current retrospective study, we evaluated the incidence of infectious complications after prostate biopsy and identified the risk factors. Materials and Methods The study population included 1,195 patients who underwent a prostate biopsy between January 2007 and December 2012 at Chung-Ang University Hospital. Cases of febrile UTI that occurred within 7 days were investigated. Clinical information included age, prostate-specific antigen, prostate volume, hypertension, diabetes, body mass index, and biopsy done in the quinolone-resistance era. Patients received quinolone (250 mg intravenously) before and after the procedure, and quinolone (250 mg) was orally administered twice daily for 3 days. We used univariate and multivariate analysis to investigate the predictive factors for febrile UTI. Results Febrile UTI developed in 39 cases (3.1%). Core numbers increased from 2007 (8 cores) to 2012 (12 cores) and quinolone-resistant bacteria began to appear in 2010 (quinolone-resistance era). In the univariate analysis, core number?12 (p=0.024), body mass index (BMI)>25 kg/m2 (p=0.004), and biopsy done in the quinolone-resistance era (p=0.014) were significant factors. However, in the multivariate analysis adjusted for core number, the results were not significant, with the exception of BMI>25 kg/m2 (p=0.011) and biopsy during the quinolone-resistance era (p=0.035), which were significantly associated with febrile UTI. Conclusions Quinolone resistance is the main cause of postbiopsy infections in our center. We suggest that further evaluation is required to validate similar trends. Novel strategies to find alternative prophylactic agents are also necessary.

Choi, Joong Won; Chang, In Ho; Kim, Kyung Do; Moon, Young Tae; Myung, Soon Chul; Kim, Jin Wook; Kim, Min Su; Kwon, Jong Kyou

2014-01-01

93

Challenges of Antibacterial Discovery  

PubMed Central

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

Silver, Lynn L.

2011-01-01

94

Orally Bioavailable 6-Chloro-7-methoxy-4(1H)-quinolones Efficacious against Multiple Stages of Plasmodium.  

PubMed

The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days. PMID:25148516

Cross, R Matthew; Flanigan, David L; Monastyrskyi, Andrii; LaCrue, Alexis N; Sáenz, Fabián E; Maignan, Jordany R; Mutka, Tina S; White, Karen L; Shackleford, David M; Bathurst, Ian; Fronczek, Frank R; Wojtas, Lukasz; Guida, Wayne C; Charman, Susan A; Burrows, Jeremy N; Kyle, Dennis E; Manetsch, Roman

2014-11-13

95

Electrochemical evaluation of antibacterial drugs as environment-friendly inhibitors for corrosion of carbon steel in HCl solution  

NASA Astrophysics Data System (ADS)

The effect of penicillin G, ampicillin and amoxicillin drugs on the corrosion behavior of carbon steel (ASTM 1015) in 1.0 mol L-1 hydrochloric acid solution was investigated using potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and electrochemical noise (EN) techniques. The inhibition efficiency was found to increase with increasing inhibitor concentration. The effect of temperature on the rate of corrosion in the absence and presence of these drugs was also studied. Some thermodynamic parameters were computed from the effect of temperature on corrosion and inhibition processes. Adsorption of these inhibitors was found to obey Langmuir adsorption isotherm. There was a case of mixed mode of adsorption here but while penicillin was adsorbed mainly through chemisorption, two other drugs were adsorbed mainly through physisorption. Potentiodynamic polarization measurements indicated that the inhibitors were of mixed type. In addition, this paper suggests that the electrochemical noise (EN) technique under open circuit conditions as the truly noninvasive electrochemical method can be employed for the quantitative evaluation of corrosion inhibition. This was done by using the standard deviation of partial signal (SDPS) for calculation of the amount of noise charges at the particular interval of frequency, thereby obtaining the inhibition efficiency (IE) of an inhibitor. These IE values showed a reasonable agreement with those obtained from potentiodynamic polarization and EIS measurements.

Golestani, Gh.; Shahidi, M.; Ghazanfari, D.

2014-07-01

96

NATURE BIOTECHNOLOGY VOLUME 24 NUMBER 12 DECEMBER 2006 1497 Antibacterial discovery and development--  

E-print Network

NATURE BIOTECHNOLOGY VOLUME 24 NUMBER 12 DECEMBER 2006 1497 Antibacterial discovery and development in the ongoing battle against infectious disease. Antibacterial drugs have been the most effective of all exacerbated by the cessation, or at the very least downsizing, of antibacterial drug discovery efforts

Cai, Long

97

Death Inducing and Cytoprotective Autophagy in T-47D Cells by Two Common Antibacterial Drugs: Sulfathiazole and Sulfacetamide  

PubMed Central

The broad spectrum of the pharmacological effects of sulfonamide family of drugs motivated us to investigate the cellular mechanisms for anti-cancer effects of sulfathiazole and sulfacetamide on T-47D breast cancer cells. Fluorescent microscopy, flow cytometric analysis, caspase-3 activity and DNA fragmentation assays were used to detect apoptosis. The distribution of the cells among different phases of the cell cycle was measured by flow cytometry. The expression of several genes with important roles in some critical cellular pathways including apoptosis, mTOR/AKT pathway and autophagy were determined by real time RT-PCR analysis. Sulfathiazole and sulfacetamide induced anti-proliferative effects on T-47D cells were independent of apoptosis and cell cycle arrest. The overexpression of critical genes involved in autophagy including ATG5, p53 and DRAM indicated that the main effect of the drug-induced anti-proliferative effects was through induction of autophagy. This process was induced in 2 different forms, including death inducing and cytoprotective autophagy. Sulfathiazole treatment was followed by higher expression of p53/DRAM and downregulation of Akt/ mTOR pathway resulting in death autophagy. In contrast, sulfacetamide treatment lowered expression of p53/DRAM pathway in parallel with upregulation of Akt/mTOR pathway promoting cytoprotective autophagy. The results indicated that autophagy is the main mechanism mediating the anti-cancer effects of sulfathiazole and sulfacetamide on T-47D cells. Alignment of the p53 and DRAM expression along with activation level of Akt survival pathway therefore determines the type of autophagy that occurs. PMID:23450781

Mohammadpour, Raziye; Safarian, Shahrokh; Sheibani, Nader; Norouzi, Saeed; Razazan, Atefeh

2013-01-01

98

Sequence-motif Detection of NAD(P)-binding Proteins: Discovery of a Unique Antibacterial Drug Target  

NASA Astrophysics Data System (ADS)

Many enzymes use nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate (NAD(P)) as essential coenzymes. These enzymes often do not share significant sequence identity and cannot be easily detected by sequence homology. Previously, we determined all distinct locally conserved pyrophosphate-binding structures (3d motifs) from NAD(P)-bound protein structures, from which 1d sequence motifs were derived. Here, we aim to establish the precision of these 3d and 1d motifs to annotate NAD(P)-binding proteins. We show that the pyrophosphate-binding 3d motifs are characteristic of NAD(P)-binding proteins, as they are rarely found in nonNAD(P)-binding proteins. Furthermore, several 1d motifs could distinguish between proteins that bind only NAD and those that bind only NADP. They could also distinguish between NAD(P)-binding proteins from nonNAD(P)-binding ones. Interestingly, one of the pyrophosphate-binding 3d and corresponding 1d motifs was found only in enoyl-acyl carrier protein reductases, which are enzymes essential for bacterial fatty acid biosynthesis. This unique 3d motif serves as an attractive novel drug target, as it is conserved across many bacterial species and is not found in human proteins.

Hua, Yun Hao; Wu, Chih Yuan; Sargsyan, Karen; Lim, Carmay

2014-09-01

99

Sequence-motif Detection of NAD(P)-binding Proteins: Discovery of a Unique Antibacterial Drug Target  

PubMed Central

Many enzymes use nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate (NAD(P)) as essential coenzymes. These enzymes often do not share significant sequence identity and cannot be easily detected by sequence homology. Previously, we determined all distinct locally conserved pyrophosphate-binding structures (3d motifs) from NAD(P)-bound protein structures, from which 1d sequence motifs were derived. Here, we aim to establish the precision of these 3d and 1d motifs to annotate NAD(P)-binding proteins. We show that the pyrophosphate-binding 3d motifs are characteristic of NAD(P)-binding proteins, as they are rarely found in nonNAD(P)-binding proteins. Furthermore, several 1d motifs could distinguish between proteins that bind only NAD and those that bind only NADP. They could also distinguish between NAD(P)-binding proteins from nonNAD(P)-binding ones. Interestingly, one of the pyrophosphate-binding 3d and corresponding 1d motifs was found only in enoyl-acyl carrier protein reductases, which are enzymes essential for bacterial fatty acid biosynthesis. This unique 3d motif serves as an attractive novel drug target, as it is conserved across many bacterial species and is not found in human proteins. PMID:25253464

Hua, Yun Hao; Wu, Chih Yuan; Sargsyan, Karen; Lim, Carmay

2014-01-01

100

In vitro antibacterial activity of some antihistaminics belonging to different groups against multi-drug resistant clinical isolates  

PubMed Central

Antihistaminics are widely used for various indications during microbial infection. Hence, this paper investigates the antimicrobial activities of 10 antihistaminics belonging to both old and new generations using multiresistant Gram-positive and Gram-negative clinical isolates. The bacteriostatic activity of antihistaminics was investigated by determining their MIC both by broth and agar dilution techniques against 29 bacterial strains. Azelastine, cyproheptadine, mequitazine and promethazine were the most active among the tested drugs. Diphenhydramine and cetirizine possessed weaker activity whereas doxylamine, fexofenadine and loratadine were inactive even at the highest tested concentration (1 mg/ml). The MIC of meclozine could not be determined as it precipitated with the used culture media. The MBC values of antihistaminics were almost identical to the corresponding MIC values. The bactericidal activity of antihistaminics was also studied by the viable count technique in sterile saline solution. Evident killing effects were exerted by mequitazine, meclozine, azelastine and cyproheptadine. Moreover, the dynamics of bactericidal activity of azelastine were studied by the viable count technique in nutrient broth. This activity was found to be concentration-dependant. This effect was reduced on increasing the inoculum size while it was increased on raising the pH. The post-antimicrobial effect of 100 ?g/ml azelastine was also determined and reached up to 3.36 h. PMID:24031715

El-Nakeeb, Moustafa A.; Abou-Shleib, Hamida M.; Khalil, Amal M.; Omar, Hoda G.; El-Halfawy, Omar M.

2011-01-01

101

In vitro susceptibility of quinolone-resistant Campylobacter jejuni to new macrolide antibiotics  

Microsoft Academic Search

The MICs of erythromycin and three new macrolide antibiotics were determined for 36 quinolone-susceptible and 106 quinolone-resistantCampylobacter jejuni. The MIC90 values of azithromycin, clarithromycin, roxithromycin and erythromycin were 0.5, 4, 16 and 4 mg\\/l respectively. No difference was found between macrolide activity against the quinolone-susceptible and the quinolone-resistant strains. Clarithromycin and especially azithromycin might eventually replace erythromycin for the treatment

H. P. Endtz; M. Broeren; R. P. Mouton

1993-01-01

102

Alterations in the DNA Topoisomerase IVgrlAGene Responsible for Quinolone Resistance inStaphylococcus aureus  

Microsoft Academic Search

A 4.2-kb DNA fragment conferring quinolone resistance was cloned from a quinolone-resistant clinical isolate of Staphylococcus aureus and was shown to possess a part of the grlB gene and a mutated grlA gene. S-803F and E-843K mutations in thegrlAgene product were responsible for the quinolone resistance. The mutatedgrlAgenes responsible for quinolone resistance were dominant over the wild-type allele, irrespective of

JUN-ICHI YAMAGISHI; TSUYOSHI KOJIMA; YOSHIHIRO OYAMADA; KOUICHI FUJIMOTO; HIROAKI HATTORI; SHINICHI NAKAMURA; ANDMATSUHISA INOUE

1996-01-01

103

Plasmid-Mediated Quinolone Resistance in Clinical Isolates of Escherichia coli from Shanghai, China  

Microsoft Academic Search

Although quinolone resistance usually results from chromosomal mutations, recent studies indicate that quinolone resistance can also be plasmid mediated. The gene responsible, qnr, is distinct from the known quinolone resistance genes and in previous studies seemed to be restricted to Klebsiella pneumoniae and Escherichia coli isolates from the University of Alabama in Birmingham, where this resistance was discovered. In Shanghai,

Minggui Wang; John H. Tran; George A. Jacoby; Yingyuan Zhang; Fu Wang; David C. Hooper

2003-01-01

104

Antistaphylococcal Activity of DX-619, a New Des-F(6)-Quinolone, Compared to Those of Other Agents  

PubMed Central

The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC50s/MIC90s (?g/ml) against 131 Staphylococcus aureus strains (?0.002 to 2.0/0.06/0.5) and 128 coagulase-negative staphylococci (0.004 to 0.25/0.016/0.125). Among strains tested, 76 S. aureus strains and 51 coagulase-negative staphylococci were resistant to ciprofloxacin. DX-619 had the lowest MIC50/MIC90 values against 127 quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/>32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 ?g/ml and sitafloxacin at 1.0 ?g/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 ?g/ml after <50 days of selection compared to 16 to >32 ?g/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4× MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains. PMID:16048943

Bogdanovich, Tatiana; Esel, Duygu; Kelly, Linda M.; Bozdogan, Bulent; Credito, Kim; Lin, Gengrong; Smith, Kathy; Ednie, Lois M.; Hoellman, Dianne B.; Appelbaum, Peter C.

2005-01-01

105

Antistaphylococcal activity of DX-619, a new des-F(6)-quinolone, compared to those of other agents.  

PubMed

The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC(50)s/MIC(90)s (microg/ml) against 131 Staphylococcus aureus strains (quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/>32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 microg/ml and sitafloxacin at 1.0 microg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 microg/ml after <50 days of selection compared to 16 to >32 microg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4x MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains. PMID:16048943

Bogdanovich, Tatiana; Esel, Duygu; Kelly, Linda M; Bozdogan, Bülent; Credito, Kim; Lin, Gengrong; Smith, Kathy; Ednie, Lois M; Hoellman, Dianne B; Appelbaum, Peter C

2005-08-01

106

Effect of Anaerobic Growth on Quinolone Lethality with Escherichia coli?  

PubMed Central

Quinolone activity against Escherichia coli was examined during aerobic growth, aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid, norfloxacin, ciprofloxacin, and PD161144 were lethal for cultures growing aerobically, and the bacteriostatic activity of each quinolone was unaffected by anaerobic growth. However, lethal activity was distinct for each quinolone with cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic acid failed to kill cells under both conditions; norfloxacin killed cells when they were grown anaerobically but not when they were treated with chloramphenicol; ciprofloxacin killed cells under both conditions but required higher concentrations than those required with cells grown aerobically; and PD161144, a C-8-methoxy fluoroquinolone, was equally lethal under all conditions. Following pretreatment with nalidixic acid, a shift to anaerobic conditions or the addition of chloramphenicol rapidly blocked further cell death. Formation of quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS)-dependent drop in cell lysate viscosity, occurred during aerobic and anaerobic growth and in the presence and in the absence of chloramphenicol. However, lethal chromosome fragmentation, detected as a drop in viscosity in the absence of SDS, occurred with nalidixic acid treatment only under aerobic conditions in the absence of chloramphenicol. With PD161144, chromosome fragmentation was detected when the cells were grown aerobically and anaerobically and in the presence and in the absence of chloramphenicol. Thus, all quinolones tested appear to form reversible bacteriostatic complexes containing broken DNA during aerobic growth, during anaerobic growth, and when protein synthesis is blocked; however, the ability to fragment chromosomes and to rapidly kill cells under these conditions depends on quinolone structure. PMID:17043118

Malik, Muhammad; Hussain, Syed; Drlica, Karl

2007-01-01

107

Identification and Characterization of a Type III Polyketide Synthase Involved in Quinolone Alkaloid Biosynthesis from Aegle marmelos Correa*  

PubMed Central

Quinolone alkaloids, found abundantly in the roots of bael (Aegle marmelos), possess various biological activities and have recently gained attention as potential lead molecules for novel drug designing. Here, we report the characterization of a novel Type III polyketide synthase, quinolone synthase (QNS), from A. marmelos that is involved in the biosynthesis of quinolone alkaloid. Using homology-based structural modeling, we identify two crucial amino acid residues (Ser-132 and Ala-133) at the putative QNS active site. Substitution of Ser-132 to Thr and Ala-133 to Ser apparently constricted the active site cavity resulting in production of naringenin chalcone from p-coumaroyl-CoA. Measurement of steady-state kinetic parameters demonstrates that the catalytic efficiency of QNS was severalfold higher for larger acyl-coenzymeA substrates as compared with smaller precursors. Our mutagenic studies suggest that this protein might have evolved from an evolutionarily related member of chalcone synthase superfamily by mere substitution of two active site residues. The identification and characterization of QNS offers a promising target for gene manipulation studies toward the production of novel alkaloid scaffolds. PMID:23329842

Resmi, Mohankumar Saraladevi; Verma, Priyanka; Gokhale, Rajesh S.; Soniya, Eppurathu Vasudevan

2013-01-01

108

Changing patterns in sensitivity of causative organisms of septicaemia in children: the need for quinolones.  

PubMed

A review of the pattern, and antibiotic sensitivities of blood culture isolates over a 3 year period in children presenting to the Paediatric Unit of Ahmadu Bello University Teaching Hospital, Kaduna is reported. Positive blood culture isolates were obtained in 26.9% of 1,982 children. The most prevalent isolates were Staphylococcus aureus (59.9%), Escherichia coli (16.9%) and Klebsiella (16.3%). There was a striking paucity of isolation of Salmonella typhi (1.3%) and Streptococcus. Sensitivity to commonly used drugs like ampicillin/cloxacillin, genticin, ceftazidime and chloramphenicol was low (8.0-50.0%), with a corresponding delayed fever resolution and prolonged hospital stay. 31.0-83.3% of the isolates were highly sensitive to pefloxacin, norfloxacin and ofloxacin, which were not generally recommended for use in paediatric patients. In two patients with no response to commonly used antibiotics, use of quinolones lysed their fever within 48 hours. This change of antibiotic sensitivity patterns calls for a thorough investigation into the potential role of these quinolones in paediatric chemotherapeutics either singly or in appropriate combinations with existing antibiotics. PMID:15490798

Orogade, A A; Akuse, R M

2004-03-01

109

Antibacterials in Household Products  

MedlinePLUS

... the Prudent Use of Antibiotics Antibacterials in household products What exactly is an antibacterial? How is it ... cleaners. Did you know that over 1000 commercial products contain triclosan or other biocide agents? Established in ...

110

Effect of heating on the stability of quinolones in milk.  

PubMed

Nowadays, the possible public health risk associated with the presence of quinolone residues and other antibiotics in milk is well-known, but there is a lack of information about the effect milk processing temperatures have on the presence of antimicrobial residues. The aim of this work was to determine the effect of different temperatures and heating times on the concentration of quinolones in milk by employing liquid chromatographic equipment analysis with fluorescence detection. In order to determine the thermo-stability of these compounds, the first-order kinetic model was applied, and the activation energies, half-lives, and percentages of degradation of each compound were calculated. Results showed that quinolones are very resistant to different heat treatments with maximum losses of concentration of 12.71% for ciprofloxacin and 12.01% for norfloxacin at 120 degrees C and 20 min. The high stability of quinolones represents a significant risk to human health because the residues of these antibiotics can remain in milk after heat treatment and, therefore, can reach the dairy industry and consumers. PMID:20397732

Roca, M; Castillo, M; Marti, P; Althaus, R L; Molina, M P

2010-05-12

111

Longitudinal surveillance of outpatient quinolone antimicrobial use in Canada  

PubMed Central

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is important. OBJECTIVE: To assess the use of quinolone antimicrobials within Canadian provinces over time. METHODS: Antimicrobial prescribing data collected by IMS Health Canada were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and were used to calculate two yearly metrics: prescriptions per 1000 inhabitant-days and the mean defined daily doses (DDDs) per prescription. These measures were used to produce linear mixed models to assess differences among provinces and over time, while accounting for repeated measurements. RESULTS: The quinolone class of antimicrobials is used similarly among Canadian provinces. Year-to-year increases in quinolone prescribing occurred from 1995 to 2010, with a levelling off in the latter years. Year-to-year decreases in the DDDs per prescription were found to be significant from 2000 to 2010. DISCUSSION: Although the overall use of antimicrobials differs significantly among Canadian provinces, the use of the quinolone class does not vary at the provincial level. Results suggest that prescribing of ciprofloxacin may be a potential target for antimicrobial stewardship programs; however, decreases in the average DDDs per prescription suggest continued uptake of appropriate treatment guidelines. PMID:24855478

Glass-Kaastra, Shiona K; Finley, Rita; Hutchinson, Jim; Patrick, David M; Weiss, Karl; Conly, John

2014-01-01

112

Antibacterial activity of cefquinome against equine bacterial pathogens  

Microsoft Academic Search

Cefquinome is known for its use as an antibacterial drug in cattle and pigs. The objective of this study was to evaluate the antibacterial activity of cefquinome against equine pathogenic bacteria. The minimum inhibitory concentration (MIC) of cefquinome was determined for a total of 205 strains, which had recently been isolated in Europe from diseased horses (respiratory infection, foal septicaemia).

E. Thomas; V. Thomas; C. Wilhelm

2006-01-01

113

In vitro release of new quinolones from biodegradable systems: a comparative study.  

PubMed

A new biodegradable delivery system based on low molecular weight poly(lactic acid) has been formulated, with potential application in the sustained antibiotic release against bone infection. The in vitro release of two new quinolones (ofloxacin and ciprofloxacin) from the biodegradable matrix showed that the delivery of ofloxacin from the matrix lasted fifty-six days, whereas that of ciprofloxacin lasted fifty-one days. In both cases, release is controlled by the drug diffusion and the matrix degradation, the latter being the most critical factor. The obtained concentration levels are well above the Minimum Inhibitory Concentration (MIC) against the major causative bacteria of osteomyelitis. This fact in combination with the good reproducibility of measurements indicated that the system studied could be of value for the preparation of implantable controlled release systems for treatment of diseases in the bone system. PMID:8859405

Andreopoulos, A G; Korakis, T; Dounis, E; Anastasiadis, A; Tzivelekis, P; Kanellakopoulou, K

1996-04-01

114

Distinguishing importation from diversification of quinolone-resistant Neisseria gonorrhoeae by molecular evolutionary analysis  

Microsoft Academic Search

BACKGROUND: Distinguishing the recent introduction of quinolone resistant gonococci into a population from diversification of resistant strains already in the population is important for planning effective infection control strategies. We applied molecular evolutionary analyses to DNA sequences from 9 housekeeping genes and gyrA, parC and porB of 24 quinolone resistant N. gonorrhoeae (QRNG) and 24 quinolone sensitive isolates collected in

Marcos Pérez-Losada; Keith A Crandall; Margaret C Bash; Michael Dan; Jonathan Zenilman; Raphael P Viscidi

2007-01-01

115

Selection of drugs to treat gastro-oesophageal reflux disease: the role of drug interactions.  

PubMed

Gastro-oesophageal reflux disease is probably the most common acid-peptic disease in Western countries, and the successful treatment of mild to moderate disease with pharmacotherapy has become commonplace. A large number of effective drugs are now available, and so the decision-making process for physicians increasingly relies on considerations other than pure efficacy. Cost, adverse effects and drug interactions have therefore become important, particularly in the most vulnerable patients - children, the elderly and patients who are ill and are taking medications that may influence the efficacy of antireflux therapy. Important drug interactions with antacids include the prevention of the absorption of antibacterials such as tetracycline, azithromycin and quinolones. H2 antagonists, proton pump inhibitors and prokinetic agents undergo metabolism by the cytochrome P450 (CYP) system present in the liver and gastrointestinal tract. Cimetidine is an inhibitor of CYP3A and it may cause significant interactions with drugs of narrow therapeutic range and low bioavailability that are metabolised by these enzymes. The gastroparietal proton pump inhibitors lansoprazole, omeprazole and pantoprazole are all primarily metabolised by a genetically polymorphic enzyme, CYP2C19, that is absent from approximately 3% of Caucasians and 20% of Asians. These drugs may also interact with CYP3A, but to a lesser extent. Interactions with prokinetic agents carry the greatest potential for harm. Metoclopramide is a dopamine antagonist that may cause extrapyramidal effects when administered alone at high concentrations, or when coadministered with antipsychotic agents such as haloperidol or phenothiazines. Cisapride is clearly able to prolong the electrocardiographic QT interval and cause lethal ventricular arrhythmias when its metabolism is slowed by interaction with inhibitors of CYP3A, such as erythromycin, ketoconazole or itraconazole. PMID:11069215

Flockhart, D A; Desta, Z; Mahal, S K

2000-10-01

116

Quinolone and Cephalosporin Resistance in Enteric Fever  

PubMed Central

Enteric fever is a major public health problem in developing countries. Ciprofloxacin resistance has now become a norm in the Indian subcontinent. Novel molecular substitutions may become frequent in future owing to selective pressures exerted by the irrational use of ciprofloxacin in human and veterinary therapeutics, in a population endemic with nalidixic acid-resistant strains. The therapeutics of ciprofloxacin-resistant enteric fever narrows down to third- and fourth-generation cephalosporins, azithromycin, tigecycline and penems. The first-line antimicrobials ampicillin, chloramphenicol and co-trimoxazole need to be rolled back. Antimicrobial surveillance coupled with molecular analysis of fluoroquinolone resistance is warranted for reconfirming novel and established molecular patterns for therapeutic reappraisal and for novel-drug targets. This review explores the antimicrobial resistance and its molecular mechanisms, as well as novel drugs in the therapy of enteric fever. PMID:20927288

Capoor, Malini Rajinder; Nair, Deepthi

2010-01-01

117

Effective antibacterials: at what cost? The economics of antibacterial resistance and its control.  

PubMed

The original and successful business model of return on investment being sufficiently attractive to the pharmaceutical industry to encourage development of new antibacterial molecules and related diagnostics has been compromised by increasing development costs and regulatory hurdles, resulting in a decreasing chance of success and financial return. The supply of new effective agents is diminishing along with the number of companies engaged in antibacterial research and development. The BSAC Working Party on The Urgent Need:Regenerating Antibacterial Drug Discovery and Development identified the need to establish, communicate and apply the true health and economic value of antibacterials, along with the adoption of meaningful incentives, as part of the future model for antibacterial development. Robust data are needed on the cost of resistance and ineffective treatment of bacterial infection, along with national and local holistic analyses of the cost-benefit of antibacterials. An understanding of the true health and economic value of antibacterials and the cost of resistance across healthcare systems needs to be generated, communicated and used in order to set a pricing and reimbursement structure that is commensurate with value. The development and economic model of antibacterial use needs to be rebuilt based on this value through dialogue with the various stakeholders, including the pharmaceutical industry, and alternative incentives from 'push' to 'pull' and funding models, such as public/private partnerships, agreed. A research and development model that succeeds in developing and delivering new antibacterial agents that address the health needs of society from start to finish, 'from cradle to grave', must be established. PMID:21700625

White, Anthony R

2011-09-01

118

Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria  

PubMed Central

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc1. Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria. PMID:22566611

Biagini, Giancarlo A.; Fisher, Nicholas; Shone, Alison E.; Mubaraki, Murad A.; Srivastava, Abhishek; Hill, Alisdair; Antoine, Thomas; Warman, Ashley J.; Davies, Jill; Pidathala, Chandrakala; Amewu, Richard K.; Leung, Suet C.; Sharma, Raman; Gibbons, Peter; Hong, David W.; Pacorel, Benedicte; Lawrenson, Alexandre S.; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Stocks, Paul A.; Nixon, Gemma L.; Chadwick, James; Hemingway, Janet; Delves, Michael J.; Sinden, Robert E.; Zeeman, Anne-Marie; Kocken, Clemens H. M.; Berry, Neil G.; O'Neill, Paul M.; Ward, Stephen A.

2012-01-01

119

Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria.  

PubMed

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc(1). Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria. PMID:22566611

Biagini, Giancarlo A; Fisher, Nicholas; Shone, Alison E; Mubaraki, Murad A; Srivastava, Abhishek; Hill, Alisdair; Antoine, Thomas; Warman, Ashley J; Davies, Jill; Pidathala, Chandrakala; Amewu, Richard K; Leung, Suet C; Sharma, Raman; Gibbons, Peter; Hong, David W; Pacorel, Bénédicte; Lawrenson, Alexandre S; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Stocks, Paul A; Nixon, Gemma L; Chadwick, James; Hemingway, Janet; Delves, Michael J; Sinden, Robert E; Zeeman, Anne-Marie; Kocken, Clemens H M; Berry, Neil G; O'Neill, Paul M; Ward, Stephen A

2012-05-22

120

A new efficient route to 7-aryl-6-fluoro-8-nitroquinolones as potent antibacterial agents.  

PubMed

A series of 7-aryl-6-fluoro-8-nitroquinolones (6a-e) were synthesized through a novel, simple and clean synthetic procedure, through a Suzuki-Miyaura reaction. The target compounds were evaluated in vitro for their antimicrobial properties against bacterial and fungal strains. All of them showed antibacterial activity higher than the activity of ciprofloxacin, both towards Gram positive Bacillus subtilis and Staphylococcus aureus, and Gram negative Haemophilus influenzae strains. Compound 6d, containing the trisubstituted 7-aryl moiety, emerged as the most active quinolone derivative with MIC values ranging from 0.00007 ?g/mL to 0.015 ?g/mL. PMID:25180924

Al-Trawneh, Salah A; El-Abadelah, Mustafa M; Al-Abadleh, Mohammad M; Zani, Franca; Incerti, Matteo; Vicini, Paola

2014-10-30

121

Single- and multiple-dose pharmacokinetics of fleroxacin, a trifluorinated quinolone, in humans.  

PubMed Central

Fleroxacin (Ro 23-6240; AM-833) is a new trifluorinated quinolone exhibiting high activity against a broad spectrum of gram-negative and gram-positive bacteria. Healthy male volunteers received, according to a randomized scheme, oral doses of 200, 400, or 800 mg of fleroxacin in tablet form, an intravenous infusion of 100 mg, or 400 mg of fleroxacin orally together with 1,000 mg of probenecid. Fleroxacin is characterized pharmacokinetically by a long elimination half-life (9 to 10 h) and high concentrations in plasma (e.g., maximum concentration of 2.3 micrograms/ml after an oral dose of 200 mg). The volume of distribution clearly exceeds 1 liter/kg and suggests a good tissue penetration. Within 60 h, the cumulative urinary recovery of unchanged drug amounted to 50 to 60% of the dose. The renal clearance of unbound drug was 137 ml/min, and probenecid had no significant effect on renal elimination. A good linear correlation (r = 0.999) was found between doses from 100 to 800 mg and the resulting values of area under the concentration-time curve. The absolute bioavailability of the administered tablet was practically 100%. During oral multiple dosing of 800 or 1,200 mg of fleroxacin once a day over 10 consecutive days, the accumulation of the drug in plasma was close to the theoretically predicted value of 1.3 and reflected the persistence of linear pharmacokinetics. PMID:3125788

Weidekamm, E; Portmann, R; Suter, K; Partos, C; Dell, D; Lücker, P W

1987-01-01

122

Identification, Design and Biological Evaluation of Bisaryl Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)  

PubMed Central

A program was undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with a range of chemoinformatics methods in the rational selection of 17?000 compounds for high-throughput screening. Twelve distinct chemotypes were identified and briefly examined leading to the selection of the quinolone core as the key target for structure–activity relationship (SAR) development. Extensive structural exploration led to the selection of 2-bisaryl 3-methyl quinolones as a series for further biological evaluation. The lead compound within this series 7-chloro-3-methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl)quinolin-4(1H)-one (CK-2-68) has antimalarial activity against the 3D7 strain of P. falciparum of 36 nM, is selective for PfNDH2 over other respiratory enzymes (inhibitory IC50 against PfNDH2 of 16 nM), and demonstrates low cytotoxicity and high metabolic stability in the presence of human liver microsomes. This lead compound and its phosphate pro-drug have potent in vivo antimalarial activity after oral administration, consistent with the target product profile of a drug for the treatment of uncomplicated malaria. Other quinolones presented (e.g., 6d, 6f, 14e) have the capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc1, and studies to determine the potential advantage of this dual-targeting effect are in progress. PMID:22364416

2012-01-01

123

Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium  

PubMed Central

The mechanism of quinolone resistance in Mycoplasma genitalium remains poorly understood due to difficulties with in vitro culture, especially of clinical isolates. In this study, to confirm the association between mutations in topoisomerases and antimicrobial susceptibilities to quinolones, ciprofloxacin-resistant mutant strains were selected using the cultivable type strain ATCC 33530. Sequence analysis revealed that the mutant strains harbored mutations in topoisomerase IV: Gly81Cys in ParC, Pro261Thr in ParC, or Asn466Lys in ParE. The MICs of all quinolones tested against the mutant strains were 2- to 16-fold higher than those against the wild-type strain. No cross-resistance was observed with macrolides or tetracyclines. We determined the inhibitory activities of quinolones against DNA gyrase and topoisomerase IV in order to investigate the correlation between antimicrobial susceptibility and inhibitory activity against the target enzymes, considered the primary targets of quinolones. Furthermore, using enzymatic analysis, we confirmed that Gly81Cys in the ParC quinolone resistance-determining region (QRDR) contributed to quinolone resistance. This is the first study to isolate quinolone-resistant mutant strains of M. genitalium harboring substitutions in the parC or parE gene in vitro and to measure the inhibitory activities against the purified topoisomerases of M. genitalium. PMID:23357772

Takei, Masaya; Kishii, Ryuta; Yasuda, Mitsuru; Deguchi, Takashi

2013-01-01

124

Antibacterial activities of multi drug resistant Myroides odoratimimus bacteria isolated from adult flesh flies (Diptera: sarcophagidae) are independent of metallo beta-lactamase gene  

PubMed Central

Flesh flies (Diptera: Sarcophagidae) are well known cause of myiasis and their gut bacteria have never been studied for antimicrobial activity against bacteria. Antimicrobial studies of Myroides spp. are restricted to nosocomial strains. A Gram-negative bacterium, Myroides sp., was isolated from the gut of adult flesh flies (Sarcophaga sp.) and submitted to evaluation of nutritional parameters using Biolog GN, 16S rRNA gene sequencing, susceptibility to various antimicrobials by disc diffusion method and detection of metallo ?-lactamase genes (TUS/MUS). The antagonistic effects were tested on Gram-negative and Gram-positive bacteria isolated from human clinical specimens, environmental samples and insect mid gut. Bacterial species included were Aeromonas hydrophila, A. culicicola, Morganella morganii subsp. sibonii, Ochrobactrum anthropi, Weissella confusa, Escherichia coli, Ochrobactrum sp., Serratia sp., Kestersia sp., Ignatzschineria sp., Bacillus sp. The Myroides sp. strain was resistant to penicillin-G, erythromycin, streptomycin, amikacin, kanamycin, gentamycin, ampicillin, trimethoprim and tobramycin. These strain showed antibacterial action against all bacterial strains except W. confusa, Ignatzschineria sp., A. hydrophila and M. morganii subsp. sibonii. The multidrug resistance of the strain was similar to the resistance of clinical isolates, inhibiting growth of bacteria from clinical, environmental and insect gut samples. The metallo ?-lactamase (TUS/MUS) genes were absent, and resistance due to these genes was ruled out, indicating involvement of other secretion machinery. PMID:24031236

Dharne, M.S.; Gupta, A.K.; Rangrez, A.Y.; Ghate, H.V.; Patole, M.S.; Shouche, Y.S.

2008-01-01

125

Antibacterial activity of local herbs collected from Murree (Pakistan) against multi-drug resistant Klebsiella pneumonae, E. coli and methyciline resistant Staphylococcus aureus.  

PubMed

Exploring healing power in plants emerged in prehistory of human civilization. Sustaining good health has been achieved over the millions of years by use of plant products in various traditional sockets. A major contribution of medicinal plants to health care systems is their limitless possession of bioactive components that stimulate explicit physiological actions. Luckily Pakistan is blessed with huge reservoir of plants with medicinal potential and some of them; we focused in this study for their medicinal importance.In this study we checked the antibacterial activity inherent in Ricinus communis, Solanum nigrum, Dodonaea viscose and Berberis lyceum extracts for multidrug resistance bacterial strains Klebsiella pneumonae, E. coli and methyciline resistant Staphylococcus aureus. MRSA showed sensitivity for Ricinus communis. Multidrug resistant Klebsiella pneumonae was sensitive with Pine roxburgii and Ricinus communis but weakly susceptible for Solanum nigrum. Multidrug resistant E. coli was resistant to all plant extracts. Treatment of severe infections caused by the bacterial strains used in this study with Ricinus communis, Pine roxburgii and Solanum nigrum can lower the undesired side effects of synthetic medicine and also reduce the economic burden. PMID:23811466

Mansoor, Qaisar; Shaheen, Saira; Javed, Uzma; Shaheen, Uzma; Iqrar, Irum; Ismail, Muhammad

2013-07-01

126

Sophorolipids as antibacterial agents.  

PubMed

Sophorolipids (SLs), glycolipids produced by yeasts, have been reported to have immunomodulating activity and to reduce the mortality rate in animal models of sepsis. In the present study, the antibacterial activities of SLs and several derivatives were tested against a selection of standard bacterial isolates using the broth microdilution method. The SL derivatives tested did not show any significant antibacterial activity in vitro when tested at clinically relevant concentrations. Most likely the reported decrease of mortality rate in the rat septic shock model was not secondary to antibacterial activity of SLs. The SLs may be used as anti-inflammatory agents or immunomodulators without affecting the host's bacterial flora. PMID:19201743

Sleiman, Joseph N; Kohlhoff, Stephan A; Roblin, Patricia M; Wallner, Sabine; Gross, Richard; Hammerschlag, Margaret R; Zenilman, Michael E; Bluth, Martin H

2009-01-01

127

Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents.  

PubMed

DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC(50), 0.016 microg/ml; MIC(90), 0.03 microg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. beta-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 microg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2x MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days. PMID:16723567

Kosowska-Shick, Klaudia; Credito, Kim; Pankuch, Glenn A; Lin, Gengrong; Bozdogan, Bülent; McGhee, Pamela; Dewasse, Bonifacio; Choi, Dong-Rack; Ryu, Jei Man; Appelbaum, Peter C

2006-06-01

128

Antipneumococcal Activity of DW-224a, a New Quinolone, Compared to Those of Eight Other Agents  

PubMed Central

DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC50, 0.016 ?g/ml; MIC90, 0.03 ?g/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. ?-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 ?g/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2× MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days. PMID:16723567

Kosowska-Shick, Klaudia; Credito, Kim; Pankuch, Glenn A.; Lin, Gengrong; Bozdogan, Bulent; McGhee, Pamela; Dewasse, Bonifacio; Choi, Dong-Rack; Ryu, Jei Man; Appelbaum, Peter C.

2006-01-01

129

In vitro activities of pazufloxacin, a novel injectable quinolone, against bacteria causing infections in obstetric and gynecological patients.  

PubMed

T-3762 is an injectable new quinolone with a broad spectrum of antibacterial activity. Pazufloxacin (T-3761) is an active form of T-3762. The minimal inhibitory concentrations (MICs) of pazufloxacin for 50% of the clinical isolates tested were 3.13 microg/ml for Streptococcus agalactiae, 6.25 microg/ml for Gardnerella vaginalis, 0.025 microg/ml for Escherichia coli, 0.78 microg/ml for Pseudomonas aeruginosa, 6.25 microg/ml for Peptostreptococcus magnus, 6.25 microg/ml for Bacteroides fragilis and 12.5 microg/ml for Prevotella bivia. The MICs of T-3762 for 90% of the clinical isolates tested were 3.13 microg/ml for S. agalactiae, 6.25 microg/ml for G. vaginalis, 0.10 microg/ml for E. coli, 12.5 microg/ml for P. aeruginosa, 25 microg/ml for P. magnus, 12.5 microg/ml for B. fragilis and 25 microg/ml for P. bivia. The results of this study suggest that, subject to confirmation by clinical trials, T-3762, in combination with an agent with reliable activity against anaerobic bacteria, is suitable as an empirical therapy of patients with obstetric and gynecological infections. PMID:10224336

Mikamo, H; Sato, Y; Hayasaki, Y; Kawazoe, K; Tamaya, T

1999-01-01

130

Interaction of Bacteriocin-Capped Silver Nanoparticles with Food Pathogens and Their Antibacterial Effect  

Microsoft Academic Search

With the emergence of multiple-drug-resistant pathogens, the antibacterial property of silver in colloidal form has emerged as a potential candidate for combating infectious diseases. A combination of antibacterial agents along with nanosilver could prove to be more potent due to broadened antibacterial spectrum with possibly lower doses. In the present study, a facile single-step green method of synthesizing silver nanoparticles

Tarun Kumar Sharma; Mahak Sapra; Aradhana Chopra; Rekha Sharma; Supriya Deepak Patil; Ravinder Kumar Malik; Ranjana Pathania; Naveen Kumar Navani

2012-01-01

131

Molecular Investigation of Quinolone Resistance of Quinolone Resistance-Determining Region in Streptococcus pneumoniae Strains Isolated from Iran Using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Method  

PubMed Central

Objectives The resistance of Streptococcus pneumoniae to the recently available antibiotic treatment has been a growing problem. The aim of the study was to determine the quinolone-resistant strains and detect the presence of mutations in the quinolone resistance-determining regions of the gyrA, parE, and parC genes. Methods In this study, for the first time in Iran, the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was used to investigate the presence of mutations at quinolone resistance-determining regions of topoisomerase IV and DNA gyrase on 82 S. pneumoniae strains, among them 45 clinical samples were from patients and 37 from healthy carriers (control group). Results In clinical samples, 34 (75.56%) strains contained mutations in the parC gene, 31 (68.89%) carried mutations in the gyrA gene, and 14 (31.11%) had parE gene mutations. Antibiotic susceptibility test was performed using the CLSI (Clinical and Laboratory Standards Institute) criteria on three different generations of quinolone family, with nalidixic acid (82.22%) showing the highest resistance and levofloxacin (42.22%) the least resistance. Conclusion Results indicated that there is a significant correlation between quinolone resistance development and mutations in the parE gene as well as in the parC and gyrA genes.

Kargar, Mohammad; Moein Jahromi, Fataneh; Doosti, Abbas; Handali, Somayeh

2014-01-01

132

Antibacterial Effect of Diclofenac Sodium on Enterococcus faecalis  

PubMed Central

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) have shown antibacterial activity in some recent studies. The aim of this study was to evaluate the antibacterial effect of diclofenac against Enterococcus faecalis (E. faecalis) as a resistant endodontic bacterium in comparison with ibuprofen, calcium hydroxide and amoxicillin. Materials and Methods: The antibacterial activity of materials was evaluated using agar diffusion test and tube dilution method. Mixtures of 400 mg/ml of materials were prepared. The bacteria were seeded on 10 Muller-Hinton agar culture plates. Thirty microliter of each test material was placed in each well punched in agar plates. After incubation, the zone of bacterial inhibition was measured. Minimum inhibitory concentration (MIC) of the test materials was determined by agar dilution method. One-way Analysis of Variance (ANOVA) followed by Sidak post hoc test was used to compare the mean zone of microbial growth in the groups. Results: There were significant differences between the two groups (p< 0.05). Results of the agar diffusion test showed that antibiotics (amoxicillin, gentamycin) had the greatest antibacterial activity followed by NSAIDs (ibuprofen, diclofenac). Ca(OH)2 failed to show antibacterial activity. Diclofenac and ibuprofen showed distinct antibacterial activity against E. faecalis in 50 ?g/ml and above concentrations. Conclusion: Within the limitations of this in vitro study, it is concluded that diclofenac and ibuprofen have significantly more pronounced antibacterial activity against E. faecalis in comparison with Ca(OH)2. PMID:23724199

Salem-Milani, Amin; Balaei-Gajan, Esrafil; Rahimi, Saeed; Moosavi, Zohreh; Abdollahi, Ardalan; Zakeri-Milani, Parvin; Bolourian, Mehrdad

2013-01-01

133

Mass Spectra and X-Ray Powder Diffraction Studies on Some Ethanolamine and Quinolone Complexes  

Microsoft Academic Search

The mass spectra and X-ray powder diffraction studies of some ethanolamine and 2-quinolone complexes are discussed. The fragmentation pattern and mode of bonding were suggested. The data were explained based on the molecular structure.

Mohyi M. El-essawi; Mamdouh S. Masoud; Amira M. Amr

1990-01-01

134

Optical control of antibacterial activity  

NASA Astrophysics Data System (ADS)

Bacterial resistance is a major problem in the modern world, stemming in part from the build-up of antibiotics in the environment. Novel molecular approaches that enable an externally triggered increase in antibiotic activity with high spatiotemporal resolution and auto-inactivation are highly desirable. Here we report a responsive, broad-spectrum, antibacterial agent that can be temporally activated with light, whereupon it auto-inactivates on the scale of hours. The use of such a ‘smart’ antibiotic might prevent the build-up of active antimicrobial material in the environment. Reversible optical control over active drug concentration enables us to obtain pharmacodynamic information. Precisely localized control of activity is achieved, allowing the growth of bacteria to be confined to defined patterns, which has potential for the development of treatments that avoid interference with the endogenous microbial population in other parts of the organism.

Velema, Willem A.; van der Berg, Jan Pieter; Hansen, Mickel J.; Szymanski, Wiktor; Driessen, Arnold J. M.; Feringa, Ben L.

2013-11-01

135

Antibacterial and anticandidal screening of Tunisian Citrullus colocynthis Schrad. from Medenine  

Microsoft Academic Search

Ethnopharmacological relevanceResistance to current antibacterial drugs and the rise of opportunistic fungal infections are growing global concerns. Traditional medicine is a potential source of new antibacterials and antifungals. Citrullus colocynthis Schrad. (Cucurbitaceae) endemic in Southern Tunisia, is used in folk medicine against dermatological, gynaecological and pulmonary infections.

Belsem Marzouk; Zohra Marzouk; Rachel Décor; Hayet Edziri; Ehsen Haloui; Nadia Fenina; Mahjoub Aouni

2009-01-01

136

Nutritional and antibacterial treatments of live food organisms : the influence on survival,  

E-print Network

Nutritional and antibacterial treatments of live food organisms : the influence on survival, growth-Pée-sur-Nivelle, F 64310 Ascain Summary After ingestion of nutrients and/or antibacterial drug, live food organisms the live food organisms had not been enriched, survival on day 45 was between 5 and 14 p. 100, and the mean

Paris-Sud XI, Université de

137

Antibacterial activity of the recombinant antimicrobial peptide Ib-AMP4 from Impatiens balsamina and its synergy with other antimicrobial agents against drug resistant bacteria.  

PubMed

Ib-AMP4 is an antimicrobial peptide of Impatiens balsamina (Balsaminaceae). Ib-AMP4 was produced as a recombinant peptide and in this study its antimicrobial activity against human bacterial pathogens was investigated. Ib-AMP4 was bactericidal against both Gram positive and Gram negative bacteria with MIC values between 0.49 and 3.5 microM in sensitive species. A genuine synergistic effect was achieved when IB-AMP4 was employed in combination with the plant monoterpene thymol against drug-resistant Klebsiella pneumoniae (KPC) ATCC700603, or with the antibiotics vancomycin or oxacillin against Enterococcus faecalis (VRE) ATCC51299. PMID:23923648

Fan, X; Reichling, J; Wink, M

2013-07-01

138

Targeting FtsZ for antibacterial therapy: a promising avenue.  

PubMed

The widespread problem of bacterial resistance towards existing drugs and the paucity of effective drugs for the treatment of bacterial infections have prompted the scientific community to think about novel strategies for discovering new classes of antibacterial drugs. Target-based screening of inhibitory molecules has emerged as an important alternative for the development of potent antibacterials. FtsZ is a prokaryotic cytoskeleton protein, which plays an important role in bacterial cell division. It forms a highly dynamic Z-ring at the centre of the cell and recruits other accessory proteins, which are involved in bacterial cytokinesis. Here, we discuss the assembly dynamics of FtsZ and the key features that place it among the novel antibacterial drug targets. The recent progress in finding the inhibitors of functional properties of FtsZ and its interactions with other proteins, which has been enabled by advanced screening methods and structure-based design, are presented herein. Although there are significant challenges in the development of this new class of antibacterial drugs, nonetheless the therapeutic potential of FtsZ as a drug target is motivating researchers to find lead molecules with enhanced efficacy and reduced toxicity. PMID:19659446

Kapoor, Sonia; Panda, Dulal

2009-09-01

139

Evaluation of antibacterial activity of extracts of five species of wood-colonizing fungi.  

PubMed

Screening new organisms for antibacterial activity and searching for new antibacterial drugs is important due to the constant generation of new antibiotic-resistant strains of pathogenic bacteria. An E. coli broth microdilution test was used to evaluate the results of the Vibrio fischeri bioluminescence test in five of the most antibacterially active species of wood-colonizing fungi. Serpula lacrymans was found to be a potential source of thermostable antibiotic(s) and the Vibrio fischeri bioluminescence test was confirmed to be a useful method for screening for antibacterial activity. PMID:16721880

Janes, Damjan; Umek, Andrej; Kreft, Samo

2006-01-01

140

Detection of the Pseudomonas Quinolone Signal (PQS) by cyclic voltammetry and amperometry using a boron doped diamond electrode.  

PubMed

2-Heptyl-3-hydroxy-4-quinolone, known as the Pseudomonas Quinolone Signal, is a key regulator of bacterial cooperative behaviour known as quorum sensing. A simple electrochemical strategy was employed for its sensitive detection using a bare boron-doped diamond electrode by cyclic voltammetry and amperometry. PQS (and potentially other quinolones) was then detected in cultures of P. aeruginosa pqsL(-) mutant strains. PMID:21853180

Zhou, Lin; Glennon, Jeremy D; Luong, John H T; Reen, F Jerry; O'Gara, Fergal; McSweeney, Christina; McGlacken, Gerard P

2011-10-01

141

Drugs.  

ERIC Educational Resources Information Center

This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

Hurst, Hunter, Ed.; And Others

1984-01-01

142

Green synthesis of silver nanoparticles from leaf extract of Mimusops elengi, Linn. for enhanced antibacterial activity against multi drug resistant clinical isolates.  

PubMed

Green synthesis of metallic silver nanoparticles has attracted nowadays and alternative to physical and chemical approaches. In the present study, silver nanoparticles (AgNPs) were synthesized from leaf extract of Mimusops elengi, L. at room temperature. Formation of stable AgNPs at 1mM concentrations of silver nitrate (AgNO3) typically gave spherical shape particles with diameter range from 55 to 83nm. The kinetic properties of particle formation were proportional to the effect of concentration of AgNO3 solution. In order to identify the compounds responsible for the bioreduction of Ag(+) ion and the stabilization of AgNPs produced, the functional group present in Mimusops elengi, L. leaf extract was investigated using FTIR. The formation of nanoparticle was confirmed using the surface plasmon resonance band shown in UV-vis spectrophotometer. The topography and morphology of the particles were determined using scanning electron microscopy. The crystalline nature of nanoparticles was confirmed from the XRD pattern. Furthermore these green synthesized AgNPs were found to show higher antimicrobial efficacy against multi drug resistant clinical isolates. PMID:23563291

Prakash, P; Gnanaprakasam, P; Emmanuel, R; Arokiyaraj, S; Saravanan, M

2013-08-01

143

Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation  

PubMed Central

Characterizing novel drugs and chemical probes of biological systems is hindered by difficulties in identifying the mechanism of action (MOA) of biologically active molecules. Here we present a metabolite suppression approach to explore the MOA of antibacterial compounds under nutrient restriction. We assembled an array of metabolites that can be screened for suppressors of inhibitory molecules. Further, we identified inhibitors of E. coli growth under nutrient limitation and charted their interactions with our metabolite array. This strategy led to the discovery and characterization of three novel antibacterial compounds, MAC168425, MAC173979 and MAC13772. We showed that MAC168425 interferes with glycine metabolism, MAC173979 is a time-dependent inhibitor of p-aminobenzoic acid biosynthesis and MAC13772 inhibits biotin biosynthesis. We conclude that metabolite suppression profiling is an effective approach to focus MOA studies on compounds impairing metabolic capabilities. Such bioactives can serve as chemical probes of bacterial physiology and as leads for antibacterial drug development. PMID:24121552

Zlitni, S.; Ferruccio, L.F.

2014-01-01

144

A rapid CE-potential gradient detection method for determination of quinolones.  

PubMed

A rapid CE coupled with potential gradient detection (PGD) for the separation and detection of four quinolones, namely, enoxacin, ofloxacin (OFL), fleroxacin, and pazufloxacin, was described. Separation was performed in a fused-silica capillary (75 microm x 8.5 cm) using a buffer of 30 mM Tris and 4 mM phosphoric acid at pH 8.9. Under the separation voltage of 3 kV, the quinolones were separated within 2.8 min with good linearity (r(2) >or= 0.985). The method was successfully applied in determining OFL in a pharmaceutical formulation. Also, a liquid-liquid extraction (LLE) method was developed and coupled to CE-PGD in determining quinolones that spiked in milk samples. With dichloromethane and hexane for enrichment and purification, the LLE recoveries of the four quinolones were in the range of 77-106%. The detection limits of the quinolones with LLE-CE-PGD were from 23 to 65 ng/mL. The proposed CE-PGD method was validated with an HPLC method, and the results indicated consistency between the two methods. PMID:17941113

Fan, Yongxia; Gan, Xiao; Li, Shuo; Qin, Weidong

2007-11-01

145

The evidence for clonal spreading of quinolone resistance with a particular clonal complex of Campylobacter jejuni.  

PubMed

SUMMARY Campylobacter is the most prevalent cause of bacterial gastroenteritis worldwide and it represents a significant public health risk of increasing severity due to its escalating resistance to clinically important quinolone and macrolide antibiotics. As a zoonotic pathogen Campylobacter is transmitted along the food chain and naturally cycles from environmental waters, feedstuff, animals and food to humans. We determined antibiotic resistance profiles, as well as multilocus sequence types and flaA-SVR types for 52 C. jejuni isolated in Slovenia from human, animal, raw and cured chicken meat and water samples. Twenty-eight different sequence types, arranged in ten clonal complexes, three new allele types and five new sequence types were identified, indicating the relatively high diversity in a small group of strains. The assignment of strains from different sources to the same clonal complexes indicates their transmission along the food supply chain. The most prevalent clonal complex was CC21, which was also the genetic group with 95% of quinolone-resistant strains. Based on the genetic relatedness of these quinolone-resistant strains identified by polymerase chain reaction with a mismatch amplification mutation assay and sequencing of the quinolone resistance-determining region of the gyrA gene, we conclude that the high resistance prevalence observed indicates the local clonal spread of quinolone resistance with CC21. PMID:24534165

Kova?, J; Cadež, N; Lušicky, M; Nielsen, E Møller; Ocepek, M; Raspor, P; Možina, S Smole

2014-12-01

146

Screening for antibacterial activity in 72 species of wood-colonizing fungi by the Vibrio fisheri bioluminescence method.  

PubMed

Resistance of pathogenic bacteria to antibiotics leads scientists to discover new antibacterial drugs. Ninety samples of wood-colonizing fungi were cultivated on agar plates, and their extracts tested for antibacterial activity using the Vibrio fischeri bioluminescence test. Two fungi species, Serpula lacrymans and Nectria vilior, were found to be a potential new source of thermostable antibiotics. Vibrio fischeri bioluminescence test was found to be a useful method for antibacterial activity screening from the samples of natural origin. PMID:15378528

Zrimec, Maja Berden; Zrimec, Alexis; Slanc, Petra; Kac, Javor; Kreft, Samo

2004-01-01

147

Antibacterially active substances  

Microsoft Academic Search

Synthesis of two hydroxy-derivatives of nalidixic acid as a result of microbial transformation was demonstrated in certain\\u000a species of the genusAspergillus. Aspergillus alliaceus produced 7-hydroxy-nalidixic acid andAspergillus niger 6-hydroxy-nalidixic acid. It was demonstrated that the antibacterial activity of both hydroxy-derivatives (tested inEscherichia coli) was lower than that of the initial nalidixis acid.

A. ?apek; A. Šimek; E. Svátek; M. Bud?šínský

1969-01-01

148

The qualitative and quantitative determination of quinolones of first and second generation by capillary electrophoresis.  

PubMed

Capillary electrophoresis (CE) was applied to the study of 10 quinolones of first and second generation--nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, fleroxacin, and flumequine. Separation was performed on a fused silica capillary (75 microm-60 cm) using a phosphate buffer (pH 7.0, 125 mM). Detection was at 214 nm. Only norfloxacin and ciprofloxacin cannot be separated in this way. Because of the specificity of the method, the identification of the individual quinolones by their migration time was possible. The same system has been applied for the quantitative determination of quinolones in tablets and capsules. Excipients do not adversely affect the results. Some parameters (linearity, precision, accuracy) were validated. Especially the possibility of simultaneous quantification and identification of the active ingredient in the finished product is very attractive. PMID:10815719

Fierens, C; Hillaert, S; Van den Bossche, W

2000-06-01

149

Development of 1-hydroxy-2(1H)-quinolone-based photoacid generators and photoresponsive polymer surfaces.  

PubMed

A new class of carboxylate and sulfonate esters of 1-hydroxy-2(1H)-quinolone has been demonstrated as nonionic photoacid generators (PAGs). Irradiation of carboxylates and sulfonates of 1-hydroxy-2(1H)-quinolone by UV light (??310?nm) resulted in homolysis of weak N-O bond leading to efficient generation of carboxylic and sulfonic acids, respectively. The mechanism for the homolytic N-O bond cleavage was supported by time-dependent DFT calculations. Photoresponsive 1-(p-styrenesulfonyloxy)-2-quinolone-methyl methacrylate (SSQL-MMA) and 1-(p-styrenesulfonyloxy)-2-quinolone-lauryl acrylate (SSQL-LA) copolymers were synthesized from PAG monomer 1-(p-styrenesulfonyloxy)-2-quinolone, and subsequently controlled surface wettability was demonstrated for the above-mentioned photoresponsive polymers. PMID:22887636

Ikbal, Mohammed; Banerjee, Rakesh; Atta, Sanghamitra; Jana, Avijit; Dhara, Dibakar; Anoop, Anakuthil; Singh, N D Pradeep

2012-09-17

150

Drugs  

Microsoft Academic Search

Reviews 11 studies, published from the year 1917 to 1910, by Miles, Fiske, Graham, Rowe, Anderson, Marks, Stanley, Johnson, Macht, Isaacs, Greenberg and Lashley on the effects of alcohol, tobacco smoking, drug addiction, addiction to medicines like aspirin, and strychnine and caffeine.

A. T. Poffenberger

1919-01-01

151

Genotoxic potential of quinolone antimicrobials in the in vitro comet assay and micronucleus test.  

PubMed

The purpose of this study was to examine the genotoxicity of quinolone antimicrobials. We investigated the genotoxic potential of eight quinolones, namely nalidixic acid (NA), pipemidic acid (PPA), oxolinic acid (OA), piromidic acid (PA), enoxacin (ENX), ofloxacin (OFLX), norfloxacin (NFLX) and ciprofloxacin (CPFX), by the in vitro alkaline single-cell gel electrophoresis (comet) assay at pH>13. WTK-1 cells (mutant p53) were treated with each of the eight quinolones at 62.5-1000 microg/mL for 2, 4 and 20 h. NFLX and CPFX significantly induced DNA damage concentration-dependently after 4 and 20 h treatment, but this damage was recoverable. On the other hand, DNA was not damaged in the cells treated with six other quinolones. In the cells treated with NFLX and CPFX for 20 h, DNA migration was compared by the comet assay at pH 10, 12.1 and >13. The comet assay both at pH 12.1 and >13 showed increased DNA migration, but there was no positive response in the comet assay at pH 10. In the in vitro micronucleus (MN) test, WTK-1 cells were treated with each of four quinolones (NA, PPA, NFLX and CPFX) at 15.63-125 microg/mL for 20 h. NFLX significantly increased MNs in the cells, but no changes were noted in the cells treated with three other quinolones. These results suggest that NFLX and CPFX induced DNA single strand breaks (SSBs), and that NFLX-induced SSBs resulted in chromosome aberrations. PMID:16384725

Itoh, Tadashi; Mitsumori, Kunitoshi; Kawaguchi, Satomi; Sasaki, Yu F

2006-02-28

152

Prevalence of plasmid-mediated quinolone resistance determinants among oxyiminocephalosporin-resistant Enterobacteriaceae in Argentina  

PubMed Central

High quinolone resistance rates were observed among oxyiminocephalosporin-resistant enterobacteria. In the present study, we searched for the prevalence of plasmid-mediated quinolone resistance (PMQR) genes within the 55 oxyiminocephalosporin-resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6')-Ib-cr and qnrB, which had prevalence rates of 42.4% and 33.3%, respectively. The aac(6')-Ib-cr gene was more frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously distributed among all CTX-M producers. PMID:24037111

Cruz, Giovanna Rincon; Radice, Marcela; Sennati, Samantha; Pallecchi, Lucia; Rossolini, Gian María; Gutkind, Gabriel; Conza, Jose Alejandro Di

2013-01-01

153

Drug interactions with antiviral drugs.  

PubMed

Antiviral drug interactions are a particular problem among immuno-compromised patients because these patients are often receiving multiple different drugs, i.e. antiretroviral drugs and drugs effective against herpesvirus. The combination of zidovudine and other antiretroviral drugs with different adverse event profiles, such as didanosine, zalcitabine and lamivudine, appears to be well tolerated and no relevant pharmacokinetic interactions have been detected. The adverse effects of didanosine and zalcitabine (i.e. peripheral neuropathy and pancreatitis) should be taken into account when administering these drugs with other drugs with the same tolerability profile. Coadministration of zidovudine and ganciclovir should be avoided because of the high rate of haematological intolerance. In contrast, zidovudine and foscarnet have synergistic effect and no pharmacokinetic interaction has been detected. No major change in zidovudine pharmacokinetics was seen when the drug was combined with aciclovir, famciclovir or interferons. However, concomitant use of zidovudine and ribavirin is not advised. Although no pharmacokinetic interaction was documented when didanosine was first administered with intravenous ganciclovir, recent studies have shown that concentration of didanosine are increased by 50% or more when coadministered with intravenous or oral ganciclovir. The mechanism of this interaction has not been elucidated. Lack of pharmacokinetic interaction was demonstrated between foscarnet and didanosine or ganciclovir. Clinical trials have shown that zidovudine can be administered safely with paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, oxazepam or codeine. Inhibition of zidovudine glucuronidation has been demonstrated with fluconazole, atovaquone, valproic acid (valproate sodium), methadone, probenecid and inosine pranobex; however, the clinical consequences of this have not been fully investigated. No interaction has been demonstrated with didanosine per se but care should be taken of interaction with the high pH buffer included in the tablet formulation. Drugs that need an acidic pH for absorption (ketoconazole, itraconazole but not fluconazole, dapsone, pyrimethamine) or those that can be chelated by the ions of the buffer (quinolones and tetracyclines) should be administered 2 hours before or 6 hours after didanosine. Very few interaction studies have been undertaken with other antiviral drugs. Coadministration of zalcitabine with the antacid 'Maalox' results in a reduction of its absorption. Dapsone does not influence the disposition of zalcitabine. Cotrimoxazole (trimethoprim-sulfamethoxazole) causes an increase in lamivudine concentrations by 43%. Saquinavir, delavirdine and atevirdine appeared to be metabolised by cytochrome P450 and interactions with enzyme inducers or inhibitors could be anticipated. Some studies showed that interferons can reduce drug metabolism but only a few studies have evaluated the pathways involved. Further studies are required to better understand the clinical consequences of drug interactions with antiviral drugs. Drug-drug interactions should be considered in addition to individual drug clinical benefits and safety profiles. PMID:8743337

Taburet, A M; Singlas, E

1996-05-01

154

Characterization of Selective Antibacterial Peptides by Polarity Index  

PubMed Central

In the recent decades, antibacterial peptides have occupied a strategic position for pharmaceutical drug applications and became subject of intense research activities since they are used to strengthen the immune system of all living organisms by protecting them from pathogenic bacteria. This work proposes a simple and easy statistical/computational method through a peptide polarity index measure by which an antibacterial peptide subgroup can be efficiently identified, that is, characterized by a high toxicity to bacterial membranes but presents a low toxicity to mammal cells. These peptides also have the feature not to adopt to an alpha-helicoidal structure in aqueous solution. The double-blind test carried out to the whole Antimicrobial Peptide Database (November 2011) showed an accuracy of 90% applying the polarity index method for the identification of such antibacterial peptide groups. PMID:22611416

Polanco, C.; Samaniego, J. L.; Buhse, T.; Mosqueira, F. G.; Negron-Mendoza, A.; Ramos-Bernal, S.; Castanon-Gonzalez, J. A.

2012-01-01

155

Looking for new targets: simple coumarins as antibacterial agents.  

PubMed

The dramatic worldwide increase of dangerous infections by resistant and multi-resistant microbes makes the search of new molecules and new chemical entities an important topic in Medicinal Chemistry. As the ideal drug candidate has not been attained, an intensive search for new and innovative antimicrobials is still needed. A small series of 3-amino/nitrocoumarins without substitutions or substituted by methyl or methoxy groups at different positions were synthesized and evaluated for their antibacterial and antifungal activities against clinical isolates of Staphylococcus aureus, Escherichia coli and Candida albicans strains. Some of these structurally simple molecules exhibited antibacterial activity. The preliminary SAR study showed that the antibacterial activity against E. coli and S. aureus was dependent on the kind and position of the substitution pattern at the coumarin moiety. PMID:22779756

Matos, Maria João; Vazquez-Rodriguez, Saleta; Santana, Lourdes; Uriarte, Eugenio; Fuentes-Edfuf, Cristina; Santos, Ysabel; Muñoz-Crego, Angeles

2012-11-01

156

Synthesis, molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents.  

PubMed

Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of novel metronidazole derivatives were designed and synthesized based on nitroimidazole scaffold in order to find some more potent antibacterial drugs. For these compounds which were reported for the first time, their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-positive strains. Compound 4m represented the most potent antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 ?g/mL and it showed the most potent activity against S. aureus TyrRS with IC50 of 0.0024 ?M. Molecular docking of 4m into S. aureus tyrosyl-tRNA synthetase active site were also performed to determine the probable binding mode. PMID:24680059

Wang, She-Feng; Yin, Yong; Qiao, Fang; Wu, Xun; Sha, Shao; Zhang, Li; Zhu, Hai-Liang

2014-04-15

157

Novel Antibacterial Nanofibrous PLLA Scaffolds  

PubMed Central

In order to achieve high local bioactivity and low systemic side effects of antibiotics in the treatment of dental, periodontal and bone infections, a localized and temporally controlled delivery system is crucial. In this study, a three-dimensional (3D) porous tissue engineering scaffold was developed with the ability to release antibiotics in a controlled fashion for long-term inhibition of bacterial growth. The highly soluble antibiotic drug, Doxycycline (DOXY), was successfully incorporated into PLGA nanospheres using a modified water-in-oil-in-oil (w/o/o) emulsion method. The PLGA nanospheres (NS) were then incorporated into prefabricated nanofibrous PLLA scaffolds with a well interconnected macroporous structure. The release kinetics of DOXY from four different PLGA NS formulations on a PLLA scaffold was investigated. DOXY could be released from the NS-scaffolds in a locally and temporally controlled manner. The DOXY release is controlled by DOXY diffusion out of the NS and is strongly dependent upon the physical and chemical properties of the PLGA. While PLGA50-6.5K, PLGA50-64K, and PLGA75-113K NS-scaffolds discharge DOXY rapidly with a high initial burst release, PLGA85-142K NS-scaffold can extend the release of DOXY to longer than 6 weeks with a low initial burst release. Compared to NS alone, the NS incorporated on a 3-D scaffold had significantly reduced the initial burst release. In vitro antibacterial tests of PLGA85 NS-scaffold demonstrated its ability to inhibit common bacterial growth (S.aureus and E.coli) for a prolonged duration. The successful incorporation of DOXY onto 3-D scaffolds and its controlled release from scaffolds extends the usage of nano-fibrous scaffolds from the delivery of large molecules such as growth factors to the delivery of small hydrophilic drugs, allowing for a broader application and a more complex tissue engineering strategy. PMID:20570700

Feng, Kai; Sun, Hongli; Bradley, Mark A.; Dupler, Ellen J.; Giannobile, William V.; Ma, Peter X.

2010-01-01

158

Mini-Review Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa  

E-print Network

Mini-Review Parallel evolution and local differentiation in quinolone resistance in Pseudomonas of antibiotic resistance in pathogens is a major impediment to the control of microbial disease. Here, we review the therapeutic implications of local differentiation in resistance mechanisms to a common antibiotic

Kassen, Rees

159

CE determination of quinolones in the presence of bovine serum albumin.  

PubMed

This article describes the influence of bovine serum albumin (BSA) as an additive on the capillary electrophoresis-potential gradient determination of five quinolones, enoxacin, norfloxacin, ofloxacin, fleroxacin, and pazufloxacin. With 10 mg/L of BSA present in the buffer of 30 mM Tris and 3 mM phosphoric acid at pH 9, the detection limits of the five quinolones were in the range of 0.24-0.68 mg/L, i. e. 5.8-16.5-fold lower than those obtained with the buffer devoid of BSA, and the analysis time was shortened. We suggest that the inner wall-adsorbed BSA suppresses the adsorption of quinolones and simultaneously enhances the electroosmotic flow rate. Our experiments indicated that adopting the potential gradient detection technique could eliminate the interference of the UV-active proteins on the detection of quinolones that would occur with conventional optical detection, and therefore offer high detection sensitivity. As a demonstration, the method was applied to the determination of QNs in fortified chicken muscle sample with satisfactory results. PMID:19035388

Qin, Weidong; Liu, Qingchun; Fan, Yongxia

2009-01-01

160

Identification, biological activity, and mechanism of the anti-ischemic quinolone analog  

E-print Network

Identification, biological activity, and mechanism of the anti-ischemic quinolone analog Chan, cells are often endangered in a circumstance of oxidative stress, which results in further tissue injury and furthermore considerably reduced infarct volume size in in vivo rat focal cerebral ischemic animal model (MCAO

Suh, Young-Ger

161

Prevalence and characterization of quinolone resistance in Laribacter hongkongensis from grass carp and Chinese tiger frog.  

PubMed

Laribacter hongkongensis is a food-borne bacterium associated with community-acquired gastroenteritis and diarrhoea. Quinolone resistance was recently reported in bacterial isolates from aquatic products, but the molecular mechanisms for resistance were still unknown. In this study, a total of 157 L. hongkongensis strains were isolated from grass carps (n = 443) and Chinese tiger frogs (n = 171). Twenty-one ciprofloxacin-resistant strains were analysed for mutations in quinolone resistance-determining regions (QRDR), acquired quinolone resistance (AQR) genes and the role of efflux pumps in resistance. All QRDR mutations in gyrA (codons 85 and 89) and parC (codons 83 and 231) were found to be closely associated with ciprofloxacin resistance. The AQR gene aac(6')-Ib-cr was found in 42.9% (9/21) of the resistant strains, but qnrA, qnrB, qnrC, qnrD, qnrS and qepA were not detected. No significant change of MICs to ciprofloxacin was observed in the presence of an efflux pump inhibitor, indicating the role of efflux pump was probably absent. All 21 ciprofloxacin-resistant strains showed different electrophoretic patterns, which suggested they were not genetically related. These data highlight the importance of QRDR mutations and the AQR gene aac(6')-Ib-cr during the development of quinolone resistance in a heterogeneous population of L. hongkongensis. PMID:23906590

Chen, Ding-Qiang; Yang, Ling; Luo, Yu-Ting; Mao, Min-Jie; Lin, Yong-Ping; Wu, Ai-Wu

2013-10-01

162

In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.  

PubMed

We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants. PMID:15135497

Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-05-01

163

A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties  

SciTech Connect

Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]{center_dot}H{sub 2}O (1), [M(norfH)(bpdc)]{center_dot}H{sub 2}O (M=Cd (2) and Mn (3)), [Mn{sub 2}(cfH)(odpa)(H{sub 2}O){sub 3}]{center_dot}0.5H{sub 2}O (4), [Co{sub 2}(norfH)(bpta)({mu}{sub 2}-H{sub 2}O)(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O (5) and [Co{sub 3}(saraH){sub 2}(Hbpta){sub 2}(H{sub 2}O){sub 4}]{center_dot}9H{sub 2}O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4 Prime -biphenyldicarboxylate, odpa=4,4 Prime -oxydiphthalate, bpta=3,3 Prime ,4,4 Prime -biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed. - Graphical abstract: Six novel 2D metal-quinolone complexes have been prepared by self-assemblies of the quinolones and metal salts in the presence of long aromatic polycarboxylates. Highlights: Black-Right-Pointing-Pointer Compounds 1-3 consist of novel 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Black-Right-Pointing-Pointer Compounds 4 and 5 are two novel 2D layers based on tetranuclear Mn or Co clusters with kgd topology. Black-Right-Pointing-Pointer Compound 6 is the first example of metal-quinolone complexes with 2D bilayer structure. Black-Right-Pointing-Pointer Compounds 1-6 represent six unusual examples of 2D metal-quinolone complexes.

He, Jiang-Hong [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)] [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Xiao, Dong-Rong, E-mail: xiaodr98@yahoo.com.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)] [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)] [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Luo, Qun-Li, E-mail: qlluo@swu.edu.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)] [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Wang, En-Bo, E-mail: wangeb889@nenu.edu.cn [Key Laboratory of Polyoxometalate Science of Ministry of Education, Department of Chemistry, Northeast Normal University, Changchun 130024 (China)] [Key Laboratory of Polyoxometalate Science of Ministry of Education, Department of Chemistry, Northeast Normal University, Changchun 130024 (China)

2013-02-15

164

Decay mechanisms of protonated 4-quinolone antibiotics after electrospray ionization and ion activation.  

PubMed

This study presents a detailed experimental investigation of charge isomers of protonated 4-quinolone antibiotics molecules formed during electrospray ionization (ESI) with proposed dissociation mechanisms after collisional activation. Piperazinyl quinolones have been previously shown to exhibit erratic behavior during tandem MS analyses of biological samples, which originated from varying ratios of two isomeric variants formed during ESI. Here, a combination of ESI-collision-induced dissociation (CID), differential ion mobility spectrometry (DMS), high resolution MS, and density functional theory (DFT) was used to investigate the underlying mechanisms of isomer formation and their individual dissociation behaviors. The study focused on ciprofloxacin; major findings were confirmed using structurally related 4-quinolones. DFT calculations showed a reversal of basicity for piperazinyl quinolones between liquid and gas phase. We provide an experimental comparison and theoretical treatment of factors influencing the formation ratio of the charge isomers during ESI, including solvent pH, protic/aprotic nature of solvent, and structural effects such as pK a and proton affinity. The actual dissociation mechanisms of the isomers of the protonated molecules were studied by separating the individual isomers via DMS-MS, which allowed type-specific CID spectra to be recorded. Both primary CID reactions of the two charge isomers originated from the same carboxyl group by charge-remote (CO2 loss) and charge-mediated (H2O loss) fragmentation of the piperazinyl quinolones, depending on whether the proton resides on the more basic keto or the piperazinyl group, followed by a number of secondary dissociation reactions. The proposed mechanisms were supported by calculated energies of precursors, transition states, and products for competing pathways. PMID:25201456

Kova?evi?, Borislav; Schorr, Pascal; Qi, Yulin; Volmer, Dietrich A

2014-11-01

165

Antibacterial efficacy of acridine derivatives conjugated with gold nanoparticles.  

PubMed

Adsorption of acridine derivatives viz. 9-aminoacridine hydrochloride hydrate (9AA-HCl), acridine yellow (AY), acridine orange (AO), and proflavine (Pro) on citrate stabilized gold nanoparticle surface were studied using different analytical techniques like UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The amine moiety of acridine derivative binds strongly to the gold nanoparticles as confirmed by spectroscopic studies. The plasmon band observed for the wine red colloidal gold at 525 nm in the UV-vis spectrum is characteristic of gold nanoparticles. However, with the addition of acridine derivatives the intensity of the absorption band at 525 nm decreases and a new peak emerges at red-end region - a signature of formation of gold-drug complex. The TEM images show the average size of citrate stabilized gold nanoparticles as 15-20 nm, which becomes larger in the presence of various drugs due to aggregation. From the thermogravimetric analyses (TGA) we have measured the number of drug molecules attached per gold nanoparticle (AuNP). These gold nanoparticles are very important as drug delivery vehicles and for clinical applications it is necessary to understand their activity in vivo. The antibacterial efficacy of drugs coated gold nanoparticles were studied against various strains of Gram positive and Gram negative bacteria. Among the four drugs, 9AA-HCl and AO showed antibacterial activity and for both of them the AuNP conjugated drug showed better antibacterial efficacy than the bare drug. Because of the high penetrating power and large surface area of Au(0), a single gold nanoparticle can adsorb multiple drug molecules, hence this total entity acts as a single group against the bacteria. PMID:25087507

Mitra, Piyali; Chakraborty, Prabal Kumar; Saha, Partha; Ray, Pulak; Basu, Samita

2014-10-01

166

Review article Epidemiology of resistance to quinolones in Salmonella  

E-print Network

prescriptions in human medicine worldwide and represent the drug of choice for the treatment of a wide range, namely typhoid fever and gas- troenteritis. Typhoid fever is a generalised infection with severe symptoms

Paris-Sud XI, Université de

167

Antibacterial diterpenoids from Cedrus atlantica  

Microsoft Academic Search

Four diterpene alcohols were isolated from the neutral hexane extract of the cones of Cedrus atlantica, and their structures were confirmed after comparing their spectral data with literature values. These products exhibited significant antibacterial activity against gram (±) bacteria.

M. Dakir; F. El Hanbali; F. Mellouki; M. Akssira; A. Benharref; J. F. QuIlez del Moral; A. F. Barrero

2005-01-01

168

Antibacterial diterpenoids from Cedrus atlantica.  

PubMed

Four diterpene alcohols were isolated from the neutral hexane extract of the cones of Cedrus atlantica, and their structures were confirmed after comparing their spectral data with literature values. These products exhibited significant antibacterial activity against gram (+/-) bacteria. PMID:16076643

Dakir, M; El Hanbali, F; Mellouki, F; Akssira, M; Benharref, A; Quilez Del Moral, J F; Barrero, A F

2005-10-01

169

[Antibiotic susceptibility of blood-borne Streptococcus pneumoniae and efficacy assessment of respiratory quinolones using Monte Carlo simulation].  

PubMed

We analyzed Streptococcus pneumoniae isolates from the bloodstream between April 2005 and February 2007. We analyzed isolates of 28 strains from medical facilities in Gifu prefecture to determine antibiotic susceptibility, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes. We also assessed the efficacy of respiratory quinolones using Monte Carlo simulation. Garenoxacin (GRNX) and moxifloxacin (MFLX) showed the lowest MIC90 value of 0.125 microg/mL, followed by MIC90 of imipenem (IPM) of 0.25 microg/mL and tosufloxacin (TFLX), MIC90 of meropenem (MEPM) and vancomycin (VCM) of 0.5 microg/mL. Twenty-two strains possessed at least one mutation in PBP-encoding genes pbp1a, pbp2x or pbp2b and seven strains possessed all three mutant alleles. Twenty-two strains possessed either of macrolide resistant genes ermB or mefA, and one strain possessed both. On efficacy assessment, we calculated the probability of target attainment for free-drug area under the curve (fAUC)/MIC ratio (fAUC/MIC). GRNX and MFLX showed a probability of 90% or more at fAUC/MIC of 30 and 125, each considered effective against Gram-positive bacteria and suppression of resistance development, furthermore, GRNX showed a probability of 89.7% at fAUC/MIC of 250. PMID:20836402

Kawamoto, Hiroshi; Nomura, Nobuhiko; Mitsuyama, Junichi; Yamaoka, Kazukiyo; Asano, Yuko; Sawamura, Haruki; Suematsu, Hiroyuki; Teraji, Mayumi; Hashido, Hikonori; Matsukawa, Yoko; Matsubara, Shigenori; Miyabe, Takanori; Mikamo, Hiroshige; Watanabe, Kunitomo

2010-02-01

170

Structure of PqsD, a Pseudomonas Quinolone Signal Biosynthetic Enzyme, in Complex with Anthranilate†  

PubMed Central

Pseudomonas quinolone signal (PQS), 2-heptyl-3-hydroxy-4-quinolone, is an intercellular alkyl quinolone signaling molecule produced by the opportunistic pathogen Pseudomonas aeruginosa. Alkyl quinolone signaling is an atypical system that, in P. aeruginosa, controls the expression of numerous virulence factors. PQS is synthesized from the tryptophan pathway intermediate, anthranilate, which is either derived from the kynurenine pathway or from an alkyl quinolone specific anthranilate synthase encoded by phnAB. Anthranilate is converted to PQS by the enzymes encoded by the pqsABCDE operon and pqsH. PqsA forms an activated anthraniloyl-CoA thioester that shuttles anthranilate to the PqsD active site where it is transferred to Cys112 of PqsD. In the only biochemically characterized reaction, a condensation then occurs between anthraniloyl-PqsD and malonyl-CoA or malonyl-ACP, a second PqsD substrate, forming 2,4-dihydroxyquinoline (DHQ). The role PqsD plays in the biosynthesis of other alkyl quinolones, such as PQS, is unclear though it has been reported to be required for their production. No evidence however, exists that DHQ is a PQS precursor. Here we present a structural and biophysical characterization of PqsD that includes several crystal structures of the enzyme including that of the PqsD-anthranilate covalent intermediate and the inactive Cys112Ala active site mutant in complex with anthranilate. The structure reveals that PqsD is structurally similar to the FabH and chalcone synthase families of fatty acid and polyketide synthases. The crystallographic asymmetric unit contains a PqsD dimer. The PqsD monomer is composed of two nearly identical ~170 residue ????? domains. The structures show anthranilate-liganded Cys112 is positioned deep in the protein interior at the bottom of a ~15 Å long channel while a second anthraniloyl-CoA molecule is waiting in the cleft leading to the protein surface. Cys112, His257, and Asn287 form the FabH-like catalytic triad of PqsD. The C112A mutant is inactive although it still reversibly binds anthraniloyl-CoA. The covalent complex between anthranilate and Cys112 clearly illuminates the orientation of key elements of the PqsD catalytic machinery and represents a snapshot of a key point in the catalytic cycle. PMID:19694421

Bera, Asim K.; Atanasova, Vesna; Robinson, Howard; Eisenstein, Edward; Coleman, James P.; Pesci, Everett C.; Parsons, James F.

2009-01-01

171

Controlled release of antibiotics encapsulated in the electrospinning polylactide nanofibrous scaffold and their antibacterial and biocompatible properties  

NASA Astrophysics Data System (ADS)

In this research, the drug loaded polylactide nanofibers are fabricated by electrospinning. Morphology, microstructure and mechanical properties are characterized. Properties and mechanism of the controlled release of the nanofibers are investigated. The results show that the drug loaded polylactide nanofibers do not show dispersed phase, and there is a good compatibility between polylactide and drugs. FTIR spectra show that drugs are encapsulated inside the polylactide nanofibers, and drugs do not break the structure of polylcatide. Flexibility of drug loaded polylactide scaffolds is higher than that of the pure polylactide nanofibers. Release rate of the drug loaded nanofibers is significantly slower than that of the drug powder. Release rate increases with the increase of the drugs’ concentration. The research mechanism suggests a typical diffusion-controlled release of the three loaded drugs. Antibacterial and cell culture show that drug loaded nanofibers possess effective antibacterial activity and biocompatible properties.

Wang, Shu-Dong; Zhang, Sheng-Zhong; Liu, Hua; Zhang, You-Zhu

2014-04-01

172

Molecular epidemiological survey on quinolone resistance genotype and phenotype of Escherichia coli in septicemic broilers in Hebei, China.  

PubMed

In this study, the quinolone-resistant determining region (QRDR) of gyrA of Escherichia coli and plasmid-mediated quinolone resistance (PMQR) genes, qnr(qnrA, qnrB, and qnrS), and aac(6?')-Ib-cr were detected, sequenced, and analyzed. In addition, antimicrobial susceptibility tests (using the Kirby-Bauer disc diffusion method) were performed for all 111 E. coli isolates from septicemic broilers in Hebei, China. The results show that the resistance rates were as follows: ofloxacin 99.10%, ciprofloxacin 93.69%, levofloxacin 91.89%, norfloxacin 90.09%, and gatifloxacin 76.58%. Of the PMQR genes examined, aac(6?')-Ib-cr (36.04%) was the most frequently identified gene in all isolates, followed by qnrS (8.11%), qnrB (0.90%), and qnrA (0%). Of the QRDR examined in the 40 phenotypic quinolone-resistant isolates, compared with the gyrA(+) gene of E. coli K-12, 4 amino acid exchanges were found, namely Ser-83?Asp, Asp-87?Asn, Asp-87?Tyr, and Asp-87?Ala, and all 40 isolates had 1 or 2 exchanges in QRDR. It was concluded that quinolone-resistance in E. coli remains a serious problem in Hebei, China. Therefore, there is considerable local surveillance of quinolone resistance. Plasmid-mediated quinolone resistance of the qnr type remains rare in Hebei, China, and mutation in QRDR may be the main problem. PMID:24570454

Xie, Rong; Huo, Shuying; Li, Yurong; Chen, Ligong; Zhang, Feiyan; Wu, Xianjun

2014-02-01

173

Plasmid-related quinolone resistance determinants in epidemic Vibrio parahaemolyticus, uropathogenic Escherichia coli, and marine bacteria from an aquaculture area in Chile.  

PubMed

Marine bacteria from aquaculture areas with industrial use of quinolones have the potential to pass quinolone resistance genes to animal and human pathogens. The VPA0095 gene, related to the quinolone resistance determinant qnrA, from clinical isolates of epidemic Vibrio parahaemolyticus conferred reduced susceptibility to quinolone after cloning into Escherichia coli K-12 either when acting alone or synergistically with DNA gyrase mutations. In addition, a plasmid-mediated quinolone resistance gene from marine bacteria, aac(6')-Ib-cr, was identical to aac(6')-Ib-cr from urinary tract isolates of E. coli, suggesting a recent flow of this gene between these bacteria isolated from different environments. aac(6')-Ib-cr from E. coli also conferred reduced susceptibility to quinolone and kanamycin when cloned into E. coli K-12. PMID:24760167

Aedo, Sandra; Ivanova, Larisa; Tomova, Alexandra; Cabello, Felipe C

2014-08-01

174

In Vitro Activities of Three Nonfluorinated Quinolones against Representative Bacterial Isolates  

PubMed Central

In vitro susceptibility tests were performed to document the inhibitory activities of three nonfluorinated quinolone (NFQ) compounds (PGE 9262932, PGE 9509924, and PGE 4175997) compared to those of ciprofloxacin, levofloxacin, and trovafloxacin against 3,030 bacterial isolates. The spectra of the NFQ agents included most gram-positive species as well as quinolone-susceptible Enterobacteriaceae. Ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus strains were inhibited by the NFQ series at ?1.0 ?g/ml. The NFQ compounds were not very active against Pseudomonas aeruginosa and most other nonfermentative gram-negative bacilli. Against other species, the potency of the NFQ agents was similar to that of trovafloxacin. Continued investigation of the NFQ compounds seems to be warranted. PMID:11353655

Barry, Arthur L.; Fuchs, Peter C.; Brown, Steven D.

2001-01-01

175

Synthesis and antiproliferative activity of quinolone nucleosides against the human myelogenous leukemia k-562 cell line.  

PubMed

A set of 6-substituted quinolone nucleosides linked to aniline or phenol via N or O heteroatom-bridges presenting new compounds were synthesized by palladium-catalyzed Buchwald-Hartwig cross-coupling reactions. 6-Bromoquinolone nucleoside precursors, being protected by either benzoyl or TBDMS protecting groups on the ribose moiety, were subjected to different Buchwald-Hartwig conditions as the key step. Defined deprotection steps led, in good yields, to the final target compounds that carry, in position 3, either ester, acid, or amide functions. Thus, a series of novel quinolone nucleoside derivatives was obtained via a convergent synthesis route. Biological tests in human chronic myelogenous leukemia K562 cells exerted an efficient antiproliferative activity for two of them without induction of differentiation. These novel nucleosides deserve further experiments to determine their antiproliferative effects on other CML cell lines. PMID:24105761

Wicke, Lena; Engels, Joachim W; Gambari, Roberto; Saab, Antoine M

2013-10-01

176

76 FR 59406 - Anti-Infective Drugs Advisory Committee; Notice of Meeting  

Federal Register 2010, 2011, 2012, 2013

...of antibacterials for the treatment of community-acquired bacterial pneumonia and the draft document entitled ``Guidance for Industry: Community-Acquired Bacterial Pneumonia: Developing Drugs for...

2011-09-26

177

In Vitro Activities of Gatifloxacin, Two Other Quinolones, and Five Nonquinolone Antimicrobials against Obligately Anaerobic Bacteria  

PubMed Central

The activity of the new fluoroquinolone gatifloxacin was compared with those of other quinolones and antimicrobial agents of other classes against 294 anaerobes by the broth microdilution technique. For all strains tested, gatifloxacin MICs at which 50 and 90% of the isolates were inhibited were 0.5 and 2 mg/liter, respectively, and were 3 to 4 dilution steps lower than, e.g., ciprofloxacin. PMID:10543764

Schaumann, Reiner; Ackermann, Grit; Pless, Baerbel; Claros, Marina C.; Rodloff, Arne C.

1999-01-01

178

The comparative pharmacokinetics and tissue penetration of four quinolones including intravenously administered enoxacin  

Microsoft Academic Search

Summary The pharmacokinetics and tissue penetration of four quinolones were studied. The compounds were norfloxacin (400 mg p.o.), enoxacin (600 mg p.o. and 400 mg i.v.), ciprofloxacin (100 mg i.v. and 500 mg p.o.) and ofloxacin (600 mg p.o.) given to healthy volunteers. Of the oral agents studied ofloxacin and ciprofloxacin were the most rapidly absorbed (Tmax 1.2 h) and

R. Wise; D. Lister; C. A. M. McNulty; D. Griggs; J. M. Andrews

1986-01-01

179

Plasmid-mediated Quinolone Resistance among Non-TyphiSalmonella enterica Isolates, USA  

PubMed Central

We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella spp. isolated from humans, food animals, and retail meat in the United States in 2007. Six isolates collected from humans harbored aac(6?)Ib-cr or a qnr gene. Most prevalent was qnrS1. No animal or retail meat isolates harbored a plasmid-mediated mechanism. PMID:21029547

Howie, Rebecca; Rickert, Regan; Krueger, Amy; Tran, Thu-Thuy; Zhao, Shaohua; Ball, Takiyah; Haro, Jovita; Pecic, Gary; Joyce, Kevin; Fedorka-Cray, Paula J.; Whichard, Jean M.; McDermott, Patrick F.

2010-01-01

180

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.  

PubMed Central

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions. PMID:2088195

Boeckh, M; Lode, H; Deppermann, K M; Grineisen, S; Shokry, F; Held, R; Wernicke, K; Koeppe, P; Wagner, J; Krasemann, C

1990-01-01

181

Quinolone-resistant mutations of the gyrA gene of Escherichia coli  

Microsoft Academic Search

DNA fragments of 8.5 kb containing the gyrA gene were cloned from Escherichia coli KL-16 and from four spontaneous gyrA mutants which showed various levels of resistance to quinolones. The gyrA gene was situated at about 4 kb in front of the nrdA gene and transcribed counterclockwise on the E. coli chromosome. It encoded a polypeptide of 875 amino acids

Hiroaki Yoshida; Tsuyoshi Kojima; Jun-ichi Yamagishi; Shinichi Nakamura

1988-01-01

182

The qualitative and quantitative determination of quinolones of first and second generation by capillary electrophoresis  

Microsoft Academic Search

Capillary electrophoresis (CE) was applied to the study of 10 quinolones of first and second generation — nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, fleroxacin, and flumequine. Separation was performed on a fused silica capillary (75 ?m–60 cm) using a phosphate buffer (pH 7.0, 125 mM). Detection was at 214 nm. Only norfloxacin and ciprofloxacin cannot

C Fierens; S Hillaert; W Van den Bossche

2000-01-01

183

In Vitro Release of New Quinolones from Biodegradable Systems: A Comparative Study  

Microsoft Academic Search

A new biodegradable delivery system based on low molecular weight poly(lactic acid) has been formualted, with potential application in the sustained antibiotic release against bone infection. The in vitro release of two new quinolones (ofloxacin and ciprofloxacin) from the biodegradable matrix showed that the delivery of ofloxacin from the matrix lasted fifty-six days, whereas that of ciprofloxacin lasted fifty-one days.

A. G. Andreopoulos; T. Korakis; E. Dounis; A. Anastasiadis; P. Tzivelekis; K. Kanellakopoulou

1996-01-01

184

Liquid chromatographic determination of quinolones in water and human urine samples after microextraction by packed sorbent.  

PubMed

A method for the simultaneous determination of quinolones in water and urine samples by microextraction in a sorbent-packed syringe (MEPS) with LC is described. MEPS is a new miniaturized SPE technique that can be used with chromatographic instruments without any modifications. In MEPS, approximately 1 mg of the solid packing material is inserted into a syringe (100-250 microL) as a plug. Sample preparation takes place on the packed bed. The new method is promising, easy to use, economical, and rapid. The determination of quinolones in groundwater and urine was performed using MEPS as a sample preparation method with LC-UV determination. Four quinolone antibiotics--enrofloxacin, enoxacin, danofloxacin, and nalidixic acid--in groundwater and urine samples were used as analytes. The extraction recovery was found to be between 64.9 and 98.9%. The results showed high correlation coefficients (R2 > 0.992) for all of the analytes within the calibration range. The LOQ was between 0.091 and 0.315 ng/mL. PMID:22468369

Rani, Susheela; Kumar, Ashwini; Malik, Ashok Kumar; Singh, Baldev

2012-01-01

185

Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones.  

PubMed

Abstract Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin). PMID:25058176

Van Bambeke, Françoise

2014-11-01

186

In Vitro Activities of Cephalosporins and Quinolones against Escherichia coli Strains Isolated from Diarrheic Dairy Calves  

PubMed Central

The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from dairy calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these factors. From 11 to 18% of the E. coli strains were resistant to cephalothin, nalidixic acid, enoxacin, and enrofloxacin. However, cefuroxime, cefotaxime, and cefquinome were highly effective against the E. coli isolates tested. Some significant differences (P < 0.05) in resistance to quinolones between the strains producing potential virulence factors and nonfimbriated, nontoxigenic, eae-negative strains were found. Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains. Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains. Thus, the results of this study suggest that the bovine E. coli strains that produce some potential virulence factors are more sensitive to quinolones than those that do not express these factors. PMID:10049259

Orden, José Antonio; Ruiz-Santa-Quiteria, José Antonio; García, Silvia; Cid, Dolores; de la Fuente, Ricardo

1999-01-01

187

Protein Interactions in Genome Maintenance as Novel Antibacterial Targets  

PubMed Central

Antibacterial compounds typically act by directly inhibiting essential bacterial enzyme activities. Although this general mechanism of action has fueled traditional antibiotic discovery efforts for decades, new antibiotic development has not kept pace with the emergence of drug resistant bacterial strains. These limitations have severely restricted the therapeutic tools available for treating bacterial infections. Here we test an alternative antibacterial lead-compound identification strategy in which essential protein-protein interactions are targeted rather than enzymatic activities. Bacterial single-stranded DNA-binding proteins (SSBs) form conserved protein interaction “hubs” that are essential for recruiting many DNA replication, recombination, and repair proteins to SSB/DNA nucleoprotein substrates. Three small molecules that block SSB/protein interactions are shown to have antibacterial activity against diverse bacterial species. Consistent with a model in which the compounds target multiple SSB/protein interactions, treatment of Bacillus subtilis cultures with the compounds leads to rapid inhibition of DNA replication and recombination, and ultimately to cell death. The compounds also have unanticipated effects on protein synthesis that could be due to a previously unknown role for SSB/protein interactions in translation or to off-target effects. Our results highlight the potential of targeting protein-protein interactions, particularly those that mediate genome maintenance, as a powerful approach for identifying new antibacterial compounds. PMID:23536821

Walsh, Brian W.; Shapiro, Walker; Simmons, Lyle A.; Keck, James L.

2013-01-01

188

Evaluation of the Antibacterial Activity of Patchouli Oil  

PubMed Central

In the present study, the antimicrobial tests of patchouli oil were studied by using molecular docking technology and antimicrobial test in vitro. Five biological macromolecule enzymes, required by the bacteria in the process of biosynthesis were selected as target molecules. Five antibiotics benzylpenicillin, sulfadiazine, trimethoprim, rifampicin and ciprofloxacin, which are generally acknowledged as antibacterial drugs, were selected as reference compounds. The 3 three-dimensional (3D) structures of the 5 reference compounds and 26 compounds from patchouli oil were established by using surflex-dock software (8.1). And the 3D structures of five biological macromolecule enzymes derived from Protein Data Bank (PDB). Molecular docking was carried out between the 31 chemical compounds (ligands) and the 5 enzymes (receptors) by using surflex-dock function. Furthermore, the antibacterial effects of 31 chemical compounds were investigated by the scoring function after molecular docking was completed. By comparing the scoring result of 26 compounds in patchouli oil with 5 compared components, we inferred antibacterial activity in about 26 compounds in patchouli oil. On the other hand, six frequently-used pathogenic bacteria were selected for antimicrobial test in vitro, patchouli oil and its two major compounds: (-)-patchouli alcohol and pogostone, which their contents exceeded 60% in patchouli oil samples, were selected antibacterial agents. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were also determined. Molecular docking technology and antimicrobial test in vitro proved that patchouli oil had strong antimicrobial effects. Particularly, pogostone and (-)-patchouli alcohol have potent antimicrobial activity. PMID:24250637

Yang, Xian; Zhang, Xue; Yang, Shui-Ping; Liu, Wei-Qi

2013-01-01

189

Characterization of ESBLs and associated quinolone resistance in Escherichia coli and Klebsiella pneumoniae isolates from an urban wastewater treatment plant in Algeria.  

PubMed

The aim of the study was the characterization of extended spectrum beta-lactamases (ESBLs) and quinolone resistance in cefotaxime-resistant coliform isolates from a wastewater treatment plant (WWTP). ESBLs were detected in 19 out of 24 isolates (79%) from raw water and in 21 out of 24 isolates (87.5%) from treated water, identified as Klebsiella pneumoniae and Escherichia coli. Molecular characterization of ESBLs and quinolone resistance showed allele profiles CTX-M-15 (3), CTX-M-3 (5), CTX-M-15+qnrB1 (1), CTX-M-3+qnrB1 (1), CTX-M-15+aac-(6')-Ib-cr (4), and CTX-M-15+qnrB1+aac-(6')-Ib-cr (7). A double mutation S83L and D87N (GyrA) and a single mutation S80I (ParC) were detected in ciprofloxacin-resistant E. coli isolates. In K. pneumoniae, mutations S83I (GyrA)+S80I (ParC) or single S80I mutation were detected in ciprofloxacin-resistant isolates, and no mutation was observed in ciprofloxacin-susceptible isolates. bla(CTX-M), qnrB1, and aac-(6')-Ib-cr were found, respectively, in these genetic environments: ISEcp1-bla(CTX-M)-orf477, orf1005-orf1-qnrB1, and Tn1721-IS26-aac-(6')-Ib-cr-bla(OXA-1)-catB4. bla(CTX-M-15) was located on IncF plasmid in E. coli and bla(CTX-M-3) on IncL/M plasmid in both species (E. coli and K. pneumoniae). E. coli isolates were affiliated to the phylogroups/MLST: D/ST405 (CC405), A/ST10 (CC10), A/ST617 (CC10), and B1/ST1431. K. pneumoniae isolates belonged to phylogroup KpI and to sequence types ST15, ST17, ST36, ST48, ST54, and ST147. The study showed a multi-drug resistance at the inflow and outflow of the WWTP, with ESBL production, plasmid-mediated quinolones resistance, and mutations in topoisomerases. The findings highlight the similarity of antibiotic resistance mechanisms in the clinical setting and the environment, and the role of the latter as a source of dissemination of resistance genes. PMID:23952363

Alouache, Souhila; Estepa, Vanesa; Messai, Yamina; Ruiz, Elena; Torres, Carmen; Bakour, Rabah

2014-02-01

190

Quinolone compounds enhance delta-aminolevulinic acid-induced accumulation of protoporphyrin IX and photosensitivity of tumour cells.  

PubMed

Exogenous ?-aminolevulinic acid (ALA)-induced photodynamic therapy (PDT) has been used in the treatment of cancer. To obtain a high efficacy of ALA-PDT, we have screened various chemicals affecting ALA-induced accumulation of protoporphyrin in cancerous cells. When HeLa cells were treated with quinolone chemicals including enoxacin, ciprofloxacin or norfloxacin, the ALA-induced photodamage accompanied by the accumulation of protoporphyrin was stronger than that with ALA alone. Thus, quinolone compounds such as enoxacin, ciprofloxacin and norfloxacin enhanced ALA-induced photodamage. The increased ALA-induced photodamage in enoxacin-treated HeLa cells was decreased by haemin or ferric-nitrilotriacetate (Fe-NTA), suggesting that an increase in iron supply cancels the accumulation of protoporphyrin. On the other hand, the treatment of the cells with ALA plus an inhibitor of haem oxygenase, Sn-protoporphyrin, led to an increase in the photodamage and the accumulation of protoporphyrin compared with those upon treatment with ALA alone, indicating that the cessation of recycling of iron from haem augments the accumulation. The use of quinolones plus Sn-protoporphyrin strongly enhances ALA-induced photodamage. To examine the mechanisms involved in the increased accumulation of protoporphyrin, we incubated ferric chloride with an equivalent amount of quinolones. Iron-quinolone complexes with visible colours with a maximum at 450 nm were formed. The levels of iron-metabolizing proteins in enoxacin- or ciprofloxacin-treated cells changed, indicating that quinolones decrease iron utilization for haem biosynthesis. Hence, we now propose that the use of quinolones in combination with ALA may be an extremely effective approach for the treatment modalities for PDT of various tumour tissues in clinical practice. PMID:20961864

Ohgari, Yoshiko; Miyata, Yoshinobu; Chau, Tuan Thanh; Kitajima, Sakihito; Adachi, Yasushi; Taketani, Shigeru

2011-02-01

191

Measuring the comparative efficacy of antibacterial agents for acute otitis media: the "Pollyanna phenomenon".  

PubMed

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media. PMID:1731027

Marchant, C D; Carlin, S A; Johnson, C E; Shurin, P A

1992-01-01

192

Antibacterial Biomimetic Hybrid Films  

PubMed Central

In this work, we present a novel method to prepare a hybrid coating based on dextran grafted to a substrate and embedded with silver nanoparticles (Ag NPs). First, the Ag NPs are synthesized in situ in the presence of oxidized dextran in solution. Second, the oxidized dextran is exposed to an amine functionalized surface resulting in the simultaneous grafting of dextran and the trapping of Ag NPs within the layer. The NP loading is controlled by the concentration of silver nitrate, which is 2 mM (DEX-Ag2) and 5 mM (DEX-Ag5). The dried film thickness increases with silver nitrate concentration from 2 nm for dextran to 7 nm and 12 nm for DEX-Ag2 and DEX-Ag5, respectively. The grafted dextran film displays features with a diameter and height of ~ 50 nm and 2 nm, respectively. For the DEX-Ag2 and DEX-Ag5, the dextran features as well as individual Ag NPs (~ 5 nm) and aggregates of Ag NPs are observed. Larger and more irregular aggregates are observed for DEX-Ag5. Overall, the Ag NPs are embedded in the dextran film as suggested by AFM and UVO studies. In terms of its antimicrobial activity, DEX-Ag2 resists bacterial adhesion to a greater extent than DEX-Ag5, which in turn is better than dextran and silicon. Because these antibacterial hybrid coatings can be grafted to a variety of surfaces, many biomedical applications can be envisioned, ranging from coating implants to catheters. PMID:23807896

Ferrer, M. Carme Coll; Hickok, Noreen J.; Eckmann, David M.; Composto, Russell J.

2012-01-01

193

Antimycobacterial and Antibacterial Activity of Allium sativum Bulbs.  

PubMed

Tuberculosis is one of the major public health problems faced globally. Resistance of Mycobacterium tuberculosis to antitubercular agents has called for an urgent need to investigate newer drugs to combat tuberculosis. Garlic (Allium sativum) is an edible plant which has generated a lot of curiosity throughout human history as a medicinal plant. Garlic contains sulfur compounds like allicin, ajoene, allylmethyltrisulfide, diallyltrisulfide, diallyldisulphide and others which exhibit various biological properties like antimicrobial, anticancer, antioxidant, immunomodulatory, antiinflammatory, hypoglycemic, and cardiovascular effects. According to various traditional systems of medicine, garlic is one of the established remedies for tuberculosis. The objective of the current study was to investigate in vitro antimycobacterial activity as well as anti-bacterial activity of various extracts rich in specific phytoconstituents from garlic. Preparation of garlic extracts was done based on the chemistry of the constituents and their stability. The estimation of in vitro antimycobacterial activity of different garlic extracts was done using Resazurin microtire plate assay technique whereas activity of garlic oil was evaluated by colony count method. The antibacterial activity of extracts and oil was estimated by zone of inhibition method. Extracts of garlic rich in allicin and ajoene showed appreciable antimycobacterial activity as compared to standard drugs. Garlic oil demonstrated significant antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus. PMID:25035540

Viswanathan, V; Phadatare, A G; Mukne, Alka

2014-05-01

194

Antimycobacterial and Antibacterial Activity of Allium sativum Bulbs  

PubMed Central

Tuberculosis is one of the major public health problems faced globally. Resistance of Mycobacterium tuberculosis to antitubercular agents has called for an urgent need to investigate newer drugs to combat tuberculosis. Garlic (Allium sativum) is an edible plant which has generated a lot of curiosity throughout human history as a medicinal plant. Garlic contains sulfur compounds like allicin, ajoene, allylmethyltrisulfide, diallyltrisulfide, diallyldisulphide and others which exhibit various biological properties like antimicrobial, anticancer, antioxidant, immunomodulatory, antiinflammatory, hypoglycemic, and cardiovascular effects. According to various traditional systems of medicine, garlic is one of the established remedies for tuberculosis. The objective of the current study was to investigate in vitro antimycobacterial activity as well as anti-bacterial activity of various extracts rich in specific phytoconstituents from garlic. Preparation of garlic extracts was done based on the chemistry of the constituents and their stability. The estimation of in vitro antimycobacterial activity of different garlic extracts was done using Resazurin microtire plate assay technique whereas activity of garlic oil was evaluated by colony count method. The antibacterial activity of extracts and oil was estimated by zone of inhibition method. Extracts of garlic rich in allicin and ajoene showed appreciable antimycobacterial activity as compared to standard drugs. Garlic oil demonstrated significant antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus. PMID:25035540

Viswanathan, V.; Phadatare, A. G.; Mukne, Alka

2014-01-01

195

Synthesis and antibacterial activity of nitroaryl thiadiazole-gatifloxacin hybrids.  

PubMed

A number of gatifloxacin analogues containing a nitroaryl-1,3,4-thiadiazole moiety attached to the piperazine ring at C-7 position were prepared and evaluated as antibacterial agents against a panel of gram-positive and gram-negative bacteria. Among synthesized compounds, nitrofuran analog 6a exhibited more potent inhibitory activity against gram-positive bacteria including Staphylococcus epidermidis (MIC=0.0078 microg/mL), Bacillus subtilis (MIC=0.0039 microg/mL), Enterococcus faecalis (MIC=0.125 microg/mL) and Micrococcus luteus (MIC=0.125 microg/mL), with respect to other synthesized compounds and reference drug gatifloxacin. The target compounds were also assessed for their cytotoxic activity against normal mouse fibroblast (NIH/3T3) cells using MTT assay. The results indicated that these compounds exhibit antibacterial activity at non-cytotoxic concentrations. PMID:18950903

Jazayeri, Seyyedehsamira; Moshafi, Mohammad Hassan; Firoozpour, Loghman; Emami, Saeed; Rajabalian, Saeed; Haddad, Mitra; Pahlavanzadeh, Farahnaz; Esnaashari, Manzarbanoo; Shafiee, Abbas; Foroumadi, Alireza

2009-03-01

196

ANTIBACTERIAL SCREENING OF CITRULLUS COLOCYNTHIS  

Microsoft Academic Search

Crude ethanolic extracts of fruits, leaves, stems and roots of Citrulus colocynthis Schrad were examined for their antibacterial potentialities against Gram positive and Gram negative bacilli. Ethanolic extracts of fruits, leaves, stems and roots were found to be active against Gram positive bacilli, viz., Bacilus pumilus and Staphylococcus aureus, while fruit and root extracts in double strength gave positive results

USMAN MEMON; ABDUL HAKEEM BROHI; SYED WASEEMUDDIN AHMED; IQBAL AZHAR; HUSAN BANO

197

In Vitro and In Vivo Antibacterial Activities of DC-159a, a New Fluoroquinolone?  

PubMed Central

DC-159a is a new 8-methoxy fluoroquinolone that possesses a broad spectrum of antibacterial activity, with extended activity against gram-positive pathogens, especially streptococci and staphylococci from patients with community-acquired infections. DC-159a showed activity against Streptococcus spp. (MIC90, 0.12 ?g/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 ?g/ml. The MIC90s of DC-159a against Staphylococcus spp. were 0.5 ?g/ml or less. Against quinolone- and methicillin-resistant Staphylococcus aureus strains, however, the MIC90 of DC-159a was 8 ?g/ml. DC-159a was the most active against Enterococcus spp. (MIC90, 4 to 8 ?g/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC90s of DC-159a against Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae were 0.015, 0.06, and 0.25 ?g/ml, respectively. The activity of DC-159a against Mycoplasma pneumoniae was eightfold more potent than that of levofloxacin. The MICs of DC-159a against Chlamydophila pneumoniae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC90s of DC-159a against Peptostreptococcus spp., Clostridium difficile, and Bacteroides fragilis were 0.5, 4, and 2 ?g/ml, respectively; and among the quinolones tested it showed the highest level of activity against anaerobic organisms. DC-159a demonstrated rapid bactericidal activity against quinolone-resistant Streptococcus pneumoniae strains both in vitro and in vivo. In vitro, DC-159a showed faster killing than moxifloxacin and garenoxacin. The bactericidal activity of DC-159a in a murine muscle infection model was revealed to be superior to that of moxifloxacin. These activities carried over to the in vivo efficacy in the murine pneumonia model, in which treatment with DC-159a led to bactericidal activity superior to those of the other agents tested. PMID:17938194

Hoshino, Kazuki; Inoue, Kazue; Murakami, Yoichi; Kurosaka, Yuichi; Namba, Kenji; Kashimoto, Yoshinori; Uoyama, Saori; Okumura, Ryo; Higuchi, Saito; Otani, Tsuyoshi

2008-01-01

198

In Vitro and In Vivo Antibacterial Activities of DK-507k, a Novel Fluoroquinolone  

PubMed Central

The antibacterial activities of DK-507k, a novel quinolone, were compared with those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as sitafloxacin and was as active as or up to eightfold more active than gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae, methicillin-susceptible and methicillin-resistant Staphylococcus aureus, and coagulase-negative staphylococci. DK-507k was as active as or 4-fold more active than garenoxacin and 2- to 16-fold more active than gatifloxacin and moxifloxacin against ciprofloxacin-resistant strains of S. pneumoniae, including clinical isolates and in vitro-selected mutants with known mutations. DK-507k inhibited all ciprofloxacin-resistant strains of S. pneumoniae at 1 ?g/ml. A time-kill assay with S. pneumoniae showed that DK-507k was more bactericidal than gatifloxacin and moxifloxacin. The activities of DK-507k against most members of the family Enterobacteriaceae were comparable to those of ciprofloxacin and equal to or up to 32-fold higher than those of gatifloxacin, levofloxacin, moxifloxacin, and garenoxacin. DK-507k was fourfold less active than sitafloxacin and ciprofloxacin against Pseudomonas aeruginosa, while it was two to four times more potent than levofloxacin, gatifloxacin, moxifloxacin, and garenoxacin against P. aeruginosa. In vivo, intravenous treatment with DK-507k was more effective than that with gatifloxacin and moxifloxacin against systemic infections caused by S. aureus, S. pneumoniae, and P. aeruginosa in mice. In a mouse model of pneumonia due to penicillin-resistant S. pneumoniae, DK-507k administered subcutaneously showed dose-dependent efficacy and eliminated the bacteria from the lungs, whereas gatifloxacin and moxifloxacin had no significant efficacy. Oral treatment with DK-507k was slightly more effective than that with ciprofloxacin in a rat model of foreign body-associated urinary tract infection caused by a P. aeruginosa isolate for which the MIC of DK-507k was fourfold higher than that of ciprofloxacin. Oral administration of DK-507k to rats achieved higher peak concentrations in serum and higher concentrations in cumulative urine than those achieved with ciprofloxacin. These data indicate the potential advantages of DK-507k over other quinolones for the treatment of a wide range of community-acquired infections. PMID:14638477

Otani, Tsuyoshi; Tanaka, Mayumi; Ito, Emi; Kurosaka, Yuichi; Murakami, Yoichi; Onodera, Kiyomi; Akasaka, Takaaki; Sato, Kenichi

2003-01-01

199

Chemical composition and antibacterial activities of Illicium verum against antibiotic-resistant pathogens.  

PubMed

In recent years, human pathogenic microorganisms have developed multiple drug resistance and caused serious nosocomial infections. In this study, we identified four new antimicrobial compounds from the Chinese herbal medicine Illicium verum and assessed their antibacterial efficacies. The supercritical CO? and ethanol extracts of Illicium verum showed substantial antibacterial activity against 67 clinical drug-resistant isolates, including 27 Acinetobacter baumannii, 20 Pseudomonas aeruginosa, and 20 methicillin-resistant Staphylococcus aureus. The diethyl ether (EE) fraction obtained from partition extraction and supercritical CO? extracts revealed an antibacterial activity with a minimum inhibitory concentration value of 0.15-0.70?mg/mL and 0.11?mg/mL, respectively. The EE fraction of I. verum showed synergetic effects with some commercial antibiotics. The antimicrobial mechanism was investigated with killing curves and scanning electron microscopy observation. The chemical components of the extracts were analyzed by spectrophotometry; (E)-anethole, anisyl acetone, anisyl alcohol, and anisyl aldehyde exhibited antibacterial activity against different clinical isolates. These extracts from I. verum can be further developed into antibiotic medicines due to their proven antibacterial activity. PMID:20828316

Yang, Jyh-Ferng; Yang, Cheng-Hong; Chang, Hsueh-Wei; Yang, Cheng-San; Wang, Shao-Ming; Hsieh, Ming-Che; Chuang, Li-Yeh

2010-10-01

200

Antibacterial resistant bacteria in surficial sediments near salmon net-cage farms in Puget Sound, Washington  

Microsoft Academic Search

Antibacterials are used in medicated fish feed at fish farms located in Puget Sound, Washington. These compounds include oxytetracycline (OTC), amoxycillin, and Romet® 30 (a drug composed of sulfadimethioxine and ormetoprim). In this study we collected surficial sediment samples at three different commercial salmon net-cage farms during the summer and early fall of 1992. The three different farms varied in

Russell P Herwig; James P Gray; Donald P Weston

1997-01-01

201

Antibacterial activity of traditional medicinal plants used by Haudenosaunee peoples of New York State  

Microsoft Academic Search

BACKGROUND: The evolution and spread of antibiotic resistance, as well as the evolution of new strains of disease causing agents, is of great concern to the global health community. Our ability to effectively treat disease is dependent on the development of new pharmaceuticals, and one potential source of novel drugs is traditional medicine. This study explores the antibacterial properties of

Frank M Frey; Ryan Meyers

2010-01-01

202

Graphene oxide-based antibacterial cotton fabrics.  

PubMed

Graphene oxide (GO) is an excellent bacteria-killing nanomaterial. In this work, macroscopic applications of this promising nanomaterial by fixing GO sheets onto cotton fabrics, which possess strong antibacterial property and great laundering durability, are reported. The GO-based antibacterial cotton fabrics are prepared in three ways: direct adsorption, radiation-induced crosslinking, and chemical crosslinking. Antibacterial tests show that all these GO-containing fabrics possess strong antibacterial property and could inactivate 98% of bacteria. Most significantly, these fabrics can still kill >90% bacteria even after being washed for 100 times. Also importantly, animal tests show that GO-modified cotton fabrics cause no irritation to rabbit skin. Hence, it is believed that these flexible, foldable, and re-usable GO-based antibacterial cotton fabrics have high promise as a type of new nano-engineered antibacterial materials for a wide range of applications. PMID:23483725

Zhao, Jinming; Deng, Bo; Lv, Min; Li, Jingye; Zhang, Yujie; Jiang, Haiqing; Peng, Cheng; Li, Jiang; Shi, Jiye; Huang, Qing; Fan, Chunhai

2013-09-01

203

Antibacterial activity on Citrullus colocynthis Leaf extract.  

PubMed

Studies on the antibacterial activities of the leaf extract of Citrullus colocynthis (Cucurbitaceae), a medicinal plant used for the treatment of various ailments was carried out using agar disc diffusion technique. The results revealed that the crude acetone extract exhibited antibacterial activities against Pseudomonas aeruginosa with zones of inhibition measuring 14.0mm. The chloroform leaf extract exhibited no antibacterial activity against Staphylococcus aureus. The minimum inhibitory concentration for the chloroform extract was 4.0mm for Escherichia coli. PMID:22557336

Gowri, S Shyamala; Priyavardhini, S; Vasantha, K; Umadevi, M

2009-07-01

204

Antibiotics Threaten Wildlife: Circulating Quinolone Residues and Disease in Avian Scavengers  

PubMed Central

Antibiotic residues that may be present in carcasses of medicated livestock could pass to and greatly reduce scavenger wildlife populations. We surveyed residues of the quinolones enrofloxacin and its metabolite ciprofloxacin and other antibiotics (amoxicillin and oxytetracycline) in nestling griffon Gyps fulvus, cinereous Aegypius monachus and Egyptian Neophron percnopterus vultures in central Spain. We found high concentrations of antibiotics in the plasma of many nestling cinereous (57%) and Egyptian (40%) vultures. Enrofloxacin and ciprofloxacin were also found in liver samples of all dead cinereous vultures. This is the first report of antibiotic residues in wildlife. We also provide evidence of a direct association between antibiotic residues, primarily quinolones, and severe disease due to bacterial and fungal pathogens. Our results indicate that, by damaging the liver and kidney and through the acquisition and proliferation of pathogens associated with the depletion of lymphoid organs, continuous exposure to antibiotics could increase mortality rates, at least in cinereous vultures. If antibiotics ingested with livestock carrion are clearly implicated in the decline of the vultures in central Spain then it should be considered a primary concern for conservation of their populations. PMID:18197254

Lemus, Jesus A.; Blanco, Guillermo; Grande, Javier; Arroyo, Bernardo; Garcia-Montijano, Marino; Martinez, Felix

2008-01-01

205

Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A  

PubMed Central

Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e., in gyrA, gyrB, or parC) correlating with the resistance levels observed. Active efflux, through upregulation of multipartite efflux systems, has also been previously reported as contributing mechanism for other serovars. Therefore, we investigated also the occurrence of non-target gene mutations in regulatory regions affecting efflux pump expression. However, no mutation was detected in these regions in both Typhi and Paratyphi isolates of this study. Besides, no overexpression of the major efflux systems was observed for these isolates. Nevertheless, a large deletion of 2334 bp was identified in the acrS-acrE region of all S. Typhi strains but which did not affect the resistance phenotype. As being specific to S. Typhi, this deletion could be used for specific molecular detection purposes. In conclusion, the different levels of quinolone or FQ resistance in both S. Typhi and S. Paratyphi A seem to rely only on target modifications. PMID:24478769

Baucheron, Sylvie; Monchaux, Isabelle; Le Hello, Simon; Weill, Francois-Xavier; Cloeckaert, Axel

2014-01-01

206

Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa  

PubMed Central

Pseudomonas aeruginosa is an opportunistic pathogen that controls numerous virulence factors through intercellular signals. This bacterium has two quorum-sensing systems (las and rhl), which act through the intercellular signals N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and N-butyryl-l-homoserine lactone (C4-HSL), respectively. P. aeruginosa also produces a third intercellular signal that is involved in virulence factor regulation. This signal, 2-heptyl-3-hydroxy-4-quinolone [referred to as the Pseudomonas quinolone signal (PQS)], is a secondary metabolite that is part of the P. aeruginosa quorum-sensing hierarchy. PQS can induce both lasB (encodes LasB elastase) and rhlI (encodes the C4-HSL synthase) in P. aeruginosa and is produced maximally during the late stationary phase of growth. Because PQS is an intercellular signal that is part of the quorum-sensing hierarchy and controls multiple virulence factors, we began basic studies designed to elucidate its biosynthetic pathway. First, we present data that strongly suggest that anthranilate is a precursor for PQS. P. aeruginosa converted radiolabeled anthranilate into radioactive PQS, which was bioactive. We also found that an anthranilate analog (methyl anthranilate) would inhibit the production of PQS. This analog was then shown to have a major negative effect on elastase production by P. aeruginosa. These data provide evidence that precursors of intercellular signals may provide viable targets for the development of therapeutic treatments that will reduce P. aeruginosa virulence. PMID:11573001

Calfee, M. Worth; Coleman, James P.; Pesci, Everett C.

2001-01-01

207

Antibacterial screening of Citrullus colocynthis.  

PubMed

Crude ethanolic extracts of fruits, leaves, stems and roots of Citrullus colocynthis Schrad were examined for their antibacterial potentialities against Gram positive and Gram negative bacilli. Ethanolic extracts of fruits, leaves, stems and roots were found to be active against Gram positive bacilli, viz., Bacillus pumilus and Staphylococcus aureus, while fruit and root extracts in double strength gave positive results against Gram positive bacillus (Bacillus subtilis). The Gram negative bacilli viz., Escherichia coli and Pseudomonas aeruginosa showed no response. PMID:16414561

Memon, Usman; Brohi, Abdul Hakeem; Ahmed, Syed Waseemuddin; Azhar, Iqbal; Bano, Husan

2003-01-01

208

The Antibacterial Activity of Haematin  

Microsoft Academic Search

SUMMARY: Haematin in concentrations of 1 \\/l,OOO,OOO-1\\/2,000,000 inhibited the growth of a number of bacteria most of which were aerobic sporing bacilli. Deutero- haematin and mesohaematin were also inhibitory, but not haematohaematin, urohaematin and a number of iron-free porphyrin derivatives. In a few cases whole blood was inhibitory, but generally only trypsin-digested laked red cells. The mechanism of the antibacterial

W. E. VAN HEYNINGEN

1951-01-01

209

Synthesis of novel bisindolylmethane Schiff bases and their antibacterial activity.  

PubMed

In an effort to develop new antibacterial drugs, some novel bisindolylmethane derivatives containing Schiff base moieties were prepared and screened for their antibacterial activity. The synthesis of the bisindolylmethane Schiff base derivatives 3-26 was carried out in three steps. First, the nitro group of 3,3'-((4-nitrophenyl)-methylene)bis(1H-indole) (1) was reduced to give the amino substituted bisindolylmethane 2 without affecting the unsaturation of the bisindolylmethane moiety using nickel boride in situ generated. Reduction of compound 1 using various catalysts showed that combination of sodium borohydride and nickel acetate provides the highest yield for compound 2. Bisindolylmethane Schiff base derivatives were synthesized by coupling various benzaldehydes with amino substituted bisindolylmethane 2. All synthesized compounds were characterized by various spectroscopic methods. The bisindolylmethane Schiff base derivatives were evaluated against selected Gram-positive and Gram-negative bacterial strains. Derivatives having halogen and nitro substituent display weak to moderate antibacterial activity against Salmonella typhi, S. paratyphi A and S. paratyphi B. PMID:25102118

Imran, Syahrul; Taha, Muhammad; Ismail, Nor Hadiani; Khan, Khalid Mohammed; Naz, Farzana; Hussain, Memona; Tauseef, Saima

2014-01-01

210

An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae  

PubMed Central

Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea. PMID:22089602

Patel, Achchhe Lal; Chaudhry, Uma; Sachdev, Divya; Sachdeva, Poonam Nagpal; Bala, Manju; Saluja, Daman

2011-01-01

211

Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II: broad-spectrum antibacterial agents with reduced hERG activity.  

PubMed

Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. Aminopiperidines that have a bicyclic aromatic moiety linked through a carbon to an ethyl bridge, such as 1, generally show potent broad-spectrum antibacterial activity, including quinolone-resistant isolates, but suffer from potent hERG inhibition (IC(50)= 3 ?M for 1). We now disclose the finding that new analogues of 1 with an N-linked cyclic amide moiety attached to the ethyl bridge, such as 24m, retain the broad-spectrum antibacterial activity of 1 but show significantly less hERG inhibition (IC(50)= 31 ?M for 24m) and higher free fraction than 1. One optimized analogue, compound 24l, showed moderate clearance in the dog and promising efficacy against Staphylococcus aureus in a mouse thigh infection model. PMID:21999508

Reck, Folkert; Alm, Richard; Brassil, Patrick; Newman, Joseph; Dejonge, Boudewijn; Eyermann, Charles J; Breault, Gloria; Breen, John; Comita-Prevoir, Janelle; Cronin, Mark; Davis, Hajnalka; Ehmann, David; Galullo, Vincent; Geng, Bolin; Grebe, Tyler; Morningstar, Marshall; Walker, Phil; Hayter, Barry; Fisher, Stewart

2011-11-24

212

Quinolone-Resistant Uropathogenic Escherichia coli Strains from Phylogenetic Group B2 Have Fewer Virulence Factors than Their Susceptible Counterparts  

PubMed Central

The prevalence of 31 virulence factors was analyzed among nalidixic acid-susceptible and -resistant Escherichia coli strains from phylogenetic group B2. Hemolysin, cytotoxic necrotizing factor 1, and S and F1C fimbriae genes were less prevalent among nalidixic acid-resistant E. coli strains. Quinolone resistance may be associated with a decrease in the presence of some virulence factors. PMID:15956432

Horcajada, Juan P.; Soto, Sara; Gajewski, Abby; Smithson, Alex; Jimenez de Anta, M. Teresa; Mensa, Josep; Vila, Jordi; Johnson, James R.

2005-01-01

213

Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3?.  

PubMed

The synthesis, GSK-3? inhibitory activity, and anti-microbial activity of bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3-carboxylic acid scaffold were studied. Kinase selectivity profiling indicated that members of this class were potent and highly selective GSK-3 inhibitors. PMID:21873061

Cociorva, Oana M; Li, Bei; Nomanbhoy, Tyzoon; Li, Qiang; Nakamura, Ayako; Nakamura, Kai; Nomura, Masahiro; Okada, Kyoko; Seto, Shigeki; Yumoto, Kazuhiro; Liyanage, Marek; Zhang, Melissa C; Aban, Arwin; Leen, Brandon; Szardenings, Anna Katrin; Rosenblum, Jonathan S; Kozarich, John W; Kohno, Yasushi; Shreder, Kevin R

2011-10-01

214

Characterization of Mutations in DNA Gyrase and Topoisomerase IV Involved in Quinolone Resistance of Mycoplasma gallisepticum Mutants Obtained In Vitro  

Microsoft Academic Search

Mycoplasma gallisepticum is responsible for chronic respira- tory diseases of chickens and sinusitis of turkeys (17). Control by antimicrobials is sometimes necessary to minimize its trans- mission in case of an outbreak. M. gallisepticum is known to be susceptible to several antimicrobials (10, 17) but can develop resistance against some of the quinolones used in veterinary medicine (14). Unlike human

A. K. Reinhardt; C. M. Bebear; M. Kobisch; I. Kempf; A. V. Gautier-Bouchardon

2002-01-01

215

Marine algae: screening for a potent antibacterial agent.  

PubMed

This study was done to investigate the antimicrobial potentiality of the marine algae collected from different coastal regions of Gujarat and screened for the same. Twenty-six marine algae belonging to Rhodophyceae, Chlorophyceae and Phaeophyceae were screened for their potential antibacterial activity against five clinically important bacterial strains, namely Bacillus cereus, Micrococcus flavus, Citrobacter freundii, Klebsiella pneumoniae and Pseudomonas testosterone. Acetone and methanol were used for extraction; and the extracted yield was more when the solvent used was methanol. The antibacterial activity was done by both Agar disc diffusion method and Agar ditch method. The five bacterial strains showed varied response towards marine algal extracts. The most susceptible bacteria was B. cereus followed by K. pneumoniae and C. freundii while the most resistant bacteria were M. flavus and P. testosteroni. Among the 26 algae screened, E. intestinalis was the most potent alga and thus, this alga was selected for further studies. E. intestinalis was extracted in petroleum ether, 1,4-dioxan, acetone, methanol and DMF, and their antibacterial activity was studied against the above-stated five bacterial strains using agar disc method. Maximum extractive value of E. intestinalis was in methanol (2.05%) and minimum was in acetone (0.38%). The most susceptible bacteria was K. pneumoniae and maximum antibacterial activity was shown by petroleum ether extract and minimum was shown by 1,4-dioxan extract. The most resistant bacteria were M. flavus and C. freundii. The MIC values of E. intestinalis extracts ranged from 2500-9.765 microg/0.5 ml against B. cereus and K. pneumoniae. From these results it is concluded that the acetone extract of E. intestinalis is the most potent extract and can be used as a lead molecule in drug discovery in inhibiting some of the bacterial strains. E. intestinalis can be used as a promising novel marine antimicrobial agent in the coming years. PMID:17594989

Nair, Ratish; Chabhadiya, Rajesh; Chanda, Sumitra

2007-01-01

216

Characterization of Ribosomal Binding and Antibacterial Activities Using Two Orthogonal High-Throughput Screens  

PubMed Central

We report here the affinity and antibacterial activity of a structurally similar class of neomycin dimers. The affinity of the dimer library for rRNA was established by using a screen that measures the displacement of fluorescein-neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single drug concentration was used to examine the antibacterial activity. The structure-activity relationship data were then rapidly analyzed using a two-dimensional ribosomal binding-bacterial inhibition plot analysis. PMID:23856777

King, Ada; Watkins, Derrick; Kumar, Sunil; Ranjan, Nihar; Gong, Changjun; Whitlock, Jarred

2013-01-01

217

Antibacterial mechanisms identified through structural systems pharmacology  

PubMed Central

Background The growing discipline of structural systems pharmacology is applied prospectively in this study to predict pharmacological outcomes of antibacterial compounds in Escherichia coli K12. This work builds upon previously established methods for structural prediction of ligand binding pockets on protein molecules and utilizes and expands upon the previously developed genome scale model of metabolism integrated with protein structures (GEM-PRO) for E. coli, structurally accounting for protein complexes. Carefully selected case studies are demonstrated to display the potential for this structural systems pharmacology framework in discovery and development of antibacterial compounds. Results The prediction framework for antibacterial activity of compounds was validated for a control set of well-studied compounds, recapitulating experimentally-determined protein binding interactions and deleterious growth phenotypes resulting from these interactions. The antibacterial activity of fosfomycin, sulfathiazole, and trimethoprim were accurately predicted, and as a negative control glucose was found to have no predicted antibacterial activity. Previously uncharacterized mechanisms of action were predicted for compounds with known antibacterial properties, including (1-hydroxyheptane-1,1-diyl)bis(phosphonic acid) and cholesteryl oleate. Five candidate inhibitors were predicted for a desirable target protein without any known inhibitors, tryptophan synthase ? subunit (TrpB). In addition to the predictions presented, this effort also included significant expansion of the previously developed GEM-PRO to account for physiological assemblies of protein complex structures with activities included in the E. coli K12 metabolic network. Conclusions The structural systems pharmacology framework presented in this study was shown to be effective in the prediction of molecular mechanisms of antibacterial compounds. The study provides a promising proof of principle for such an approach to antibacterial development and raises specific molecular and systemic hypotheses about antibacterials that are amenable to experimental testing. This framework, and perhaps also the specific predictions of antibacterials, is extensible to developing antibacterial treatments for pathogenic E. coli and other bacterial pathogens. PMID:24112686

2013-01-01

218

Cloning and Structure-Function Analyses of Quinolone- and Acridone-producing Novel Type III Polyketide Synthases from Citrus microcarpa*  

PubMed Central

Two novel type III polyketide synthases, quinolone synthase (QNS) and acridone synthase (ACS), were cloned from Citrus microcarpa (Rutaceae). The deduced amino acid sequence of C. microcarpa QNS is unique, and it shared only 56–60% identities with C. microcarpa ACS, Medicago sativa chalcone synthase (CHS), and the previously reported Aegle marmelos QNS. In contrast to the quinolone- and acridone-producing A. marmelos QNS, C. microcarpa QNS produces 4-hydroxy-N-methylquinolone as the “single product” by the one-step condensation of N-methylanthraniloyl-CoA and malonyl-CoA. However, C. microcarpa ACS shows broad substrate specificities and produces not only acridone and quinolone but also chalcone, benzophenone, and phloroglucinol from 4-coumaroyl-CoA, benzoyl-CoA, and hexanoyl-CoA, respectively. Furthermore, the x-ray crystal structures of C. microcarpa QNS and ACS, solved at 2.47- and 2.35-? resolutions, respectively, revealed wide active site entrances in both enzymes. The wide active site entrances thus provide sufficient space to facilitate the binding of the bulky N-methylanthraniloyl-CoA within the catalytic centers. However, the active site cavity volume of C. microcarpa ACS (760 ?3) is almost as large as that of M. sativa CHS (750 ?3), and ACS produces acridone by employing an active site cavity and catalytic machinery similar to those of CHS. In contrast, the cavity of C. microcarpa QNS (290 ?3) is significantly smaller, which makes this enzyme produce the diketide quinolone. These results as well as mutagenesis analyses provided the first structural bases for the anthranilate-derived production of the quinolone and acridone alkaloid by type III polyketide synthases. PMID:23963450

Mori, Takahiro; Shimokawa, Yoshihiko; Matsui, Takashi; Kinjo, Keishi; Kato, Ryohei; Noguchi, Hiroshi; Sugio, Shigetoshi; Morita, Hiroyuki; Abe, Ikuro

2013-01-01

219

A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots.  

PubMed

Quinolones are synthetic antibiotics, and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, in contrast to the case for other organisms, such mutations have not been found in quinolone-resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance. SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient element that evolved over millions of years in this species. It thus seems unlikely that its main function would be resistance to quinolones, a family of synthetic antibiotics not present in natural environments until the last few decades. Expression of SmeDEF is tightly controlled by the transcriptional repressor SmeT. Our work shows that plant-produced flavonoids can bind to SmeT, releasing it from smeDEF and smeT operators. Antibiotics extruded by SmeDEF do not impede the binding of SmeT to DNA. The fact that plant-produced flavonoids specifically induce smeDEF expression indicates that they are bona fide effectors regulating expression of this resistance determinant. Expression of efflux pumps is usually downregulated unless their activity is needed. Since smeDEF expression is triggered by plant-produced flavonoids, we reasoned that this efflux pump may have a role in the colonization of plants by S. maltophilia. Our results showed that, indeed, deletion of smeE impairs S. maltophilia colonization of plant roots. Altogether, our results indicate that quinolone resistance is a recent function of SmeDEF and that colonization of plant roots is likely one original function of this efflux pump. PMID:24837376

García-León, Guillermo; Hernández, Alvaro; Hernando-Amado, Sara; Alavi, Peyman; Berg, Gabriele; Martínez, José Luis

2014-08-01

220

A Simple Fragment of Cyclic Acyldepsipeptides Is Necessary and Sufficient for ClpP Activation and Antibacterial Activity.  

PubMed

The development of new antibacterial agents, particularly those with unique biological targets, is essential to keep pace with the inevitable emergence of drug resistance in pathogenic bacteria. We identified the minimal structural component of the cyclic acyldepsipeptide (ADEP) antibiotics that exhibits antibacterial activity. We found that N-acyldifluorophenylalanine fragments function via the same mechanism of action as ADEPs, as evidenced by the requirement of ClpP for the fragments' antibacterial activity, the ability of fragments to activate Bacillus subtilis ClpP in vitro, and the capacity of an N-acyldifluorophenylalanine affinity matrix to capture ClpP from B. subtilis cell lysates. N-acyldifluorophenylalanine fragments are much simpler in structure than the full ADEPs and are also highly amenable to structural diversification. Thus, the stage has been set for the development of non-peptide activators of ClpP that can be used as antibacterial agents. PMID:25212124

Carney, Daniel W; Compton, Corey L; Schmitz, Karl R; Stevens, Julia P; Sauer, Robert T; Sello, Jason K

2014-10-13

221

Can price controls reduce pharmaceutical expenses? A case study of antibacterial expenditures in 12 Chinese hospitals from 1996 to 2005.  

PubMed

The objective of this article is to investigate whether the Chinese government's pricing policies have reduced pharmaceutical expenses. The purchasing records for systemic antibacterial drugs of 12 hospitals in Beijing from 1996 to 2005 were analyzed by separating the expenditure growth into three components: the price change, the volume change, and the structure change. Our results reveal that the structure change is the dominant determinant of drug expenditure growth. Despite lowered prices, the antibacterial drug expenditure was raised because more expensive drugs in the same therapeutic category were prescribed. It is insufficient to rely only on pricing policies to reduce drug expenses, given that physicians could circumvent the policy by prescribing more expensive drugs. In addition, physician behaviors need to be regulated to eliminate unnecessary overprescribing. PMID:23527456

Han, Sheng; Liang, Huigang; Su, Weiping; Xue, Yajiong; Shi, Luwen

2013-01-01

222

Damage to mitochondrial DNA induced by the quinolone Bay y 3118 in embryonic turkey liver.  

PubMed

Quinolones are a class of antibiotics that induce damage to and loss of DNA from bacteria. The structural organization of bacterial DNA is more similar to eukaryotic mitochondrial DNA (mtDNA) than to eukaryotic chromosomal or nuclear DNA (nDNA). Antibiotics affecting the bacterial genome may therefore preferentially damage mtDNA rather than nDNA. We investigated the effect of a quinolone on mtDNA in avian embryonic hepatocytes in ovo. The quinolone Bay y 3118 (1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl) 6-fluoro-8-chloro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride, chemical structure see Bremm et al. [K.D. Bremm, U. Petersen, K.G. Metzger, R. Endermann, In vitro evaluation of Bay-y 3118, a new full-spectrum fluoroquinolone, Chemotherapy 38 (1992) 376-387] was injected into fertilized turkey eggs 8 days before hatching at doses of 1, 3, 10 and 30 mg per egg. The embryos were removed from the eggs after 4 days and liver samples were shock frozen. Mitochondrial DNA was purified from samples of the embryonic liver. The integrity of mtDNA was investigated by electrophoresis on agarose gels with native mtDNA and with ribonuclease-treated mtDNA. Fluorescent staining of the electrophoresis gels allows the densitometric quantification of the mtDNA of the regular band at 16 kilobases (kb) and the amount of DNA fragments of irregular size (smear). The genotoxic nitrosamine nitrosodiethylamine (NDEA) has previously been shown to reduce the content of mtDNA of the regular size of 16 kb and to induce the occurrence of smaller fragments of mtDNA [H. Enzmann, C. Kühlem, E. Löser, P. Bannasch, Damage to mitochondrial DNA induced by the hepatocarcinogen, diethylnitrosamine in ovo, Mutation Res. 329 (1995) 113-120]. After exposure to 10 and 30 mg Bay y 3118, a dose-dependent induction of damage to the mtDNA was found, whereas exposure to 3 and 1 mg showed no effect. NDEA (25 mg) was used as positive control. Testing chemical compounds in the in ovo model is a simple and rapid approach for investigations on chemically induced alterations of mtDNA. PMID:10216214

Enzmann, H; Wiemann, C; Ahr, H J; Schlüter, G

1999-04-01

223

An antibacterial thiophene from Balsamorhiza sagittata.  

PubMed

Balsamorhiza sagittata, a species of ethnopharmacological interest in British Columbia, is reported to have antibacterial and antifungal properties. An antibacterial compound isolated from this species was identified as 7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol based on the HMQC and HMBC experiments. PMID:8720391

Matsuura, H; Saxena, G; Farmer, S W; Hancock, R E; Towers, G H

1996-02-01

224

Antibacterial activity of leaf extracts of Baeckea frutescens against methicillin-resistant Staphylococcus aureus.  

PubMed

This study was based on screening antibacterial activity of the ethanol extract of Baeckea frutescens L. against MRSA clinical isolates, analyzes the potential antibacterial compound, and assesses the cytotoxicity effect of the extract in tissue culture. Leaves of Baeckea frutescens L. were shade dried, powdered, and extracted using solvent ethanol. Preliminary phytochemical screening of the crude extracts revealed the presence of alkaloids, flavonoids, steroids, terpenoids, phenols, and carbohydrates. The presence of these bioactive constituents is related to the antibacterial activity of the plant. Disc diffusion method revealed a high degree of activity against microorganisms. The results confirm that Baeckea frutescens L. can be used as a source of drugs to fight infections caused by susceptible bacteria. PMID:25028658

Razmavar, Somayeh; Abdulla, Mahmood Ameen; Ismail, Salmah Binti; Hassandarvish, Pouya

2014-01-01

225

Proteolytically activated anti-bacterial hydrogel microspheres.  

PubMed

Hydrogels are finding increased clinical utility as advances continue to exploit their favorable material properties. Hydrogels can be adapted for many applications, including surface coatings and drug delivery. Anti-infectious surfaces and delivery systems that actively destroy invading organisms are alternative ways to exploit the favorable material properties offered by hydrogels. Sterilization techniques are commonly employed to ensure the materials are non-infectious upon placement, but sterilization is not absolute and infections are still expected. Natural, anti-bacterial proteins have been discovered which have the potential to act as anti-infectious agents; however, the proteins are toxic and need localized release to have therapeutic efficacy without toxicity. In these studies, we explore the use of the glutathione s-transferase (GST) to anchor the bactericidal peptide, melittin, to the surface of poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We show that therapeutic levels of protein can be anchored to the surface of the microspheres using the GST anchor. We compared the therapeutic efficacy of recombinant melittin released from PEGDA microspheres to melittin. We found that, when released by an activating enzyme, thrombin, recombinant melittin efficiently inhibits growth of the pathogenic bacterium Streptococcus pyogenes as effectively as melittin created by solid phase peptide synthesis. We conclude that a GST protein anchor can be used to immobilize functional protein to PEGDA microspheres and the protein will remain immobilized under physiological conditions until the protein is enzymatically released. PMID:23816641

Buhrman, Jason S; Cook, Laura C; Rayahin, Jamie E; Federle, Michael J; Gemeinhart, Richard A

2013-11-10

226

Antibacterial activity of baking soda.  

PubMed

The antibacterial activity of baking soda (sodium bicarbonate) was assessed using three different experimental approaches. Standard minimum inhibitory concentration analyses revealed substantial inhibitory activity against Streptococcus mutans that was not due to ionic strength or high osmolarity. Short-term exposure assays showed significant killing of bacterial suspensions when baking soda was combined with the detergent sodium dodecylsulfate. Multiple, brief exposures of sucrose-colonized S mutans to baking soda and sodium dodecylsulfate caused statistically significant decreases in numbers of viable cells. Use of oral health care products with high concentrations of baking soda could conceivably result in decreased levels of cariogenic S mutans in saliva and plaque. PMID:12017929

Drake, D

1997-01-01

227

Antibacterial activity of baking soda.  

PubMed

The antibacterial activity of baking soda (sodium bicarbonate) was assessed using three different experimental approaches. Standard minimum inhibitory concentration analyses revealed substantial inhibitory activity against Streptococcus mutans that was not due to ionic strength or high osmolarity. Short-term exposure assays showed significant killing of bacterial suspensions when baking soda was combined with the detergent sodium dodecylsulfate. Multiple, brief exposures of sucrose-colonized S mutans to baking soda and sodium dodecylsulfate caused statistically significant decreases in numbers of viable cells. Use of oral health care products with high concentrations of baking soda could conceivably result in decreased levels of cariogenic S mutans in saliva and plaque. PMID:11524862

Drake, D

1996-01-01

228

21 CFR 250.250 - Hexachlorophene, as a component of drug and cosmetic products.  

Code of Federal Regulations, 2013 CFR

...Section 250.250 Food and Drugs FOOD AND DRUG ADMINISTRATION...antibacterial component in drug and cosmetic...antimicrobial ingredients, including...procedures set forth in the Federal Register...potential for harmful effect, drugs... (2) The Food and Drug...

2013-04-01

229

21 CFR 250.250 - Hexachlorophene, as a component of drug and cosmetic products.  

Code of Federal Regulations, 2012 CFR

...Section 250.250 Food and Drugs FOOD AND DRUG ADMINISTRATION...antibacterial component in drug and cosmetic...antimicrobial ingredients, including...procedures set forth in the Federal Register...potential for harmful effect, drugs... (2) The Food and Drug...

2012-04-01

230

21 CFR 250.250 - Hexachlorophene, as a component of drug and cosmetic products.  

Code of Federal Regulations, 2011 CFR

...Section 250.250 Food and Drugs FOOD AND DRUG ADMINISTRATION...antibacterial component in drug and cosmetic...antimicrobial ingredients, including...procedures set forth in the Federal Register...potential for harmful effect, drugs... (2) The Food and Drug...

2011-04-01

231

In vitro antibacterial effect of wasp (Vespa orientalis) venom  

PubMed Central

Background The emergence of antibacterial resistance against several classes of antibiotics is an inevitable consequence of drug overuse. As antimicrobial resistance spreads throughout the globe, new substances will always be necessary to fight against multidrug-resistant microorganisms. Venoms of many animals have recently gained attention in the search for new antimicrobials to treat infectious diseases. Thefore, the present study aimed to study the antibacterial effects of wasp (Vespa orientalis) crude venom. Two gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two gram-negative ones (Escherichia coli and Klesiella pneumonia) were compared for their sensitivity to the venom by determining the inhibition zone (Kirby-Bauer method) and minimum inhibitory concentration (MIC). A microbroth kinetic system based on continuous monitoring of changes in the optical density of bacterial growth was also used for determination of antimicrobial activity. Results The venom exhibited a well-recognized antimicrobial property against the tested bacterial strains. The inhibition zones were determined to be 12.6, 22.7, 22.4 and 10.2 mm for S. aureus, B. subtilis, E. coli and K. pneumonia, respectively. The corresponding MIC values were determined to be 64, 8, 64 and 128 ?g/mL, respectively. The MIC50 and MIC90 values of the venom were respectively determined to be 63.6 and 107 ?g/mL for S. aureus, 4.3 and 7.0 ?g/mL for B. subtilis, 45.3 and 65.7 ?g/mL for E. coli and 74.4 and 119.2 ?g/mL for K. pneumonia. Gram-positive bacteria were generally more sensitive to the venom than gram-negative ones. Conclusions Results revealed that the venom markedly inhibits the growth of both gram-positive and gram-negative bacteria and could be considered a potential source for developing new antibacterial drugs. PMID:24955088

2014-01-01

232

4-Quinolones as Noncovalent Inhibitors of High Molecular Mass Penicillin-Binding Proteins  

PubMed Central

Penicillin-binding proteins (PBPs) are important bacterial enzymes that carry out the final steps of bacterial cell wall assembly. Their DD-transpeptidase activity accomplishes the essential peptide cross-linking step of the cell wall. To date, all attempts to discover effective inhibitors of PBPs, apart from ?-lactams, have not led to new antibiotics. Therefore, the need for new classes of efficient inhibitors of these enzymes remains. Guided by a computational fragment-based docking procedure, carried out on Escherichia coli PBP5, we have designed and synthesized a series of 4-quinolones as potential inhibitors of PBPs. We describe their binding to the PBPs of E. coli and Bacillus subtilis. Notably, these compounds bind quite tightly to the essential high molecular mass PBPs. PMID:24900515

2012-01-01

233

Elimination of quinolone antibiotic carryover through use of antibiotic-removal beads.  

PubMed Central

To prove the utility of antibiotic-removal beads in separating antibiotics from bacterial samples, Escherichia coli ATCC 25922 was exposed to five separate quinolones before and after each was exposed to antibiotic-removal beads. Plates treated with antibiotic solutions that were exposed to beads demonstrated antibiotic removal, and plates treated with antibiotic solutions that were not exposed to beads demonstrated antibiotic carryover. After exposure to beads, fluoroquinolone concentrations decreased from 5 micrograms/ml to 0.14 micrograms/ml (ciprofloxacin), 0.04 micrograms/ml (temafloxacin), < 0.01 microgram/ml (ofloxacin), < 0.01 microgram/ml (sparfloxacin), and 0.02 micrograms/ml (clinafloxacin). These data indicate that antibiotic carryover can be successfully circumvented through the use of antibiotic-removal beads. Images PMID:8328791

Zabinski, R A; Larsson, A J; Walker, K J; Gilliland, S S; Rotschafer, J C

1993-01-01

234

Random Mutagenesis of the Aspergillus oryzae Genome Results in Fungal Antibacterial Activity.  

PubMed

Multidrug-resistant bacteria cause severe infections in hospitals and communities. Development of new drugs to combat resistant microorganisms is needed. Natural products of microbial origin are the source of most currently available antibiotics. We hypothesized that random mutagenesis of Aspergillus oryzae would result in secretion of antibacterial compounds. To address this hypothesis, we developed a screen to identify individual A. oryzae mutants that inhibit the growth of Methicillin-resistant Staphylococcus aureus (MRSA) in vitro. To randomly generate A. oryzae mutant strains, spores were treated with ethyl methanesulfonate (EMS). Over 3000 EMS-treated A. oryzae cultures were tested in the screen, and one isolate, CAL220, exhibited altered morphology and antibacterial activity. Culture supernatant from this isolate showed antibacterial activity against Methicillin-sensitive Staphylococcus aureus, MRSA, and Pseudomonas aeruginosa, but not Klebsiella pneumonia or Proteus vulgaris. The results of this study support our hypothesis and suggest that the screen used is sufficient and appropriate to detect secreted antibacterial fungal compounds resulting from mutagenesis of A. oryzae. Because the genome of A. oryzae has been sequenced and systems are available for genetic transformation of this organism, targeted as well as random mutations may be introduced to facilitate the discovery of novel antibacterial compounds using this system. PMID:23983696

Leonard, Cory A; Brown, Stacy D; Hayman, J Russell

2013-01-01

235

Toxicity and antibacterial assessment of chitosancoated silver nanoparticles on human pathogens and macrophage cells  

PubMed Central

Background Pathogenic bacteria are able to develop various strategies to counteract the bactericidal action of antibiotics. Silver nanoparticles (AgNPs) have emerged as a potential alternative to conventional antibiotics because of their potent antimicrobial properties. The purpose of this study was to synthesize chitosan-stabilized AgNPs (CS-AgNPs) and test for their cytotoxic, genotoxic, macrophage cell uptake, antibacterial, and antibiofilm activities. Methods AgNPs were synthesized using chitosan as both a stabilizing and a reducing agent. Antibacterial activity was determined by colony-forming unit assay and scanning electron microscopy. Genotoxic and cytotoxic activity were determined by DNA fragmentation, comet, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Cellular uptake and intracellular antibacterial activity were tested on macrophages. Results CS-AgNPs exhibited potent antibacterial activity against different human pathogens and also impeded bacterial biofilm formation. Scanning electron microscopy analysis indicated that CS-AgNPs kill bacteria by disrupting the cell membrane. CS-AgNPs showed no significant cytotoxic or DNA damage effect on macrophages at the bactericidal dose. Propidium iodide staining indicated active endocytosis of CS-AgNPs resulting in reduced intracellular bacterial survival in macrophages. Conclusion The present study concludes that at a specific dose, chitosan-based AgNPs kill bacteria without harming the host cells, thus representing a potential template for the design of antibacterial agents to decrease bacterial colonization and to overcome the problem of drug resistance. PMID:22619529

Jena, Prajna; Mohanty, Soumitra; Mallick, Rojee; Jacob, Biju; Sonawane, Avinash

2012-01-01

236

Antibacterial activity of dentine primer containing MDPB after curing  

Microsoft Academic Search

Objectives: A monomer methacryloyloxydodecylpyridinium bromide (MDPB) has antibacterial activity before polymerization. Furthermore, the antibacterial agent is immobilized by the polymerization of MDPB and the resin-based material incorporating MDPB is able to show an antibacterial effect even after being cured. The purpose of this study was to investigate the antibacterial effect of a dentine primer containing MDPB after curing.Methods: The inhibitory

S. Imazato; A. Ehara; M. Torii; S. Ebisu

1998-01-01

237

A conserved suppressor mutation in a tryptophan auxotroph results in dysregulation of Pseudomonas quinolone signal synthesis.  

PubMed

Pseudomonas aeruginosa is a common nosocomial pathogen that relies on three cell-to-cell signals to regulate multiple virulence factors. The Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone) is one of these signals, and it is known to be important for P. aeruginosa pathogenesis. PQS is synthesized in a multistep reaction that condenses anthranilate and a fatty acid. In P. aeruginosa, anthranilate is produced via the kynurenine pathway and two separate anthranilate synthases, TrpEG and PhnAB, the latter of which is important for PQS synthesis. Others have previously shown that a P. aeruginosa tryptophan auxotroph could grow on tryptophan-depleted medium with a frequency of 10(-5) to 10(-6). These revertants produced more pyocyanin and had increased levels of phnA transcript. In this study, we constructed similar tryptophan auxotroph revertants and found that the reversion resulted from a synonymous G-to-A nucleotide mutation within pqsC. This change resulted in increased pyocyanin and decreased PQS, along with an increase in the level of the pqsD, pqsE, and phnAB transcripts. Reporter fusion and reverse transcriptase PCR studies indicated that a novel transcript containing pqsD, pqsE, and phnAB occurs in these revertants, and quantitative real-time PCR experiments suggested that the same transcript appears in the wild-type strain under nutrient-limiting conditions. These results imply that the PQS biosynthetic operon can produce an internal transcript that increases anthranilate production and greatly elevates the expression of the PQS signal response protein PqsE. This suggests a novel mechanism to ensure the production of both anthranilate and PQS-controlled virulence factors. PMID:24748618

Knoten, Claire A; Wells, Greg; Coleman, James P; Pesci, Everett C

2014-07-01

238

Overcoming scientific and structural bottlenecks in antibacterial discovery and development  

PubMed Central

Antibiotic resistance is becoming an increasing threat, with too few novel antibiotics coming to market to replace those lost due to resistance development. Efforts by the pharmaceutical industry to screen for and design novel antibacterials have not been successful, with several companies minimizing or closing down their antibacterial research units, leading to a loss of skills and know-how. At the same time, antibiotic innovation in academia is not filling the void due to misaligned incentive structures and lack of vital knowledge of drug discovery. The scientific and structural difficulties in discovering new antibiotics have only begun to be appreciated in the latest years. Part of the problem has been a paradigm shift within both industry and academia to focus on ‘rational’ drug development with an emphasis on single targets and high-throughput screening of large chemical libraries, which may not be suited to target bacteria. The very particular aspects of ‘targeting an organism inside another organism’ have not been given enough attention. In this paper, researcher interviews have complemented literature studies to delve deeper into the specifics of the different scientific and structural barriers, and some potential solutions are offered. PMID:24646118

2014-01-01

239

Overcoming scientific and structural bottlenecks in antibacterial discovery and development.  

PubMed

Antibiotic resistance is becoming an increasing threat, with too few novel antibiotics coming to market to replace those lost due to resistance development. Efforts by the pharmaceutical industry to screen for and design novel antibacterials have not been successful, with several companies minimizing or closing down their antibacterial research units, leading to a loss of skills and know-how. At the same time, antibiotic innovation in academia is not filling the void due to misaligned incentive structures and lack of vital knowledge of drug discovery. The scientific and structural difficulties in discovering new antibiotics have only begun to be appreciated in the latest years. Part of the problem has been a paradigm shift within both industry and academia to focus on 'rational' drug development with an emphasis on single targets and high-throughput screening of large chemical libraries, which may not be suited to target bacteria. The very particular aspects of 'targeting an organism inside another organism' have not been given enough attention. In this paper, researcher interviews have complemented literature studies to delve deeper into the specifics of the different scientific and structural barriers, and some potential solutions are offered. PMID:24646118

Zorzet, Anna

2014-05-01

240

The simultaneous separation and determination of five quinolone antibotics using isocratic reversed-phase HPLC: Application to stability studies on an ofloxacin tablet formulation  

Microsoft Academic Search

A rapid and reliable HPLC method was developed for the simultaneously separation and quantitation of five quinolones antibiotics; nalidixic acid, norfloxacin, ofloxacin, ciprofloxacin and lomefloxacin. All five tablet formulations of individual quinolone antibiotics were routinely assayed without interference. The calibration curves were linear (r2?0.999) over the concentration range of 1.20–4.8mg\\/100ml. Selectivity, precision, sensitivity and accuracy were established and the method

Leroy A. Shervington; Michael Abba; Bushra Hussain; James Donnelly

2005-01-01

241

The tip of the iceberg: quinolone-resistance conferred by mutations in gyrA gene in non-typhoidal Salmonella strains.  

PubMed

Food-borne infections due to Salmonella spp. seldom require antimicrobial therapy, but this is compulsory in systemic salmonellosis. Salmonella resistance to a large panel of antibiotics has been described worldwide. Since the introduction of nalidixic acid in therapy, Salmonella spp. have steadily developed resistance, especially over the last three decades. The source of quinolone resistance is thought to be the selective pressure determined by the use of quinolones in both human and veterinary practices. Resistance acquisition of Salmonella strains is a stepwise process. Several mechanisms are described, which can lead to the development of quinolone resistance. The main mechanism is considered to be linked with mutations in the quinolone-resistance determining region (QRDR) of the target genes (gyrA and gyrB encoding DNA gyrase, and parC and parE encoding topoisomerase IV). This first step in mutational resistance usually determines a rise in the nalidixic acid minimal inhibitory concentration (MIC). The most common amino acid substitutions in the GyrA subunit, resulting in varied degrees of quinolone resistance, occur at codons Ser83 and Asp87. Higher levels of resistance may occur by further mutational steps, with amino acid changes in the same or a different target enzyme. Other mechanisms are as well involved, like increased efflux or plasmid-mediated resistance. Acknowledgement of the epidemiology and the onset mechanisms of quinolone resistance in Salmonella spp. is compulsory, and surveillance for resistant bacteria among human, animal and food sources remains critical. PMID:22838215

N??cu?iu, Alexandra-Maria

2012-01-01

242

Stimuli-responsive self-assembling peptides made from antibacterial peptides  

NASA Astrophysics Data System (ADS)

How to use bioactive peptide sequences as fundamental building blocks to make hydrogel materials which are stimuli-responsive? In this article, we provide a novel designed peptide comprising two antibacterial peptide sequences (KIGAKI)3-NH2 and a central tetrapeptide linker. Results show that balancing the forces of the electrostatic repulsion of the charged lysine residues against the hydrophobic collapse of the isoleucine and alanine residues and backbone ?-sheet hydrogen bonding allows the structural transition and formation of individually dispersed nanofibers. Circular Dichroism (CD) and rheology analysis demonstrated that the designed peptide can undergo an abrupt structural transition from a random coil to a stable unimolecular ?-hairpin conformation and subsequently form an elastic hydrogel when exposed to external stimuli such as pH, ionic strength and heat. The assembly kinetics of the obtained antibacterial sequence comprising peptide (ASCP) was studied by time-lapse Atomic Force Microscopy (AFM) and Thioflavin T (ThT) binding assay. In addition, the inherent antibacterial activity of the peptide hydrogel was confirmed by the antibacterial assay against Escherichia coli. This example described epitomizes the use of bioactive peptide sequences in the design of finite self-assembled structures with potential inherent activity. These hydrogel materials may find applications in drug delivery, tissue engineering and regenerative medicine.How to use bioactive peptide sequences as fundamental building blocks to make hydrogel materials which are stimuli-responsive? In this article, we provide a novel designed peptide comprising two antibacterial peptide sequences (KIGAKI)3-NH2 and a central tetrapeptide linker. Results show that balancing the forces of the electrostatic repulsion of the charged lysine residues against the hydrophobic collapse of the isoleucine and alanine residues and backbone ?-sheet hydrogen bonding allows the structural transition and formation of individually dispersed nanofibers. Circular Dichroism (CD) and rheology analysis demonstrated that the designed peptide can undergo an abrupt structural transition from a random coil to a stable unimolecular ?-hairpin conformation and subsequently form an elastic hydrogel when exposed to external stimuli such as pH, ionic strength and heat. The assembly kinetics of the obtained antibacterial sequence comprising peptide (ASCP) was studied by time-lapse Atomic Force Microscopy (AFM) and Thioflavin T (ThT) binding assay. In addition, the inherent antibacterial activity of the peptide hydrogel was confirmed by the antibacterial assay against Escherichia coli. This example described epitomizes the use of bioactive peptide sequences in the design of finite self-assembled structures with potential inherent activity. These hydrogel materials may find applications in drug delivery, tissue engineering and regenerative medicine. Electronic supplementary information (ESI) available: Fig. S1-S5. See DOI: 10.1039/c3nr00225j

Liu, Yanfei; Yang, Yanlian; Wang, Chen; Zhao, Xiaojun

2013-06-01

243

Solidphase synthesis and antibacterial activity of hydroxycinnamic acid amides and analogues against methicillin-resistant Staphylococcus aureus and vancomycin-resistant S. aureus  

Microsoft Academic Search

A library of hydroxycinnamic acid amides (HCAAs) and analogues were synthesized using solid-phase synthesis technique. These compounds were screened for antibacterial against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Dihydrocaffeoyl analogues showed activity against VRSA which were better than the reference drugs, vancomycin and oxacillin. These compounds also exhibited antibacterial activity against MRSA, which

Boon-ek Yingyongnarongkul; Nuttapon Apiratikul; Nuntana Aroonrerk; Apichart Suksamrarn

2006-01-01

244

Atanine (3-dimethylallyl-4-methoxy-2-quinolone), an alkaloid with anthelmintic activity from the Chinese medicinal plant, Evodia rutaecarpa.  

PubMed

Phytochemical studies using a range of chromatographic and spectroscopic techniques coupled with in vitro bioassays against larval Schistosoma mansoni, L4 larvae of Ostertagia circumcincta, and adults and larvae of Caenorhabditis elegans have led to the isolation of an active anthelmintic compound in the Chinese medicinal plant Evodia rutaecarpa (Rutaceae) and its identification as atanine (3-dimethylallyl-4-methoxy-2-quinolone). Atanine has not previously been found to possess antiparasitic activity. PMID:7617774

Perrett, S; Whitfield, P J

1995-06-01

245

Phylogenetic groups, virulence genes and quinolone resistance of integron-bearing Escherichia coli strains isolated from a wastewater treatment plant  

Microsoft Academic Search

We investigated phylogenetic affiliation, occurrence of virulence genes and quinolone resistance in 109 integron-containing\\u000a strains of Escherichia coli isolated from a wastewater treatment plant. Selection for integron-bearing strains caused a shift toward phylogroup D, which\\u000a was most numerous, followed by A, B1 and B2. Phylogroups D and B2, both of which are reported to include virulent extraintestinal\\u000a pathotypes, made up

Joanna Mokracka; Ryszard Koczura; Lucyna Jab?o?ska; Adam Kaznowski

2011-01-01

246

Ion-pairing and reversed phase liquid chromatography for the determination of three different quinolones: Enrofloxacin, lomefloxacin and ofloxacin  

Microsoft Academic Search

Two simple and sensitive high performance liquid chromatographic (HPLC) methods have been developed for the simultaneous determination of three different quinolones: enrofloxacin, lomefloxacin and ofloxacin in their pure and dosage forms, one with reversed phase HPLC and the other with ion-pair HPLC. In reversed phase HPLC, method (A), the mobile phase consists of 2.18% aqueous solution of KH2PO4 with pH

Alaa S. Amin; Hassan A. Dessouki; Ibrahim A. Agwa

2011-01-01

247

High Resolution Melting Analysis for Rapid Mutation Screening in Gyrase and Topoisomerase IV Genes in Quinolone-Resistant Salmonella enterica  

PubMed Central

The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM) assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR) of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (n = 52; S83F, S83Y, S83I, D87G, D87Y, and D87N) and parE (n = 1; M438I). Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC 16 > 256??g/mL). Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes. PMID:25371903

Thong, Kwai Lin

2014-01-01

248

Antibacterial polymeric nanostructures for biomedical applications.  

PubMed

The high incidence of bacterial infection and the growing resistance of bacteria to conventional antibiotics have resulted in the strong need for the development of new generation of antibiotics. Nano-sized particles have been considered as novel antibacterial agents with high surface area and high reactivity. The overall antibacterial properties of antimicrobial nanostructures can be significantly enhanced compared with conventional antibacterial agents not in a regular nanostructure, showing a better effect in inhibiting the growth and reproduction of microbials such as bacteria and fungi, etc. In this review, recent advances in the research and applications of antimicrobial polymeric nanostructures have been highlighted, including silver-decorated polymer micelles and vesicles, antimicrobial polymer micelles and vesicles, and antimicrobial peptide-based vesicles, etc. Furthermore, we proposed the current challenges and future research directions in the field of antibacterial polymeric nanostructures for the real-world biomedical applications. PMID:25110921

Chen, Jing; Wang, Fangyingkai; Liu, Qiuming; Du, Jianzhong

2014-12-01

249

Antiadhesive and Antibacterial Coatings for Biofouling Control  

E-print Network

silver nanomaterials have found their way to many commercially available products such as households water filters,silver nanoparticles have been incorporated, as an antibacterial agent, into a number of products such as households water filters,

Marambio Jones, Catalina Stephanie

2014-01-01

250

Antibacterial Effect of Some Azaphenanthrene Compounds  

PubMed Central

Five newly synthesized azaphenanthrene compounds have been studied for their antibacterial activity, which to varying degrees was shown to be related to the position of the aza, methyl, and benzyl groups in the ring. PMID:5456010

Gupta, K. G.; Kessar, S. V.; Singh, Baldev

1970-01-01

251

Some nitroimidazole derivatives as possible antibacterial agents.  

PubMed

In this study, six 1-[2(benzazol-2-yl)thioethyl]-2-methyl-5- nitroimidazole derivatives were synthesized. Antibacterial activities of the compounds obtained were examined and it was found that they are effective against aerobe bacteria. PMID:8323675

Demirayak, S; Kiraz, N

1993-03-01

252

drug discovery drug discovery  

E-print Network

drug discovery at Purdue #12;drug discovery 2 #12;drug discovery 3 Introduction The drug discovery and innovative drug candidates to treat chronic and acute illnesses. Our researchers also continue to be invested in various approaches to drug discovery, which include understanding of drug targets for future drug

253

Antibacterial activity of some Indian medicinal plants  

Microsoft Academic Search

Aqueous extracts of ten medicinal plants were examined for their antibacterial potential against some reference strains of\\u000a human pathogenic bacteria. Anethum graveolens, Elettaria cardamomum, Foeniculum vulgare, Trachyspermum ammi and Viola odorata were found to be better\\/equally effective compared to standard antibiotics. V. odorata was the most effective antibacterial with minimum inhibitory concentration values ranging from 1 to 2%. The results

Daljit Singh Arora; Gurinder Jeet Kaur

2007-01-01

254

NB2001, a Novel Antibacterial Agent with Broad-Spectrum Activity and Enhanced Potency against  -Lactamase-Producing Strains  

Microsoft Academic Search

Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to overcome drug resistance resulting from enzyme overexpression. -Lactamase overexpression is a common mechanism of bacterial resistance to -lactam antibiotics. We present here the results for one of the -lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold. Unlike conventional -lactam

Qing Li; Jean Y. Lee; Rosario Castillo; Mark S. Hixon; Catherine Pujol; Venkata Ramana Doppalapudi; H. Michael Shepard; Geoffrey M. Wahl; Thomas J. Lobl; Ming Fai Chan

2002-01-01

255

The Cyclic Cystine Ladder in ?-Defensins Is Important for Structure and Stability, but Not Antibacterial Activity*  

PubMed Central

?-Defensins are ribosomally synthesized cyclic peptides found in the leukocytes of some primate species and have promising applications as antimicrobial agents and scaffolds for peptide drugs. The cyclic cystine ladder motif, comprising a cyclic peptide backbone and three parallel disulfide bonds, is characteristic of ?-defensins. In this study, we explore the role of the cyclic peptide backbone and cystine ladder in the structure, stability, and activity of ?-defensins. ?-Defensin analogues with different numbers and combinations of disulfide bonds were synthesized and characterized in terms of their NMR solution structures, serum and thermal stabilities, and their antibacterial and membrane-binding activities. Whereas the structures and stabilities of the peptides were primarily dependent on the number and position of the disulfide bonds, their antibacterial and membrane-binding properties were dependent on the cyclic backbone. The results provide insights into the mechanism of action of ?-defensins and illustrate the potential of ?-defensin analogues as scaffolds for peptide drug design. PMID:23430740

Conibear, Anne C.; Rosengren, K. Johan; Daly, Norelle L.; Henriques, Sonia Troeira; Craik, David J.

2013-01-01

256

Antibacterial studies, DNA oxidative cleavage, and crystal structures of Cu(II) and Co(II) complexes with two quinolone family members, ciprofloxacin and enoxacin  

Microsoft Academic Search

Nine coordination compounds of Cu(II) and Co(II) with Ciprofloxacin (HCp) and Enoxacin (HEx) as ligands have been prepared and characterized. Single crystal structural determinations of [Cu(HCp)2(ClO4)2]·6H2O (1) and [Co(HEx)2(Ex)]Cl·2CH3OH·12H2O (4) are reported. The crystal of 1 is composed of [Cu(HCp)2(ClO4)2] units with the two perchlorate anions semicoordinated, and uncoordinated water molecules. The copper ion, at a crystallographic inversion centre, is

N. Jiménez-Garrido; L. Perelló; R. Ortiz; G. Alzuet; M. González-Álvarez; E. Cantón; M. Liu-González; S. García-Granda; M. Pérez-Priede

2005-01-01

257

Multiaction antibacterial nanofibrous membranes fabricated by electrospinning: an excellent system for antibacterial applications  

NASA Astrophysics Data System (ADS)

In this paper, novel multiaction antibacterial nanofibrous membranes containing apatite, Ag, AgBr and TiO2 as four active components were fabricated by an electrospinning technique. In this antibacterial membrane, each component serves a different function: the hydroxyapatite acts as the adsorption material for capturing bacteria, the Ag nanoparticles act as the release-active antibacterial agent, the AgBr nanoparticles act as the visible sensitive and release-active antibacterial agent, and the TiO2 acts as the UV sensitive antibacterial material and substrate for other functional components. Using E. coli as the typical testing organism, such multicomponent membranes exhibit excellent antimicrobial activity under UV light, visible light or in a dark environment. The significant antibacterial properties may be due to the synergetic action of the four major functional components, and the unique porous structure and high surface area of the nanofibrous membrane. It takes only 20 min for the bacteria to be completely (99.9%) destroyed under visible light. Even in a dark environment, about 50 min is enough to kill all of the bacteria. Compared to the four component system in powder form reported previously, the addition of the electrospun membrane could significantly improve the antibacterial inactivation of E. coli under the same evaluation conditions. Besides the superior antimicrobial capability, the permanence of the antibacterial activity of the prepared free-standing membranes was also demonstrated in repeated applications.

Wu, Yiguang; Jia, Weijie; An, Qi; Liu, Yuanfeng; Chen, Jinchun; Li, Guangtao

2009-06-01

258

Supramolecular photochemistry of drugs in biomolecular environments.  

PubMed

In this tutorial review we illustrate how the interaction of photoactive drugs/potential drugs with proteins or DNA in supramolecular complexes can determine the course of the reactions initiated by the drug absorbed photons, evidencing the mechanistic differences with respect to the solution conditions. We focus on photoprocesses, independent of oxygen, that lead to chemical modification of the biomolecules, with formation of new covalent bonds or cleavage of existing bonds. Representative systems are mainly selected from the literature of the last decade. The photoreactivity of some aryl propionic acids, (fluoro)quinolones, furocoumarins, metal coordination complexes, quinine-like compounds, naphthaleneimides and pyrenyl-peptides with proteins or DNA is discussed. The use of light for biomolecule photomodification, historically relevant to biological photosensitization processes and some forms of photochemotherapy, is nowadays becoming more and more important in the development of innovative methods in nanomedicine and biotechnology. PMID:24464275

Monti, Sandra; Manet, Ilse

2014-06-21

259

Bacteriophages as twenty-first century antibacterial tools for food and medicine  

Microsoft Academic Search

Antibiotic-resistant bacteria are an increasing source of concern in all environments in which these drugs have been used.\\u000a More stringent regulations have led to a slow but sure decrease in antibiotic use in the food industry worldwide, but have\\u000a also stimulated the search for alternative antibacterial agents. In medicine, the number of people infected with pan-resistant\\u000a bacteria is driving research

Damien Maura; Laurent Debarbieux

2011-01-01

260

Antibacterial activity of cefquinome against equine bacterial pathogens.  

PubMed

Cefquinome is known for its use as an antibacterial drug in cattle and pigs. The objective of this study was to evaluate the antibacterial activity of cefquinome against equine pathogenic bacteria. The minimum inhibitory concentration (MIC) of cefquinome was determined for a total of 205 strains, which had recently been isolated in Europe from diseased horses (respiratory infection, foal septicaemia). The bactericidal activity was tested against 19 strains using the time killing method. The post-antibiotic effect (PAE) and post-antibiotic sub-MIC effect (PA SME) were determined against 12 strains. Cefquinome showed high activity against Actinobacillus equuli and streptococci (MIC(90) of 0.016 and 0.032microg/mL), Enterobacteriaceae (MIC(90)=0.125microg/mL) and staphylococci (MIC(90)=0.5microg/mL). The activity was limited against Rhodococcus spp. and Pseudomonas spp. Cefquinome was shown to be a time dependent bactericidal antibiotic against the target pathogens, killing occurring at a concentration close to the MIC. A PAE of 0.5-10h was calculated against streptococci whereas no PAE was observed for Escherichia coli. A longer PA SME was determined for streptococci (3.3 to >24h with a killing effect) and E. coli (0.5-13.9h). Cefquinome was shown to have a broad spectrum of activity which covers many equine pathogens. PMID:16455213

Thomas, E; Thomas, V; Wilhelm, C

2006-06-15

261

In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives with a 2-thienyl group.  

PubMed

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization. PMID:17507195

Pardakhty, Abbas; Foroumadi, Alireza; Hashemi, Mehdi; Rajabalian, Saeed; Heidari, Mahmoud Reza

2007-09-01

262

Conformational analysis of a quinolonic ribonucleoside with anti-HSV-1 activity  

NASA Astrophysics Data System (ADS)

The infections caused by the Herpes Simplex Virus are one of the most common sources of diseases in adults and several natural nucleoside analogues are currently used in the treatment of these infections. In vitro tests of a series of quinolonic ribonucleosides derivatives synthesized by part of our group indicated that some of them have antiviral activity against HSV-1. The conformational analysis of bioactive compounds is extremely important in order to better understand their chemical structures and biological activity. In this work, we have carried out a nuclear relaxation NMR study of 6-Me ribonucleoside derivative in order to determine if the syn or anti conformation is preferential. The NMR analysis permits the determination of inter-atomic distances by using techniques which are based on nuclear relaxation and related phenomena. Those techniques are non-selective longitudinal or spin-lattice relaxation rates and NULL pulse sequence, which allow the determination of distances between pairs of hydrogen atoms. The results of NMR studies were compared with those obtained by molecular modeling.

Yoneda, Julliane D.; Velloso, Marcia Helena R.; Leal, Kátia Z.; Azeredo, Rodrigo B. de V.; Sugiura, Makiko; Albuquerque, Magaly G.; Santos, Fernanda da C.; Souza, Maria Cecília B. V. de; Cunha, Anna Claudia; Seidl, Peter R.; Alencastro, Ricardo B. de; Ferreira, Vitor F.

2011-01-01

263

A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity.  

PubMed

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G; McAdam, Alexander J; Husson, Robert N; Tamayo, Giselle; Clardy, Jon; Watnick, Paula I

2012-01-01

264

A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity  

PubMed Central

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G.; McAdam, Alexander J.; Husson, Robert N.; Tamayo, Giselle; Clardy, Jon; Watnick, Paula I.

2012-01-01

265

Purification, characterization and antibacterial activity of L-amino acid oxidase from Cerastes cerastes.  

PubMed

Antibiotic resistance presents a real problem in which new antibacterial molecules from natural secretions could be beneficial in the development of new drugs. In this study, Cerastes cerastes venom was investigated for its antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity was evaluated by measuring the halo inhibition and minimum inhibitory concentration (MIC). An L-amino acid oxidase (CcLAAO) was purified from this venom using three chromatographic steps; its homogeneity (60 kDa) was confirmed by SDS-PAGE. LC-MS/MS analysis of CcLAAO showed similarities with other LAAO enzymes from Echis ocellatus and Viridovipera stejnegeri venoms. CcLAAO presents an antibacterial activity against three bacterial strains (Staphylococcus aureus, Methicillin-resistant S. aureus, and Pseudomonas aeruginosa) with MIC values of 10, 10, and 20 ?g/mL, respectively. However, no effect was observed against Escherichia coli and yeast strains. Kinetic parameters of CcLAAO evaluated on L-leucine at pH 8.0 and 20°C were Km = 0.06 mmol and Vmax = 164 mmol/min. PMID:24817275

Hanane-Fadila, Ziad-Meziane; Fatima, Laraba-Djebari

2014-08-01

266

Effect of antibacterials on biofilms.  

PubMed

Indwelling catheters are the most common cause of health care-associated bloodstream infections (BSIs). BSIs arise from a bacterial biofilm that consists of bacteria embedded within an extracellular polysaccharide matrix on the catheter surface. The initial step in biofilm formation is adherence of planktonic organisms to the catheter surface. Attached organisms divide to form microcolonies and secrete an extracellular polysaccharide matrix. Under stress conditions, these organisms can detach and become planktonic, resulting in bacteremia that can allow the bacteria to colonize a new site. Systemic antibiotics are able to eliminate planktonic organisms released from the biofilm but are often ineffective in treating infections resulting from biofilm-embedded organisms. Biofilm resistance is usually multifactorial, which makes biofilm eradication difficult, and, thus, most biofilm-related infections require prompt removal of the device. Intervention strategies for biofilm-associated infections include (1) prevention of initial device contamination, (2) minimization of initial microbial cell attachment, (3) use of agents such as high-dose antibiotics or antibiofilm agent in a catheter lock solution to penetrate the biofilm matrix and kill the embedded organisms, and (4) removal of the infected device. Some antibacterials are better than others in treating biofilm-associated bacteria, such as rifampin (in combination with other antibiotics), tigecycline, daptomycin, N-acetylysteine (in combination with tigecycline), and ethanol. PMID:19084156

Aslam, Saima

2008-12-01

267

Synthesis and evaluation of antibacterial activities of andrographolide analogues.  

PubMed

Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used for many years to treat a variety of diseases including bacterial and viral infections. Andro was recently reported to act by inhibiting the bacterial quorum sensing system. We have synthesized several Andro analogues and investigated their antibacterial activity and mechanism of action. The new compounds were found to be much more potent than the parent Andro in inhibiting bacterial growth and quorum sensing system. Compounds 5 and 7 significantly reduced virulence factor production. Compound 7 completely inhibited Pseudomonas aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic activity with conventional antibiotics. These findings suggest that compound 7 may be the basis for future drug development to combat the unmet needs of virulence factor production, biofilm formation and antibiotic resistance. PMID:19152987

Jiang, Xiaojian; Yu, Pei; Jiang, Jie; Zhang, Zaijun; Wang, Zhongli; Yang, Zhaoqi; Tian, Zhiming; Wright, Susan C; Larrick, James W; Wang, Yuqiang

2009-07-01

268

Relationship between clinical efficacy of treatment of pulmonary Mycobacterium avium complex disease and drug-sensitivity testing of Mycobacterium avium complex isolates  

Microsoft Academic Search

We prospectively investigated the relationship between the clinical efficacy of treatment of pulmonary Mycobacterium avium complex (MAC) disease and drug-sensitivity testing of MAC isolates for antituberculous drugs, new quinolone antibiotics,\\u000a and clarithromycin (CAM). Fifty-two patients who satisfied the diagnostic criteria of the American Thoracic Society (ATS)\\u000a and who received treatment between April 1998 and December 2005, using combined therapy of

Yoshihiro Kobashi; Kouichiro Yoshida; Naoyuki Miyashita; Yoshihito Niki; Mikio Oka

2006-01-01

269

Spontaneous Conversion to Quinolone and Fluoroquinolone Resistance among Wild-Type Escherichia coli Isolates in Relation to Phylogenetic Background and Virulence Genotype  

PubMed Central

Human clinical isolates of Escherichia coli that are resistant to quinolone or fluoroquinolone agents typically exhibit fewer extraintestinal virulence factors (VFs) than susceptible isolates, along with a different phylogenetic background. To experimentally assess the basis for this as-yet-unexplained phenomenon, 40 E. coli strains (20 E. coli Reference collection members and 20 Israeli cystitis isolates) were subjected to serial selective passaging to obtain derivatives resistant to nalidixic acid (NA) and ciprofloxacin (C). PCR-based VF profiling and phylotyping were performed on the parents and their respective resistant derivatives. All 40 susceptible parent strains yielded NA- and C-resistant derivatives after a median of 6 (range, 4 to 12) serial selective passages on agar plates containing increasing concentrations of NA and C. The numbers of passages required for resistance did not differ by collection origin, phylogenetic group, basal VF profile, source (urine versus fecal), or host group (human versus animal). With the development of C resistance, only one VF was lost in a single strain. Resistant derivatives exhibited the same phylotype as their susceptible parents. These findings suggest that the sparse VF profiles and the low-virulence phylogenetic background of NA- and C-resistant E. coli clinical isolates probably are not attributable to the loss of VFs from intrinsically high-virulence strains during conversion to resistance or to enhanced emergence of drug resistance among intrinsically low-virulence strains. A more likely explanation is the importation of resistant strains from an as-yet-undefined low-virulence external selection reservoir. PMID:16251319

Johnson, James R.; Johnston, Brian; Kuskowski, Michael A.; Colodner, Raul; Raz, Raul

2005-01-01

270

Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations.  

PubMed Central

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in increased interest in the fluoroquinolones (FQs) as antituberculosis agents. To investigate the frequency and mechanisms of FQ resistance in M. tuberculosis, we cloned and sequenced the wild-type gyrA and gyrB genes, which encode the A and B subunits of the DNA gyrase, respectively; DNA gyrase is the main target of the FQs. On the basis of the sequence information, we performed DNA amplification for sequencing and single-strand conformation polymorphism analysis to examine the presumed quinolone resistance regions of gyrA and gyrB from reference strains (n = 4) and clinical isolates (n = 55). Mutations in codons of gyrA analogous to those described in other FQ-resistant bacteria were identified in all isolates (n = 14) for which the ciprofloxacin MIC was > 2 micrograms/ml. In addition, we selected ciprofloxacin-resistant mutants of Mycobacterium bovis BCG and M. tuberculosis Erdman and H37ra. Spontaneously resistant mutants developed at a frequency of 1 in 10(7) to 10(8) at ciprofloxacin concentrations of 2 micrograms/ml, but no primary resistant colonies were selected at higher ciprofloxacin concentrations. Replating of those first-step mutants selected for mutants with high levels of resistance which harbored gyrA mutations similar to those found among clinical FQ-resistant isolates. The gyrA and gyrB sequence information will facilitate analysis of the mechanisms of resistance to drugs which target the gyrase and the implementation of rapid strategies for the estimation of FQ susceptibility in clinical M. tuberculosis isolates. Images PMID:8031045

Takiff, H E; Salazar, L; Guerrero, C; Philipp, W; Huang, W M; Kreiswirth, B; Cole, S T; Jacobs, W R; Telenti, A

1994-01-01

271

Original article Does Bacillus larvae produce an antibacterial  

E-print Network

Original article Does Bacillus larvae produce an antibacterial substance in infected honey bee-negative bacteria including Pseudomo- nas aeruginosa. The activity of the antibacterial substance was unaffected of an antibacterial substance released into Bailey's liquid medium during sporulation of B larvae; however, the aque

Boyer, Edmond

272

Drug forecast - the peptide deformylase inhibitors as antibacterial agents  

PubMed Central

The relatively rapid development of microbial resistance after the entry of every new antimicrobial into the marketplace necessitates a constant supply of new agents to maintain effective pharmacotherapy. Despite extensive efforts to identify novel lead compounds from molecular targets, only the peptide deformylase inhibitors (PDIs) have shown any real promise, with some advancing to phase I human trials. Bacterial peptide deformylase, which catalyzes the removal of the N-formyl group from N-terminal methionine following translation, is essential for bacterial protein synthesis, growth, and survival. The majority of PDIs are pseudopeptide hydroxamic acids and two of these (IV BB-83698 and oral NVP LBM-415) entered phase I human trials. However, agents to the present have suffered from major potential liabilities. Their in vitro activity has been limited to gram-positive aerobes and some anaerobes and has been quite modest against the majority of such species (MIC90 values ranging from 1–8 mg/L). They have exerted bacteriostatic, not bacteriocidal, activity, thus reducing their potential usefulness in the management of serious infections in the immunocompromised. The relative ease with which microorganisms have been able to develop resistance and the multiple available mechanisms of resistance (mutations in fmt, defB, folD genes; AcrAB/TolC efflux pump; overexpression of peptide deformylase) are worrisome. These could portend a short timespan of efficacy after marketing. Despite these current liabilities, further pursuit of more potent and broader spectrum PDIs which are less susceptible to bacterial mechanisms of resistance is still warranted. PMID:18472972

Guay, David R P

2007-01-01

273

Targeting Antibacterial Agents by Using Drug-Carrying Filamentous Bacteriophages  

Microsoft Academic Search

Bacteriophages have been used for more than a century for (unconventional) therapy of bacterial infections, for half a century as tools in genetic research, for 2 decades as tools for discovery of specific target-binding proteins, and for nearly a decade as tools for vaccination or as gene delivery vehicles. Here we present a novel application of filamentous bacteriophages (phages) as

Iftach Yacoby; Marina Shamis; Hagit Bar; Doron Shabat; Itai Benhar

2006-01-01

274

Effects of AntiBacterial Agents, Sample Preparation and Contact Time on AntiBacterial Efficacy in MDPE Film  

Microsoft Academic Search

The anti-bacterial efficacy of medium-density polyethylene (MDPE) with various contents of different anti-bacterial agents was studied with respect to the effects of the anti-bacterial concentration, size and form of MDPE test-specimen, and the contact time. The three anti-bacterial agents used were carbendazim and zinc dimethyl dithiocarbamate (TROYSAN-S88), 2-hydroxypropyl3-piperazinyl-quinoline carboxylic acid methacrylate (HPQM), and silver substituted zeolite (ZEOMIC). The halo and

Pakawat Chammanee; Kwannate Sombatsompop; Apisit Kositchaiyong; Narongrit Sombatsompop

2009-01-01

275

Injectable bioadhesive hydrogels with innate antibacterial properties.  

PubMed

Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5?wt% oxidized dextran and 6.9?wt% polyethylenimine sets within seconds forming a mechanically rigid (~1,700?Pa) gel offering a maximum adhesive stress of ~2.8?kPa. A murine infection model showed that the adhesive is capable of killing Streptococcus pyogenes introduced subcutaneously at the bioadhesive's surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound-filling applications. PMID:24958189

Giano, Michael C; Ibrahim, Zuhaib; Medina, Scott H; Sarhane, Karim A; Christensen, Joani M; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P

2014-01-01

276

Antibacterial resistance leadership group: open for business.  

PubMed

Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance. PMID:24610430

Chambers, Henry F; Bartlett, John G; Bonomo, Robert A; Chiou, Christine; Cosgrove, Sara E; Cross, Heather R; Daum, Robert S; Downing, Michele; Evans, Scott R; Knisely, Jane; Kreiswirth, Barry N; Lautenbach, Ebbing; Mickley, Brenda S; Patel, Robin; Pettigrew, Melinda M; Rodvold, Keith A; Spellberg, Brad; Fowler, Vance G

2014-06-01

277

Antibacterial nanofiber materials activated by light.  

PubMed

Electrospun polymeric nanofiber materials doped with 5,10,15,20-tetraphenylporphyrin (TPP) photosensitizer were prepared from four different polymers and were characterized with microscopic methods, steady-state, and time-resolved fluorescence and absorption spectroscopy. The polymers used included polyurethane Larithane™ (PUR), polystyrene (PS), polycaprolactone (PCL), and polyamide 6 (PA6). The antibacterial activity of all nanofiber materials against E. coli was activated by visible light and it was dependent on oxygen permeability/diffusion coefficients and the diameter of the polymeric nanofibers. This activity is based on oxidation ability of singlet oxygen O?(¹?(g)) that is generated upon irradiation. All tested nanofiber materials exhibited prolonged antibacterial properties, even in the dark after long-duration irradiation. The post-irradiation effect was explained by the photogeneration of H?O?, which provided the material with long-lasting antibacterial properties. PMID:21972201

Jesenská, So?a; Plíštil, Lukáš; Kubát, Pavel; Lang, Kamil; Brožová, Libuše; Popelka, St?pán; Szatmáry, Lórant; Mosinger, Ji?í

2011-12-15

278

New Plasmid-Mediated Quinolone Resistance Gene, qnrC, Found in a Clinical Isolate of Proteus mirabilis?  

PubMed Central

Since the discovery of qnrA in 1998, two additional qnr genes, qnrB and qnrS, have been described. These three plasmid-mediated genes contribute to quinolone resistance in gram-negative pathogens worldwide. A clinical strain of Proteus mirabilis was isolated from an outpatient with a urinary tract infection and was susceptible to most antimicrobials but resistant to ampicillin, sulfamethoxazole, and trimethoprim. Plasmid pHS10, harbored by this strain, was transferred to azide-resistant Escherichia coli J53 by conjugation. A transconjugant with pHS10 had low-level quinolone resistance but was negative by PCR for the known qnr genes, aac(6?)-Ib-cr and qepA. The ciprofloxacin MIC for the clinical strain and a J53/pHS10 transconjugant was 0.25 ?g/ml, representing an increase of 32-fold relative to that for the recipient, J53. The plasmid was digested with HindIII, and a 4.4-kb DNA fragment containing the new gene was cloned into pUC18 and transformed into E. coli TOP10. Sequencing showed that the responsible 666-bp gene, designated qnrC, encoded a 221-amino-acid protein, QnrC, which shared 64%, 42%, 59%, and 43% amino acid identity with QnrA1, QnrB1, QnrS1, and QnrD, respectively. Upstream of qnrC there existed a new IS3 family insertion sequence, ISPmi1, which encoded a frameshifted transposase. qnrC could not be detected by PCR, however, in 2,020 strains of Enterobacteriaceae. A new quinolone resistance gene, qnrC, was thus characterized from plasmid pHS10 carried by a clinical isolate of P. mirabilis. PMID:19258263

Wang, Minghua; Guo, Qinglan; Xu, Xiaogang; Wang, Xiaoying; Ye, Xinyu; Wu, Shi; Hooper, David C.; Wang, Minggui

2009-01-01

279

New plasmid-mediated quinolone resistance gene, qnrC, found in a clinical isolate of Proteus mirabilis.  

PubMed

Since the discovery of qnrA in 1998, two additional qnr genes, qnrB and qnrS, have been described. These three plasmid-mediated genes contribute to quinolone resistance in gram-negative pathogens worldwide. A clinical strain of Proteus mirabilis was isolated from an outpatient with a urinary tract infection and was susceptible to most antimicrobials but resistant to ampicillin, sulfamethoxazole, and trimethoprim. Plasmid pHS10, harbored by this strain, was transferred to azide-resistant Escherichia coli J53 by conjugation. A transconjugant with pHS10 had low-level quinolone resistance but was negative by PCR for the known qnr genes, aac(6')-Ib-cr and qepA. The ciprofloxacin MIC for the clinical strain and a J53/pHS10 transconjugant was 0.25 microg/ml, representing an increase of 32-fold relative to that for the recipient, J53. The plasmid was digested with HindIII, and a 4.4-kb DNA fragment containing the new gene was cloned into pUC18 and transformed into E. coli TOP10. Sequencing showed that the responsible 666-bp gene, designated qnrC, encoded a 221-amino-acid protein, QnrC, which shared 64%, 42%, 59%, and 43% amino acid identity with QnrA1, QnrB1, QnrS1, and QnrD, respectively. Upstream of qnrC there existed a new IS3 family insertion sequence, ISPmi1, which encoded a frameshifted transposase. qnrC could not be detected by PCR, however, in 2,020 strains of Enterobacteriaceae. A new quinolone resistance gene, qnrC, was thus characterized from plasmid pHS10 carried by a clinical isolate of P. mirabilis. PMID:19258263

Wang, Minghua; Guo, Qinglan; Xu, Xiaogang; Wang, Xiaoying; Ye, Xinyu; Wu, Shi; Hooper, David C; Wang, Minggui

2009-05-01

280

Actinopyga lecanora Hydrolysates as Natural Antibacterial Agents  

PubMed Central

Actinopyga lecanora, a type of sea cucumber commonly known as stone fish with relatively high protein content, was explored as raw material for bioactive peptides production. Six proteolytic enzymes, namely alcalase, papain, pepsin, trypsin, bromelain and flavourzyme were used to hydrolyze A. lecanora at different times and their respective degrees of hydrolysis (DH) were calculated. Subsequently, antibacterial activity of the A. lecanora hydrolysates, against some common pathogenic Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas sp.) were evaluated. Papain hydrolysis showed the highest DH value (89.44%), followed by alcalase hydrolysis (83.35%). Bromelain hydrolysate after one and seven hours of hydrolysis exhibited the highest antibacterial activities against Pseudomonas sp., P. aeruginosa and E. coli at 51.85%, 30.07% and 30.45%, respectively compared to the other hydrolysates. Protein hydrolysate generated by papain after 8 h hydrolysis showed maximum antibacterial activity against S. aureus at 20.19%. The potent hydrolysates were further fractionated using RP-HPLC and antibacterial activity of the collected fractions from each hydrolysate were evaluated, wherein among them only three fractions from the bromelain hydrolysates exhibited inhibitory activities against Pseudomonas sp., P. aeruginosa and E. coli at 24%, 25.5% and 27.1%, respectively and one fraction of papain hydrolysate showed antibacterial activity of 33.1% against S. aureus. The evaluation of the relationship between DH and antibacterial activities of papain and bromelain hydrolysates revealed a meaningful correlation of four and six order functions. PMID:23222684

Ghanbari, Raheleh; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

2012-01-01

281

Secretion of Pseudomonas aeruginosa Type III Cytotoxins is Dependent on Pseudomonas Quinolone Signal Concentration  

PubMed Central

Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two-component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent posttranslational control, specifically governing type III cytotoxin secretion, exists in this species. PMID:20570614

Singh, G.; Wu, B.; Baek, M.S.; Camargo, A.; Nguyen, A.; Slusher, N.A.; Srinivasan, R.; Wiener-Kronish, J.P.; Lynch, S.V.

2010-01-01

282

Natural Products and Drug Discovery  

Microsoft Academic Search

For more than 50 yr, natural products have served us well in combating infectious bacteria and fungi. During the 20th century,\\u000a microbial and plant secondary metabolites helped to double our life span, reduced pain and suffering, and revolutionized medicine.\\u000a The increased development of resistance to older antibacterial, antifungal, and antitumor drugs has been challenged by (1) newly discovered antibiotics (e.g.,

Arnold L. Demain; Lixin Zhang

283

21 CFR 202.1 - Prescription-drug advertisements.  

...the drug or ingredient is a common substance, the limitations of which are readily...contains a broad claim that a drug is an antibacterial agent, the advertisement shall name...201.100 or 201.105. (4) Substance of information to be included in...

2014-04-01

284

21 CFR 202.1 - Prescription-drug advertisements.  

Code of Federal Regulations, 2013 CFR

...the drug or ingredient is a common substance, the limitations of which are readily...contains a broad claim that a drug is an antibacterial agent, the advertisement shall name...201.100 or 201.105. (4) Substance of information to be included in...

2013-04-01

285

Therapeutic approach to bronchiolitis: why pediatricians continue to overprescribe drugs?  

Microsoft Academic Search

BACKGROUND: Bronchiolitis guidelines suggest that neither bronchodilators nor corticosteroids, antiviral and antibacterial agents should be routinely used. Although recommendations, many clinicians persistently prescribe drugs for bronchiolitis. AIM OF THE STUDY: To unravel main reasons of pediatricians in prescribing drugs to infants with bronchiolitis, and to possibly correlate therapeutic choices to the severity of clinical presentation. Also possible influence of socially

Daniele De Brasi; Fortunato Pannuti; Fabio Antonelli; Federica de Seta; Paolo Siani; Luciano de Seta

2010-01-01

286

Comparative study of four fluorinated quinolones in susceptibility factors on microorganisms  

E-print Network

are veterinary products used to treat dermal, respiratory and urinary infections in small animals. Ciprofioxacin, however, is a human drug used for similar infections. The human drug, ciprofloxacin, is often cited as effective against selected microorganisms...

Patel, Ketul R

2013-02-22

287

Synthesis, spectral features and biological activity of some novel hetarylazo dyes derived from 8-chloro-4-hydroxyl-2-quinolone.  

PubMed

In this study, 8-chloro-4-hydroxyl-2-quinolone was synthesized from cyclocondensation of corresponding dianilide and subsequently used as a potent coupling component with some diazotized heterocyclic amines. These compounds were characterized by UV-vis, FT-IR, (1)H NMR spectroscopic techniques and elemental analysis. Absorption spectra of these dyes were measured in six polar solvents and discussed with respect to the nature of solvents and substituted groups. The effects of acid, base, temperature and concentration on the visible absorption spectra of the dyes were reported. In addition, the antimicrobial activity of the dyes was explored in detail. PMID:24140457

Yahyazadeh, Asieh; Yousefi, Hessamoddin

2014-01-01

288

Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3? (GSK-3?) inhibitors for type 2 diabetics.  

PubMed

The design, synthesis, and evaluation of 6-6-7 tricyclic quinolones containing the strained spirocycle moiety aiming at the GSK-3? inhibitor were described. Among the synthesized compounds, 44, having a cyclobutane ring on a spirocycle, showed excellent GSK-3? inhibitory activity in both cell-free and cell-based assays (IC(50) = 36nM, EC(50) = 3.2?M, respectively). Additionally, 44 decreased the plasma glucose concentration dose-dependently after an oral glucose tolerance test in mice. PMID:22261023

Seto, Shigeki; Yumoto, Kazuhiko; Okada, Kyoko; Asahina, Yoshikazu; Iwane, Aya; Iwago, Maki; Terasawa, Reiko; Shreder, Kevin R; Murakami, Koji; Kohno, Yasushi

2012-02-01

289

Antibacterial activity of gemini quaternary ammonium salts.  

PubMed

A series of gemini quaternary ammonium salts (chlorides and bromides), with various hydrocarbon chain and spacer lengths, were tested. These compounds exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria and were not mutagenic. The strongest antibacterial effect was observed for TMPG-10 Cl (against Pseudomonas aeruginosa ATCC 27853) and TMPG-12 Br (against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229 and clinical ESBL(+) isolate 434) surfactants. These compounds inhibited the adhesion of Staphylococcus epidermidis ATCC 35984 to a polystyrene surface and eradicated biofilm formed by P. aeruginosa PAO1. The activity of studied compounds was dependent on hydrocarbon chain length. PMID:24236547

Ob??k, Ewa; Piecuch, Agata; Guz-Regner, Katarzyna; Dworniczek, Ewa

2014-01-01

290

Antiviral and antibacterial polyurethanes of various modalities.  

PubMed

We have prepared and characterized a new polyurethane-based antimicrobial material, N,N-dodecyl,methyl-polyurethane (Quat-12-PU). It exhibits strong antiviral and antibacterial activities when coated (as an organic solution or an aqueous nanosuspension) onto surfaces and antibacterial activity when electrospun into nanofibers. Quat-12-PU surfaces are able to kill airborne Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria, as well as inactivate the enveloped influenza virus (but not the non-enveloped poliovirus). PMID:23306899

Park, Daewon; Larson, Alyssa M; Klibanov, Alexander M; Wang, Yadong

2013-02-01

291

Antibacterial activities of nemonoxacin against clinical isolates of Staphylococcus aureus: an in vitro comparison with three fluoroquinolones.  

PubMed

In comparison with ciprofloxacin, levofloxacin and moxifloxacin, antimicrobial activity of nemonoxacin against ciprofloxacin-susceptible/-resistant methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) was determined with the availability to select resistant mutants evaluated. Minimum inhibitory concentrations and mutant prevention concentrations of quinolones were determined by agar dilution method, that concentrated bacterial cells were spread onto Mueller-Hinton agar plates containing antibacterials at different concentrations. Selection index (SI) was calculated. Minimum inhibitory concentration and mutant prevention concentration of nemonoxacin were 0.063 and 0.25 ?g/mL for ciprofloxacin-susceptible MSSA and those were 0.5 and 4.0 ?g/mL for ciprofloxacin-resistant MSSA, lower than observations of three fluoroquinolones distinctly. SI of nemonoxacin and moxifloxacin were similar, with narrower mutant selective window than levofloxacin and ciprofloxacin. Minimum inhibitory concentration and mutant prevention concentration of nemonoxacin were 0.25 and 2.0 ?g/mL for ciprofloxacin-susceptible MRSA, which were 0.5 and 16.0 ?g/mL for ciprofloxacin-resistant MRSA. Values were lower than those determined from fluoroquinolones. Nemonoxacin presents good antimicrobial activity against clinical isolates of S. aureus, especially for ciprofloxacin-resistant strains. But stepwise mutant accumulation of ciprofloxacin-resistant MRSA can be hardly inhibited by nemonoxacin with pharmacokinetic parameters considered. PMID:25129332

Li, Zhaoxia; Liu, Youning; Wang, Rui; Li, Aimin

2014-11-01

292

Improved antibacterial activity and biocompatibility on vancomycin-loaded TiO2 nanotubes: in vivo and in vitro studies  

PubMed Central

The goal for current orthopedic implant research is to design implants that have not only good biocompatibility but also antibacterial properties. TiO2 nanotubes (NTs) were fabricated on the titanium surface through electrochemical anodization, which added new properties, such as enhanced biocompatibility and potential utility as drug nanoreservoirs. The aim of the present study was to investigate the antibacterial properties and biocompatibility of NTs loaded with vancomycin (NT-V), both in vitro and in vivo. Staphylococcus aureus was used to study the antibacterial properties of the NT-V. There were three study groups: the commercially pure titanium (Cp-Ti) group, the NT group (nonloaded vancomycin), and the NT-V group. We compared NT-V biocompatibility and antibacterial efficacy with those of the NT and Cp-Ti groups. Compared with Cp-Ti, NT-V showed good antibacterial effect both in vitro and in vivo. Although the NTs reduced the surface bacterial adhesion in vitro, implant infection still developed in in vivo studies. Furthermore, the results also revealed that both NTs and NT-V showed good biocompatibility. Therefore, the NTs loaded with antibiotic might be potentially used for future orthopedic implants. PMID:24403827

Zhang, Hangzhou; Sun, Yu; Tian, Ang; Xue, Xiang Xin; Wang, Lin; Alquhali, Ali; Bai, Xizhuang

2013-01-01

293

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?  

PubMed Central

Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general. PMID:11023961

Labro, Marie-Therese

2000-01-01

294

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.  

PubMed

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K(i) ranging from 4 to 250 ?M (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification. PMID:22933186

Ballester, Pedro J; Mangold, Martina; Howard, Nigel I; Robinson, Richard L Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B O

2012-12-01

295

Natural products as antibacterial agents  

Microsoft Academic Search

For thousands of years medicinal plants have played a significant role in the treatment of a wide range of medical conditions, including infectious diseases. Some naturally occurring chemical compounds serve as models for a large percentage clinically proven drugs, and many are now being re-assessed as antimicrobial agents. The primary reason for this renaissance is the fact that infectious disease

Gail B. Mahady; Yue Huang; Brian J. Doyle; Tracie Locklear

2008-01-01

296

Drug-resistant Neisseria gonorrhoeae in Michigan  

PubMed Central

The increasing prevalence of quinolone-resistant Neisseria gonorrhoeae (QRNG) in the United States is a cause for concern. Detecting resistance is complicated by the widespread use of molecular tests that do not provide isolates for susceptibility testing. The Michigan Department of Community Health developed a sentinel surveillance program to detect antimicrobial drug resistance in N. gonorrhoeae. Sentinel surveillance from 11 laboratories submitted 1,122 isolates for antimicrobial drug susceptibility testing and detected 2 clusters of QRNG from January 2003 to September 2004. These clusters were epidemiologically distinct: one involved young, heterosexual youth, and the other involved older men who have sex with men. This finding led to changes in local treatment recommendations that limited spread of resistant strains. Development of the sentinel program, collection of data, and epidemiologic analysis of the clusters are discussed. PMID:16022773

Boehme, Martha S.; Rudrik, James T.; Ganoczy, Dara; Crandell-Alden, Erin; Schneider, William A.; Somsel, Patricia A.

2005-01-01

297

The diversity of antibacterial compounds of Terminalia species (Combretaceae).  

PubMed

The antibacterial activity of acetone, hexane, dichloromethane leaf extract of five Terminalia species (Terminalia alata Heyne ex Roth., Terminalia arjuna (Roxb.) Wt. and Am., Terminalia bellerica (Gaertn.) Roxb., Terminalia catappa L. and Terminalia chebula Retz.) were tested by Agar-well-diffusion method against human pathogens E. coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and Staphylococcus epidermidis. The Rf values and relative activities of separated compounds were tested. Hexane and dichloromethane extracts have shown more antibacterial components than the acetone extract indicating the non-polar character of the antibacterial compounds. The non-polar character of the antibacterial compounds was confirmed from the Rf values. It indicated that the antibacterial activity was not due to tannins. Terminalia catappa found to possess the compounds which are more antibacterial. Terminalia arjuna and T. catappa plants were found most promising for isolating antibacterial compounds. PMID:20180323

Shinde, S L; Junne, S B; Wadje, S S; Baig, M M V

2009-11-15

298

Lead structures for new antibacterials: stereocontrolled synthesis of a bioactive muraymycin analogue.  

PubMed

Naturally occurring muraymycin nucleoside antibiotics represent a promising class of novel antibacterial agents. The structural complexity suggests the investigation of simplified analogues as potential lead structures, which can then be further optimized towards highly potent antimicrobials. Herein we report studies on muraymycin-derived potential lead structures lacking an aminoribose motif found in most naturally occurring muraymycins. We have identified a 5'-defunctionalized motif to be ideal in terms of stability and chemical accessibility and have synthesized a full-length muraymycin analogue based on this structure using a novel fully stereocontrolled route. The obtained 5'-deoxy analogue of the natural product muraymycin C4 showed good inhibitory properties towards the bacterial target protein MraY, sufficient pharmacokinetic stability and no cytotoxicity against human cells, thus making it a promising lead for antibacterial drug development. PMID:25318977

Spork, Anatol P; Büschleb, Martin; Ries, Oliver; Wiegmann, Daniel; Boettcher, Stefan; Mihalyi, Agnes; Bugg, Timothy D H; Ducho, Christian

2014-11-17

299

Antibacterial Activity of Honey on Cariogenic Bacteria  

PubMed Central

Objective: Honey has antibacterial activity. The aim of this study was to evaluate the antibacterial activity of honey on Streptococcus mutans and Lactobacillus. Materials and Methods: In this in vitro study, solutions containing 0%, 5%, 10%, 20%, 50% and 100%(w/v) of natural Hamadan honey were prepared. Each blood (nutrient) agar plate was then filled with dilutions of the honey. The strains of bacteria were inoculated in blood agar for 24 hours at 37°C and were adjusted according to the McFarland scale (10×10 cfumcl?1). All assays were repeated 10 times for each of the honey concentrations. Data were analyzed by non parametric Chi-Square test. Statistical significance was set at ?=0.05. Results: Significant antibacterial activity was detected for honey on Streptococcus mutans in concentrations more than 20% and on Lactobacillus in 100% concentration (P<0.05). Conclusion: It seems that antibacterial activity of honey could be used for prevention and reduction of dental caries. PMID:23724198

Ahmadi - Motamayel, Fatemeh; Hendi, Seyedeh Sare; Alikhani, Mohammad Yusof; Khamverdi, Zahra

2013-01-01

300

Antibacterial properties of propolis (bee glue).  

PubMed Central

Propolis (bee glue) was found to have antibacterial activity against a range of commonly encountered cocci and Gram-positive rods, including the human tubercle bacillus, but only limited activity against Gram-negative bacilli. These findings confirm previous reports of antimicrobial properties of this material, possibly attributable to its high flavonoid content. PMID:2182860

Grange, J M; Davey, R W

1990-01-01

301

Zulu medicinal plants with antibacterial activity  

Microsoft Academic Search

Aqueous, methanolic and ethyl acetate extracts of 14 plants used in traditional Zulu medicine for treatment of ailments of an infectious nature were screened for antibacterial activity. Most of the activity detected was against Gram-positive bacteria. Tuber bark extracts of Dioscorea sylvatica had activity against Gram-negative Escherichia coli and extracts of Dioscorea dregeana, Cheilanthes viridis and Vernonia colorata were active

Jonathan E. Kelmanson; Anna K. Jäger; Johannes van Staden

2000-01-01

302

[Determination of 16 quinolone residues in animal tissues using high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry].  

PubMed

A confirmative method was developed with high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-MS/MS) to simultaneously detect 16 quinolone residues in animal tissues, which included nalidixinic acid, oxolinic acid, flumequine, norfloxacin, enoxacin, ciprofloxacin, lomefloxacin, danofloxacin, enrofloxacin, ofloxacin, sarafloxacin, difloxacin, marbofloxacin, pefloxacin, sparfloxacin and orbifloxacin. In the method, the 16 residues were extracted with acidified acetonitrile, cleaned-up with hexane, and concentrated with a rotary evaporator. Then the reconstituted sample solution was analyzed using HPLC-MS/MS in positive mode, with a Inertsil C8-3 column as the analytical column. The method was validated at 10, 50 and 100 microg/kg. The validation results were as follows: the linear ranges were from 10 to 100 microg/kg; the overall recoveries were from 62.4% to 102% with the relative standard deviations of 1.4%-11.9%. The method is simple, rapid, and accurate, and its performance could meet the requirements of the domestic and international legislation. The method is applicable to simultaneously confirm multi-residues of quinolones in animal tissues such as chicken muscle, chicken liver and fish muscle. PMID:17970104

Yue, Zhenfeng; Lin, Xiuyun; Tang, Shaobing; Chen, Xiaoxia; Ji, Caini; Hua, Honghui; Liu, Yu

2007-07-01

303

Trace analysis of quinolone and fluoroquinolone antibiotics from wastewaters by liquid chromatography-electrospray tandem mass spectrometry.  

PubMed

A sensitive liquid chromatography-electrospray tandem mass spectrometry method, combined with solid-phase extraction and a weak cation exchange cartridge cleanup, was established for twenty quinolone and fluoroquinolone antibiotics (pipemidic acid, flerofloxacin, ofloxacin, pefloxacin, enoxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, lomefloxacin, difloxacin, sarafloxacin, gatifloxacin, sparfloxacin, moxifloxacin, cinoxacin, oxolinic acid, nalidixic acid, flumequine, and piromidic acid) in influent, effluent, and river waters. For the various water matrices considered, the overall recoveries were from 64% to 127% except for piromidic acid (27-33%), and no obvious matrix effect was observed. The method detection limits for the twenty target antibiotics in the influent, effluent, and surface water samples were 1.6-50 ng/L, 0.6-50 ng/L, and 0.8-50 ng/L, respectively. This method was applied to analyze residual quinolone and fluoroquinolone antibiotics in wastewater and surface water samples from Beijing, China. Eight antibiotics (12 (pipemidic acid)-1208 ng/L (ofloxacin)) were detected in wastewater, and seven (1.3 (lomefloxacin)-535 ng/L (ofloxacin)) were detected in surface water samples. Gatifloxacin, a 4th generation fluoroquinolone antibiotic, was detected for the first time in influent (111 ng/L), effluent (56 ng/L), and river water (16-42 ng/L). PMID:19007934

Xiao, Yang; Chang, Hong; Jia, Ai; Hu, Jianying

2008-12-19

304

Activity of Bay y3118 against quinolone-susceptible and -resistant gram-negative and gram-positive bacteria.  

PubMed Central

The activity of Bay y3118 against laboratory strains of bacteria, including those with mutations in gyrA, with decreased expression of outer membrane proteins, and/or that are multiply resistant, and 121 selected clinical isolates, including highly fluoroquinolone-resistant bacteria from Spain and Argentina, was determined. Bay y3118 was extremely active (MICs, < or = 1 microgram/ml) against all bacteria, including quinolone-resistant laboratory strains. However, Bay y3118 was less active against 46 of 121 quinolone-resistant clinical isolates, such that > or = 16 micrograms of Bay y3118 per ml was required to inhibit 3 isolates. The concentration of Bay y3118 required to inhibit DNA synthesis by 50% correlated well with the MIC. Bay y3118 had accumulation kinetics similar to those of previously studied fluoroquinolones, e.g., ciprofloxacin, and there was a 50% decrease in the steady-state concentration in those members of the family Enterobacteriaceae that lacked porin proteins. Magnesium chloride at 20 mM apparently abolished the accumulation of Bay y3118 into Escherichia coli and reduced the level of accumulation into other gram-negative bacteria and Staphylococcus aureus. Carbonyl cyanide m-chlorophenylhydrazone at 100 microM enhanced the accumulation of Bay y3118 into E. coli, but it had a minimal effect on accumulation into S. aureus. PMID:8203834

Piddock, L J; Marshall, A J; Jin, Y F

1994-01-01

305

Pseudomonas aeruginosa Alkyl Quinolones Repress Hypoxia-Inducible Factor 1 (HIF-1) Signaling through HIF-1? Degradation  

PubMed Central

The transcription factor hypoxia-inducible factor 1 (HIF-1) has recently emerged to be a crucial regulator of the immune response following pathogen perception, including the response to the important human pathogen Pseudomonas aeruginosa. However, as mechanisms involved in HIF-1 activation by bacterial pathogens are not fully characterized, understanding how bacteria and bacterial compounds impact on HIF-1? stabilization remains a major challenge. In this context, we have focused on the effect of secreted factors of P. aeruginosa on HIF-1 regulation. Surprisingly, we found that P. aeruginosa cell-free supernatant significantly repressed HIF-1? protein levels. Further characterization revealed that HIF-1? downregulation was dependent on a subset of key secreted factors involved in P. aeruginosa pathogenesis, the 2-alkyl-4-quinolone (AQ) quorum sensing (QS) signaling molecules, and in particular the pseudomonas quinolone signal (PQS). Under hypoxic conditions, the AQ-dependent downregulation of HIF-1? was linked to the suppressed induction of the important HIF-1 target gene hexokinase II. Furthermore, we demonstrated that AQ molecules directly target HIF-1? protein degradation through the 26S-proteasome proteolytic pathway but independently of the prolyl hydroxylase domain (PHD). In conclusion, this is the first report showing that bacterial molecules can repress HIF-1? protein levels. Manipulation of HIF-1 signaling by P. aeruginosa AQs could have major consequences for the host response to infection and may facilitate the infective properties of this pathogen. PMID:22949552

Legendre, Claire; Reen, F. Jerry; Mooij, Marlies J.; McGlacken, Gerard P.; Adams, Claire

2012-01-01

306

Synthesis of chromone, quinolone, and benzoxazinone sulfonamide nucleosides as conformationally constrained inhibitors of adenylating enzymes required for siderophore biosynthesis.  

PubMed

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 ?-ketosulfonamide intermediates. The synthesis of the chromone- and quinolone-3-sulfonamide intermediates features formylation of a ?-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 ?-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. PMID:23805993

Engelhart, Curtis A; Aldrich, Courtney C

2013-08-01

307

Antibacterial activity of selected Malaysian honey  

PubMed Central

Background Antibacterial activity of honey is mainly dependent on a combination of its peroxide activity and non-peroxide components. This study aims to investigate antibacterial activity of five varieties of Malaysian honey (three monofloral; acacia, gelam and pineapple, and two polyfloral; kelulut and tualang) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Methods Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed for semi-quantitative evaluation. Agar well diffusion assay was used to investigate peroxide and non-peroxide activities of honey. Results The results showed that gelam honey possessed lowest MIC value against S. aureus with 5% (w/v) MIC and MBC of 6.25% (w/v). Highest MIC values were shown by pineapple honey against E. coli and P. aeruginosa as well as acacia honey against E. coli with 25% (w/v) MIC and 50% (w/v) MBC values. Agar inhibition assay showed kelulut honey to possess highest total antibacterial activity against S. aureus with 26.49 equivalent phenol concentrations (EPC) and non-peroxide activity of 25.74 EPC. Lowest antibacterial activity was observed in acacia honey against E. coli with total activity of 7.85 EPC and non-peroxide activity of 7.59 EPC. There were no significant differences (p?>?0.05) between the total antibacterial activities and non-peroxide activities of Malaysian honey. The intraspecific correlation between MIC and EPC of E. coli (r?=?-0.8559) was high while that between MIC and EPC of P. aeruginosa was observed to be moderate (r?=?-0.6469). S. aureus recorded a smaller correlation towards the opposite direction (r?=?0.5045). In contrast, B.cereus showed a very low intraspecific correlation between MIC and EPC (r?=?-0.1482). Conclusions Malaysian honey, namely gelam, kelulut and tualang, have high antibacterial potency derived from total and non-peroxide activities, which implies that both peroxide and other constituents are mutually important as contributing factors to the antibacterial property of honey. PMID:23758747

2013-01-01

308

Design and synthesis of benzenesulfonanilides active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus  

Microsoft Academic Search

Vancomycin is mainly used as an antibacterial agent of last resort, but recently vancomycin-resistant bacterial strains have been emerging. Although new antimicrobials have been developed in order to overcome drug-resistant bacteria, many are structurally complex ?-lactams or quinolones. In this study, we aimed to create new anti-drug-resistance antibacterials which can be synthesized in a few steps from inexpensive starting materials.

Kensuke Namba; Xiaoxia Zheng; Kazunori Motoshima; Hidetomo Kobayashi; Akihiro Tai; Eizo Takahashi; Kenji Sasaki; Keinosuke Okamoto; Hiroki Kakuta

2008-01-01

309

6-Position optimization of tricyclic 4-quinolone-based inhibitors of glycogen synthase kinase-3?: discovery of nitrile derivatives with picomolar potency.  

PubMed

We previously disclosed tricylic, 6-carboxylic acid-bearing 4-quinolones as GSK-3? inhibitors. Herein we discuss the optimization of this series to yield a series of more potent 6-nitrile analogs with insignificant anti-microbial activity. Finally, kinase profiling indicated that members of this class were highly specific GSK-3 inhibitors. PMID:22202172

Li, Bei; Cociorva, Oana M; Nomanbhoy, Tyzoon; Li, Qiang; Nakamura, Kai; Nomura, Masahiro; Okada, Kyoko; Yumoto, Kazuhiro; Liyanage, Marek; Zhang, Melissa C; Aban, Arwin; Szardenings, Anna Katrin; Kozarich, John W; Kohno, Yasushi; Shreder, Kevin R

2012-01-15

310

Development of a copper-catalyzed amidation-base-promoted cyclization sequence for the synthesis of 2-aryl- and 2-vinyl1-4 quinolones  

E-print Network

A direct two-step method for the preparation of 2-aryl- and 2-vinyl-4-quinolones that utilizes a copper-catalyzed amidation of ortho-halophenones followed by a base-promoted Camps cyclization of the resulting N-(2-keto-aryl)amides ...

Jones, Carrie Preston

2007-01-01

311

Comparative single-dose pharmacokinetics of four quinolones, oxolinic acid, flumequine, sarafloxacin, and enrofloxacin, in Atlantic salmon (Salmo salar) held in seawater at 10 degrees C.  

PubMed Central

Quinolones are currently the most commonly used group of antimicrobial agents in Norwegian aquaculture. The aims of this study were to examine and compare the pharmacokinetic properties of the quinolones oxolinic acid, flumequine, sarafloxacin, and enrofloxacin after intravascular and oral administration to Atlantic salmon (Salmo salar) by using identical experimental designs. The study was performed in seawater at 10.2 +/- 0.2 degree C with Atlantic salmon weighing 240 +/- 50 g (mean +/- standard deviation). The bioavailability varied considerably among the four quinolones. Following oral administration of medicated feed, the bioavailabilities of oxolinic acid, flumequine, sarafloxacin, and enrofloxacin were 30.1, 44.7, 2.2, and 55.5%, respectively. Taking the different dosages (25 mg/kg of body weight for oxolinic acid and flumequine and 10 mg/kg for sarafloxacin and enrofloxacin) into account, enrofloxacin showed the highest maximum concentration in plasma, followed by flumequine, oxolinic acid, and sarafloxacin. Following intravenous administration, the volumes of distribution at steady state of oxolinic acid, flumequine, sarafloxacin, and enrofloxacin were 5.4, 3.5, 2.3, and 6.1 liters/kg, respectively. Hence, all the quinolones showed good tissue penetration in Atlantic salmon. The elimination half-life of three of the quinolones, oxolinic acid, flumequine, and sarafloxacin, was less than or equal to 24 h, with oxolinic acid showing the shortest (18.2 h). On the other hand, the elimination half-life of enrofloxacin was estimated to be 34.2 h, almost twice that of oxolinic acid. This study showed that flumequine and enrofloxacin had better pharmacokinetic properties, compared with those of oxolinic acid, in Atlantic salmon held in seawater. PMID:7625789

Martinsen, B; Horsberg, T E

1995-01-01

312

L,L-diaminopimelate aminotransferase (DapL): a putative target for the development of narrow-spectrum antibacterial compounds  

PubMed Central

Despite the urgent need for sustained development of novel antibacterial compounds to combat the drastic rise in antibiotic resistant and emerging bacterial infections, only a few clinically relevant antibacterial drugs have been recently developed. One of the bottlenecks impeding the development of novel antibacterial compounds is the identification of new enzymatic targets. The nutritionally essential amino acid anabolic pathways, for example lysine biosynthesis, provide an opportunity to explore the development of antibacterial compounds, since human genomes do not possess the genes necessary to synthesize these amino acids de novo. The diaminopimelate (DAP)/lysine (lys) anabolic pathways are attractive targets for antibacterial development since the penultimate lys precursor meso-DAP (m-DAP) is a cross-linking amino acid in the peptidoglycan (PG) cell wall of most Gram-negative bacteria and lys plays a similar role in the PG of most Gram-positive bacteria, in addition to its role as one of the 20 proteogenic amino acids. The L,L-diaminopimelate aminotransferase (DapL) pathway was recently identified as a novel variant of the DAP/lys anabolic pathways. The DapL pathway has been identified in the pathogenic bacteria belonging to the genus; Chlamydia, Leptospira, and Treponema. The dapL gene has been identified in the genomes of 381 or approximately 13% of the 2771 bacteria that have been sequenced, annotated and reposited in the NCBI database, as of May 23, 2014. The narrow distribution of the DapL pathway in the bacterial domain provides an opportunity for the development and or discovery of narrow spectrum antibacterial compounds. PMID:25309529

Triassi, Alexander J.; Wheatley, Matthew S.; Savka, Michael A.; Gan, Han Ming; Dobson, Renwick C. J.; Hudson, Andre O.

2014-01-01

313

Comprehensive screening and quantification of veterinary drugs in milk using UPLC–ToF-MS  

Microsoft Academic Search

Ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC–ToF-MS) has been used for screening\\u000a and quantification of more than 100 veterinary drugs in milk. The veterinary drugs represent different classes including benzimidazoles,\\u000a macrolides, penicillins, quinolones, sulphonamides, pyrimidines, tetracylines, nitroimidazoles, tranquillizers, ionophores,\\u000a amphenicols and non-steroidal anti-inflammatory agents (NSAIDs). After protein precipitation, centrifugation and solid-phase\\u000a extraction (SPE), the extracts were analysed by

A. A. M. Stolker; P. Rutgers; E. Oosterink; J. J. P. Lasaroms; R. J. B. Peters; J. A. van Rhijn; M. W. F. Nielen

2008-01-01

314

Cytocompatibility and Antibacterial Properties of Capping Materials  

PubMed Central

The aim of this study was to evaluate and compare the antimicrobial activity and cytocompatibility of six different pulp-capping materials: Dycal (Dentsply), Calcicur (Voco), Calcimol LC (Voco), TheraCal LC (Bisco), MTA Angelus (Angelus), and Biodentine (Septodont). To evaluate antimicrobial activity, materials were challenged in vitro with Streptococcus mutans, Streptococcus salivarius, and Streptococcus sanguis in the agar disc diffusion test. Cytocompatibility of the assayed materials towards rat MDPC-23 cells was evaluated at different times by both MTT and apoptosis assays. Results significantly differed among the different materials tested. Both bacterial growth inhibition halos and cytocompatibility performances were significantly different among materials with different composition. MTA-based products showed lower cytotoxicity and valuable antibacterial activity, different from calcium hydroxide-based materials, which exhibited not only higher antibacterial activity but also higher cytotoxicity. PMID:24959601

Arciola, Carla Renata; Monaco, Annachiara; Lombardini, Marco

2014-01-01

315

Penetratin and derivatives acting as antibacterial agents.  

PubMed

The synthesis, in vitro evaluation and conformational study of penetratin and structurally related derivatives acting as antibacterial agents are reported. Among the compounds evaluated here, two methionine sulphoxide derivatives (RQIKIWFQNRRM[O]KWKK-NH2 and RQIKIFFQNRRM[O]KFKK-NH2 ) exhibited the strongest antibacterial effect in this series. In order to better understand the antimicrobial activity obtained for these peptides, we performed an exhaustive conformational analysis using different approaches. Molecular dynamics simulations were performed using two different media (water and trifluoroethanol/water). The results of these theoretical calculations were corroborated using experimental CD measurements. The electronic study for these peptides was carried out using molecular electrostatic potentials obtained from RHF/6-31G(d) calculations. In addition, the non-apeptide RQIRRWWQR-NH2 showed strong inhibitory action against the Gram-negative and Gram-positive bacteria tested in this study. PMID:23581817

Garro, Adriana D; Olivella, Mónica S; Bombasaro, José A; Lima, Beatriz; Tapia, Alejandro; Feresin, Gabriela; Perczel, Andras; Somlai, Csaba; Penke, Botond; López Cascales, Javier; Rodríguez, Ana M; Enriz, Ricardo D

2013-08-01

316

Nature and Origin of the Antibacterial Substances in Honey  

Microsoft Academic Search

The nonperoxide antibacterial activity of honey and honey fractions was tested withStaphylococcus aureusandMicrococcus luteusbacterial species. Antibacterial activity correlated significantly with the honey acidity but did not correlate with honey pH. There were small differences between the antibacterial activities of different honey types: rhododendron, eucalyptus and orange honeys had a relatively low activity, whereas dandelion, honeydew and rape honeys had a

Stefan Bogdanov

1997-01-01

317

Downregulation of yidC in Escherichia coli by Antisense RNA Expression Results in Sensitization to Antibacterial Essential Oils Eugenol and Carvacrol  

PubMed Central

Background The rising drug resistance in pathogenic bacteria and inefficiency of current antibiotics to meet clinical requirements has augmented the need to establish new and innovative approaches for antibacterial drug discovery involving identification of novel antibacterial targets and inhibitors. Being obligatory for bacterial growth, essential gene products are considered vital as drug targets. The bacterial protein YidC is highly conserved among pathogens and is essential for membrane protein insertion due to which it holds immense potential as a promising target for antibacterial therapy. Methods/Principal Findings The aim of this study was to explore the feasibility and efficacy of expressed antisense-mediated gene silencing for specific downregulation of yidC in Escherichia coli. We induced RNA silencing of yidC which resulted in impaired growth of the host cells. This was followed by a search for antibacterial compounds sensitizing the YidC depleted cells as they may act as inhibitors of the essential protein or its products. The present findings affirm that reduction of YidC synthesis results in bacterial growth retardation, which warrants the use of this enzyme as a viable target in search of novel antibacterial agents. Moreover, yidC antisense expression in E. coli resulted in sensitization to antibacterial essential oils eugenol and carvacrol. Fractional Inhibitory Concentration Indices (FICIs) point towards high level of synergy between yidC silencing and eugenol/carvacrol treatment. Finally, as there are no known YidC inhibitors, the RNA silencing approach applied in this study put forward rapid means to screen novel potential YidC inhibitors. Conclusions/Significance The present results suggest that YidC is a promising candidate target for screening antibacterial agents. High level of synergy reported here between yidC silencing and eugenol/carvacrol treatment is indicative of a potential antibacterial therapy. This is the first report indicating that the essential gene yidC is a therapeutic target of the antibacterial essential oils eugenol and carvacrol in E. coli. PMID:23469191

Patil, Supriya Deepak; Sharma, Rajnikant; Srivastava, Santosh; Navani, Naveen Kumar; Pathania, Ranjana

2013-01-01

318

Antibacterial clerodane diterpenes from Goldenrod ( Solidago virgaurea)  

Microsoft Academic Search

Nine clerodane diterpenes, solidagoic acids C-I (1–7), cleroda-3,13(14)-dien-16,15:18,19-diolide (8) and cleroda-3,13(14)-dien-15,16:18,19-diolide (9) were isolated and characterised from the ethanol–ethyl acetate (1:1) extract of Solidago virgaurea. The structures were determined by NMR spectroscopic analysis. Several displayed moderate antibacterial activity against Staphylococcus aureus.

Courtney M. Starks; Russell B. Williams; Matt G. Goering; Mark O’Neil-Johnson; Vanessa L. Norman; Jin-Feng Hu; Eliane Garo; Grayson W. Hough; Stephanie M. Rice; Gary R. Eldridge

2010-01-01

319

Antibacterial activity of traditional Australian medicinal plants  

Microsoft Academic Search

Fifty-six ethanolic extracts of various parts of 39 plants used in traditional Australian Aboriginal medicine were investigated for their antibacterial activities against four Gram-positive (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus and Streptococcus pyogenes) and four Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium) bacterial species. In a plate-hole diffusion assay, 12 extracts inhibited the growth of one or

Enzo A Palombo; Susan J Semple

2001-01-01

320

Antibacterial activity of carbapenems against clinical isolates of respiratory bacterial pathogens in the northeastern region of Japan in 2007  

Microsoft Academic Search

As the increasing prevalence of resistant strains of respiratory bacterial pathogens has recently been reported, continuous\\u000a monitoring of the susceptibility of clinical isolates to antibacterial agents is important. We performed a surveillance study\\u000a focusing on the susceptibility of major respiratory bacterial pathogens in the northeastern region of Japan to carbapenems\\u000a and control drugs. A total of 168 bacterial strains isolated

Kazunori GomiShigeru; Shigeru Fujimura; Katsuhiro Fuse; Hidenari Takane; Yoshihisa Nakano; Yasuko Kariya; Toshiaki Kikuchi; Iku Kurokawa; Yutaka Tokue; Akira Watanabe

2011-01-01

321

Synthesis, Characterization, and Antibacterial Activity of Cross-Linked Chitosan-Glutaraldehyde  

PubMed Central

This present study deals with synthesis, characterization and antibacterial activity of cross-linked chitosan-glutaraldehyde. Results from this study indicated that cross-linked chitosan-glutaraldehyde markedly inhibited the growth of antibiotic-resistant Burkholderia cepacia complex regardless of bacterial species and incubation time while bacterial growth was unaffected by solid chitosan. Furthermore, high temperature treated cross-linked chitosan-glutaraldehyde showed strong antibacterial activity against the selected strain 0901 although the inhibitory effects varied with different temperatures. In addition, physical-chemical and structural characterization revealed that the cross-linking of chitosan with glutaraldehyde resulted in a rougher surface morphology, a characteristic Fourier transform infrared (FTIR) band at 1559 cm?1, a specific X-ray diffraction peak centered at 2? = 15°, a lower contents of carbon, hydrogen and nitrogen, and a higher stability of glucose units compared to chitosan based on scanning electron microscopic observation, FTIR spectra, X-ray diffraction pattern, as well as elemental and thermo gravimetric analysis. Overall, this study indicated that cross-linked chitosan-glutaraldehyde is promising to be developed as a new antibacterial drug. PMID:23670533

Li, Bin; Shan, Chang-Lin; Zhou, Qing; Fang, Yuan; Wang, Yang-Li; Xu, Fei; Han, Li-Rong; Ibrahim, Muhammad; Guo, Long-Biao; Xie, Guan-Lin; Sun, Guo-Chang

2013-01-01

322

(-)-Menthol based thixotropic hydrogel and its application as a universal antibacterial carrier.  

PubMed

A kind of novel hydrogelator based on (-)-menthol, a traditional cooling compound, tailed by an amino acid derivate through an alkyl chain, has been designed and synthesized. The hydrogelator containing an l-lysine can form a stable hydrogel with thixotropic character in a large pH range. An interesting feature is that the viscoelastic character of the hydrogel can be enhanced by mechanical force. The mechanism of the self-assembly process was investigated by means of IR, SEM, AFM and X-ray diffraction. The formation of three dimensional multiporous networks through acid base interactions and strong double hydrogen bonding between amino acids is proposed to be the driving force for the construction of the stable hydrogel. As a result, the hydrogelator can further gelate aqueous solutions of some confirmed antibacterial agents such as Zn(2+) and a series of water soluble organic antibiotic medicines like lincomycin, amoxicillin, etc., in such a unique way that the concentration of the antibacterial agents loaded into the hydrogel can be tuned to a large extent. The antimicrobial susceptibility of the hydrogels loaded with Zn(2+) or lincomycin is much more effective than that of the corresponding aqueous solution tested by the Oxford cup method. Furthermore, the hydrogelator is completely innoxious to living cells by measurement of MTT assay. Thus, the hydrogel can be developed as a universal carrier for antibacterial agents and may also be widely used in the fields of cell culture, tissue engineering, or drug delivery systems. PMID:24695880

Li, Yi; Zhou, Feng; Wen, Ying; Liu, Keyin; Chen, Liming; Mao, Yueyuan; Yang, Shiping; Yi, Tao

2014-05-01

323

Design, Synthesis, and Antibacterial Properties of Dual-Ligand Inhibitors of Acetyl-CoA Carboxylase.  

PubMed

There is an urgent demand for the development of new antibiotics due to the increase in drug-resistant pathogenic bacteria. A novel target is the multifunctional enzyme acetyl-CoA carboxylase (ACC), which catalyzes the first committed step in fatty acid synthesis and consists of two enzymes: biotin carboxylase and carboxyltransferase. Covalently attaching known inhibitors against these enzymes with saturated hydrocarbon linkers of different lengths generated dual-ligand inhibitors. Kinetic results revealed that the dual-ligands inhibited the ACC complex in the nanomolar range. Microbiology assays showed that the dual-ligand with a 15-carbon linker did not exhibit any antibacterial activity, while the dual-ligand with a 7-carbon linker displayed broad-spectrum antibacterial activity as well as a decreased susceptibility in the development of bacterial resistance. These results suggest that the properties of the linker are vital for antibacterial activity and show how inhibiting two different enzymes with the same compound increases the overall potency while also impeding the development of resistance. PMID:25280369

Silvers, Molly A; Robertson, Gregory T; Taylor, Carol M; Waldrop, Grover L

2014-11-13

324

The effect of PAMAM dendrimers on the antibacterial activity of antibiotics with different water solubility.  

PubMed

Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM dendrimers enhanced the pharmacological activity of antifungal drugs by increasing their solubility. Therefore, it appears interesting to investigate the effect of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 (G2) and generation 3 (G3) on the antibacterial activity of antibiotics with different water solubility. In this study it was shown that the aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM-NH2 and PAMAM-OH caused about 8- and 7- fold solubility increases, respectively). However, it was indicated that despite the increase in the solubility, there was only slight influence on the antibacterial activity of EM (2- and 4-fold decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH2 G2 or G3 for strains of Staphylococcus aureus were noted, respectively). It was also found that there was no influence of PAMAM on the antibacterial activity of hydrophilic TOB. PMID:23881050

Winnicka, Katarzyna; Wroblewska, Magdalena; Wieczorek, Piotr; Sacha, Pawel Tomasz; Tryniszewska, Elzbieta Anna

2013-01-01

325

Original article Antibacterial properties of propolis and products  

E-print Network

of these resins againstS aureus, B cereus and B subtilis was also determined. The results showed / quality control / antibacterial activity / Staphylococcus aureus / Bacillus cereus / Bacillus subtilis

Boyer, Edmond

326

Honey: its medicinal property and antibacterial activity  

PubMed Central

Indeed, medicinal importance of honey has been documented in the world's oldest medical literatures, and since the ancient times, it has been known to possess antimicrobial property as well as wound-healing activity. The healing property of honey is due to the fact that it offers antibacterial activity, maintains a moist wound condition, and its high viscosity helps to provide a protective barrier to prevent infection. Its immunomodulatory property is relevant to wound repair too. The antimicrobial activity in most honeys is due to the enzymatic production of hydrogen peroxide. However, another kind of honey, called non-peroxide honey (viz., manuka honey), displays significant antibacterial effects even when the hydrogen peroxide activity is blocked. Its mechanism may be related to the low pH level of honey and its high sugar content (high osmolarity) that is enough to hinder the growth of microbes. The medical grade honeys have potent in vitro bactericidal activity against antibiotic-resistant bacteria causing several life-threatening infections to humans. But, there is a large variation in the antimicrobial activity of some natural honeys, which is due to spatial and temporal variation in sources of nectar. Thus, identification and characterization of the active principle(s) may provide valuable information on the quality and possible therapeutic potential of honeys (against several health disorders of humans), and hence we discussed the medicinal property of honeys with emphasis on their antibacterial activities. PMID:23569748

Mandal, Manisha Deb; Mandal, Shyamapada

2011-01-01

327

What makes a natural clay antibacterial?  

PubMed

Natural clays have been used in ancient and modern medicine, but the mechanism(s) that make certain clays lethal against bacterial pathogens has not been identified. We have compared the depositional environments, mineralogies, and chemistries of clays that exhibit antibacterial effects on a broad spectrum of human pathogens including antibiotic resistant strains. Natural antibacterial clays contain nanoscale (<200 nm), illite-smectite and reduced iron phases. The role of clay minerals in the bactericidal process is to buffer the aqueous pH and oxidation state to conditions that promote Fe(2+) solubility. Chemical analyses of E. coli killed by aqueous leachates of an antibacterial clay show that intracellular concentrations of Fe and P are elevated relative to controls. Phosphorus uptake by the cells supports a regulatory role of polyphosphate or phospholipids in controlling Fe(2+). Fenton reaction products can degrade critical cell components, but we deduce that extracellular processes do not cause cell death. Rather, Fe(2+) overwhelms outer membrane regulatory proteins and is oxidized when it enters the cell, precipitating Fe(3+) and producing lethal hydroxyl radicals. PMID:21413758

Williams, Lynda B; Metge, David W; Eberl, Dennis D; Harvey, Ronald W; Turner, Amanda G; Prapaipong, Panjai; Poret-Peterson, Amisha T

2011-04-15

328

Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis.  

PubMed

The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of -1.20 +/- 0.32 Deltalog(10) CFU/ml. h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of -0.97 +/- 0.32 Deltalog(10) CFU/ml. h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC. PMID:15388454

Cottagnoud, Philippe; Pfister, Marc; Acosta, Fernando; Cottagnoud, Marianne; Flatz, Lukas; Kühn, Felix; Müller, Hans-Peter; Stucki, Armin

2004-10-01

329

Daptomycin Is Highly Efficacious against Penicillin-Resistant and Penicillin- and Quinolone-Resistant Pneumococci in Experimental Meningitis  

PubMed Central

The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of ?1.20 ± 0.32 ?log10 CFU/ml?·?h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of ?0.97 ± 0.32 ?log10 CFU/ml?·?h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC. PMID:15388454

Cottagnoud, Philippe; Pfister, Marc; Acosta, Fernando; Cottagnoud, Marianne; Flatz, Lukas; Kuhn, Felix; Muller, Hans-Peter; Stucki, Armin

2004-01-01

330

Hydrophilicity of quinolones is not an exclusive factor for decreased activity in efflux-mediated resistant mutants of Staphylococcus aureus.  

PubMed Central

The elevated expression of the norA gene is responsible for efflux-mediated resistance to quinolones in Staphylococcus aureus (E.Y.W. Ng, M. Trucksis, and D.C. Hooper, Antimicrob. Agents Chemother. 38:1345-1355, 1994). For S. aureus transformed with a plasmid containing the cloned norA gene, SA113(pTUS20) (H. Yoshida, M. Bogaki, S. Nakamura, K. Ubukata, and M. Konno, J. Bacteriol. 172:6942-6949, 1990), and an overexpressed mutant, SA-1199B (G.W. Kaatz, S.M. Seo, and C.A. Ruble, J. Infect. Dis. 163:1080-1086, 1991), the MICs of norfloxacin increased 16 and 64 times compared with its MICs for the recipient and wild-type strains, SA113 and SA-1199, respectively. MICs of CS-940, however, increased only two and eight times, even though these two fluoroquinolones are similarly hydrophilic (apparent logPs of approximately -1). No good correlation was found, among 15 developed and developing quinolones, between the increment ratio in MICs and hydrophobicity (r = 0.61). Analysis of the quantitative structure-activity relationship among 40 fluoroquinolones revealed that the MIC increment ratio was significantly correlated with the bulkiness of the C-7 substituent and bulkiness and hydrophobicity of the C-8 substituent of fluoroquinolones (r = 0.87) and not with its molecular hydrophobicity (r = 0.47). Cellular accumulation of norfloxacin in SA-1199B was significantly lower than that in SA-1199, and it was increased by addition of carbonyl cyanide m-chlorophenyl hydrazone. On the other hand, accumulations of CS-940 in these strains were nearly identical, and they were not affected by addition of the protonophore. PMID:8843290

Takenouchi, T; Tabata, F; Iwata, Y; Hanzawa, H; Sugawara, M; Ohya, S

1996-01-01

331

Characterization of carbapenemases, extended spectrum ?-lactamases, quinolone resistance and aminoglycoside resistance determinants in carbapenem-non-susceptible Escherichia coli from a teaching hospital in Chongqing, Southwest China.  

PubMed

Carbapenem-resistant Escherichiacoli isolates harboring carbapenemases or combining an extended-spectrum ?-lactamase (ESBL) enzyme with loss of porins present an increasingly urgent clinical danger. Combined resistance to aminoglycosides and fluoroquinolones in carbapeneme non-susceptible (CNS) isolates will inevitably create problems. In the current study, we characterized the carbapenemases and ESBLs, and the prevalence of quinolone resistance determinants and aminoglycoside resistance determinants in carbapenem-non-susceptible (CNS) E.coli isolates from a teaching hospital in Chongqing, Southwest China in 2012. Thirty non-duplicated CNS E.coli isolates were screened via antimicrobial susceptibility testing, and the drug resistance profiles of the 30 strains were analyzed. Carbapenemase genes blaKPC-2, ESBL genes including blaCTX-M-3, blaCTX-M-14, blaCTX-M-55 and blaTEM, ARD genes including aac(6')-Ib, armA and rmtB, and QRD genes including qnrA, qnrB, qnrC, qnrD, qnrS and aac(6')-Ib-cr were identified and clonal relatedness was investigated by pulsed-field gel electrophoresis. Of the 30 isolates, 2 (6.7%) harbored carbapenemase gene blaKPC-2; 29 (96.7%) carried ESBLs; 20 (66.7%) were QRD positive; and 11 (36.7%) were ARD positive. Between the two blaKPC-2 positive strains, one contained ESBL, QRD and ARD genes, while the other expressed ESBL genes but was negative for both QRD and ARD genes. Of the 29 ESBLs positive isolates, 2 (6.9%) were carbapenemase positive, 19 (65.5%) were QRD positive, and 11 (37.9%) were ARD positive. PFGE revealed genetic diversity among the 30 isolates, indicating that the high prevalence of CNS E. coli isolates was not caused by clonal dissemination. Production of ESBLs was associated with the carbapenem resistance and QRD genes were highly prevalent among the CNS E. coli isolates. Multiple resistant genes were co-expressed in the same isolates. This is the first report of a multidrug resistant carbapenem-non-susceptible E.coli co-harboring resistant determinants blaKPC-2, blaCTX-M-14, blaCTX-M-55, blaTEM, aac(6')-Ib-cr, qnrB, aac(6')-Ib and rmtB from Chongqing, mainland China. PMID:25107431

Zhang, Chuanming; Xu, Xiuyu; Pu, Shuli; Huang, Shifeng; Sun, Jide; Yang, Shuangshuang; Zhang, Liping

2014-10-01

332

Antibacterial Activity of New Dibenzoxepinone Oximes with Fluorine and Trifluoromethyl Group Substituents  

PubMed Central

In this paper we present the antimicrobial activity of some newly synthesized dibenz[b,e]oxepin derivatives bearing the oximino moiety, and fluorine (F) and trifluoromethyl (CF3) group substituents. The chemical structure and purity of the new compounds were assessed by using elemental analysis, NMR and FTIR spectroscopy. The new compounds were screened for their antibacterial activity towards Gram-positive and Gram-negative strains, by qualitative and quantitative assays. Our results demonstrated that the CF3 and F disubstituted compounds could be considered for the further development of novel antimicrobial drugs. PMID:22072897

Limban, Carmen; Chifiriuc, Mariana Carmen

2011-01-01

333

Antibacterial activity of traditional medicinal plants used by Haudenosaunee peoples of New York State  

PubMed Central

Background The evolution and spread of antibiotic resistance, as well as the evolution of new strains of disease causing agents, is of great concern to the global health community. Our ability to effectively treat disease is dependent on the development of new pharmaceuticals, and one potential source of novel drugs is traditional medicine. This study explores the antibacterial properties of plants used in Haudenosaunee traditional medicine. We tested the hypothesis that extracts from Haudenosaunee medicinal plants used to treat symptoms often caused by bacterial infection would show antibacterial properties in laboratory assays, and that these extracts would be more effective against moderately virulent bacteria than less virulent bacteria. Methods After identification and harvesting, a total of 57 different aqueous extractions were made from 15 plant species. Nine plant species were used in Haudenosaunee medicines and six plant species, of which three are native to the region and three are introduced, were not used in traditional medicine. Antibacterial activity against mostly avirulent (Escherichia coli, Streptococcus lactis) and moderately virulent (Salmonella typhimurium, Staphylococcus aureus) microbes was inferred through replicate disc diffusion assays; and observed and statistically predicted MIC values were determined through replicate serial dilution assays. Results Although there was not complete concordance between the traditional use of Haudenosaunee medicinal plants and antibacterial activity, our data support the hypothesis that the selection and use of these plants to treat disease was not random. In particular, four plant species exhibited antimicrobial properties as expected (Achillea millefolium, Ipomoea pandurata, Hieracium pilosella, and Solidago canadensis), with particularly strong effectiveness against S. typhimurium. In addition, extractions from two of the introduced species (Hesperis matronalis and Rosa multiflora) were effective against this pathogen. Conclusions Our data suggest that further screening of plants used in traditional Haudenosaunee medicine is warranted, and we put forward several species for further investigation of activity against S. typhimurium (A. millefolium, H. matronalis, I. pandurata, H. pilosella, R. multiflora, S. canadensis). PMID:21054887

2010-01-01

334

A simple method for primary screening of antibacterial peptides in plant seeds  

PubMed Central

Background and Objectives Regarding the importance of finding new antibacterial drugs, screening of plants as a promising resource are now conducted worldwide. In this study, we report the application of a simple previously described method for screening of different plant seeds in order to find the best resources of plant antimicrobial peptides. Materials and Methods Total water soluble protein of 10 different plant seeds were extracted and subjected to SDS-PAGE and subsequent agar-overlay bioassays. Standard strains of Staphylococcus aureus, Enterococcus faecium and Escherichia coli were included in the bioassays. This method also was used for total proteins precipitated by Ammonium sulphate which ensure the protein nature of the test substances. Molecular size and the amounts of effective peptides were estimated using Tricin-SDS-PAGE and densitometry. Results Two different plant seeds showed noticeable antibacterial activities against tested Gram positive bacteria and a moderate inhibitory effect on Gram negative ones. Based on the results of Tricin-SDS-PAGE analysis which were carried out in parallel to bioassays, it was concluded that effective antibacterial substances are peptides with molecular weight of slightly larger than 5 kDa. Conclusion On the basis of results of agar-overlay experiments and by screening of 10 different herbal seeds, we could introduce seeds of M. sativa L. and Onobrychis sativa Lam., as great sources of putative plant antibacterial peptides. The proposed screening method can be used for screening of large number of different plant seeds and even other parts of the plant body, regarding some necessary modification in total water soluble protein extraction steps. PMID:22347591

Aliahmadi, A; Roghanian, R; Emtiazi, G; Ghassempour, A

2011-01-01

335

Biotransformation of the antibiotic agent flumequine by ligninolytic fungi and residual antibacterial activity of the transformation mixtures.  

PubMed

Flumequine, a fluoroquinolone antibiotic, is applied preferably in veterinary medicine, for stock breeding and treatment of aquacultures. Formation of drug resistance is a matter of general concern when antibiotics such as flumquine occur in the environment. Thus, biodegradation of flumequine in solution was investigated using five different ligninolytic fungi. Irpex lacteus, Dichomitus squalens, and Trametes versicolor proved most efficient and transformed more than 90% of flumequine within 6 or even 3 days. Panus tigrinus and Pleurotus ostreatus required up to 14 days to remove >90% of flumequine. Analyses of the metabolites by liquid chromatography-mass spectrometry suggest different transformation pathways for the different fungal strains. Structure proposals were elaborated for 8 metabolites. 7-Hydroxy-flumequine and flumequine ethyl ester were identified as common metabolites produced by all ligninolytic fungi. The largest variety of metabolites was formed by D. squalens. Residual antibacterial activity of the metabolite mixtures was tested using gram-positive and gram-negative bacteria. While for the less efficient P. tigrinus and P. ostreatus cultures the antibacterial activities corresponded to the residual concentrations of flumequine, a remarkable antibacterial activity remained in the D. squalens cultures although flumequine was transformed to more than 90%. Obviously, antibacterially active transformation products were formed by this fungal strain. PMID:24261869

Cvan?arová, Monika; Moeder, Monika; Filipová, Alena; Reemtsma, Thorsten; Cajthaml, Tomáš

2013-12-17

336

Geographical epidemiology of antibacterials in the preschool age  

PubMed Central

Abstract Background Thematic maps allow a more rapid and immediate reading of the geographical differences in the distribution of data referred to a specific territory. The aim of this study was to show, for the first time, the application of some statistical and cartographic tools in the analysis of drug utilization in the pediatric population of an Italian region, and to assess the intra-regional difference in the antibiotic prescriptions. Methods To assess the type of geographic distribution of the prescriptions, the analyses were based on the standardized prevalence rate (z-score) calculated at the local health unit, health district, and municipality levels. Pearson’s coefficient of correlation was used to evaluate the correlation with hospitalization and the Moran’s I index was used to evaluate the existence of spatial autocorrelation. With the use of Getis-Ord’s G statistic, clusters of areas with high and low levels of prevalence were identified and mapped. The probability of receiving at least one prescription of antibacterials during the year for all the children included in the study was evaluated with a logistic regression model. Results With the use of the maps it was possible to see that the prescriptions were not correlated with the health status of the population, but with the tendency of the pediatrician to prescribe drugs. This was also confirmed by the logistic regression model constructed to estimate the probability of receiving at least one prescription of antibacterials considering, as independent variables: age, sex, prevalence of hospitalizations in the district of residence, prescriptive attitude of the pediatrician, sex of the pediatrician, pediatrician’s age group, and duration of the pediatrician’s contract with the local health unit (LHU). Conclusions The priority actions to rationalize the use of antibacterials in the preschool age should concentrate on the active participation of the pediatricians in permanent education activities. Moreover, the competent authorities should increasing their efforts to limit unnecessary prescriptions and increase appropriateness of prescribing. Riassunto Introduzione Le mappe tematiche consentono una più rapida ed immediata lettura delle differenze geografiche nella distribuzione di dati riferiti ad un territorio specifico. Lo scopo dello studio è mostrare, per la prima volta, l’applicazione di alcuni strumenti statistici e cartografici, nell’analisi dell’uso dei farmaci nella popolazione pediatrica di una regione italiana e valutare le differenze intra-regionali. Metodi Per valutare il tipo di distribuzione geografica delle prescrizioni, sono stati calcolati i tassi di prevalenza standardizzati (punteggi-z) a livello di ASL, Distretti Sanitari e Comuni. Per valutare la correlazione con le ospedalizzazioni è stato usato il coefficiente di correlazione di Pearson; per valutare l’esistenza di autocorrelazione spaziale è stato usato l’indice I di Moran. Tramite l’uso della statistica G di Getis-Ord sono stati identificati cluster di aree ad alto e basso livello di prevalenza. Infine con un modello di regressione logistica è stata stimata la probabilità di ricevere almeno una prescrizione nel corso dell’anno per tutti i pazienti inclusi nello studio. Risultati Con l’uso delle mappe è possibile vedere che le prescrizioni non sono correlate con lo stato di salute della popolazione, ma sono correlate con l’attitudine prescrittiva del pediatra. Questo è confermato anche dal modello di regressione logistica costruito per stimare la probabilità di ricevere almeno una prescrizione considerando come variabili indipendenti l’età, il sesso, la prevalenza di ricoveri nel distretto di residenza, l’attitudine prescrittiva del pediatra, la classe di età del pediatra e la durata della convenzione del pediatra con l’Azienda Sanitaria Locale (ASL). Conclusioni Gli interventi primari per razionalizzare lȁ

2012-01-01

337

Synthesis and antibacterial activity of nitroaryl thiadiazole-levofloxacin hybrids.  

PubMed

Novel levofloxacin-containing hybrids carrying a 5-(nitroaryl)-1,3,4-thiadiazol-2-yl group were synthesized and evaluated in vitro against Gram-positive and Gram-negative bacteria. Preliminary data indicated that levofloxacin-nitrofuran and levofloxacin-nitroimidazole hybrids have a potent activity against Gram-positive organisms with enhanced anti-staphylococcal activity compared with the parent quinolone (N-desmethyl levofloxacin). PMID:17036368

Foroumadi, Alireza; Mansouri, Shahla; Emami, Saeed; Mirzaei, Javad; Sorkhi, Maedeh; Saeid-Adeli, Nosratollah; Shafiee, Abbas

2006-11-01

338

Cytotoxicity and antibacterial activity of extractives from Wedelia calendulacea  

Microsoft Academic Search

The cytotoxicity and antibacterial activity of petroleum ether, chloroform and methanol extracts of Wedelia calendulacea were assayed by brine shrimp lethality bioassay and standardized disk diffusion method against 19 bacterial strains. Three diterpenes isolated from the plant were also evaluated for in vitro antibacterial activities. The LC50 for the crude extracts against the brine shrimp nauplii were found to be

A. K. M Mottakin; R Chowdhury; M. S Haider; K. M Rahman; C. M Hasan; M. A Rashid

2004-01-01

339

Confronting the challenges of discovery of novel antibacterial agents.  

PubMed

Bacterial resistance is inevitable and is a growing concern. It can be addressed only by discovery and development of new agents. However the discovery and development of new antibacterial agents are at an all time low. This article broadly examines the historical as well as current status of antibacterial discovery and provides some perspective as how to address some of the challenges. PMID:25017034

Singh, Sheo B

2014-08-15

340

An Antibacterial Substance from Arctium minus and Onopordon tauricum  

Microsoft Academic Search

EXTRACTS of Arctium minus Bernh. (a plant which was erroneously listed in a previous publication1 as Arctium lappa L.) were found by Osborn1 to contain an antibacterial principle. In May 1945 the substance responsible for the antibacterial action of the extracts was isolated from the radical leaves of Arctium minus Bernh. in a crystalline form. More recently, the same substance

E. P. Abraham; A. E. Joseph; D. M. Crowfoot; E. M. Osborn

1946-01-01

341

The origin of the antibacterial property of bamboo  

Microsoft Academic Search

Bamboo is an eco-friendly and multifunctional plant. Bamboo clothing has recently entered the textile market with a claim for its antimicrobial properties, but without scientific evidence. In this study, the antibacterial activity of plant extracts from Australian-grown bamboo (Phyllostachys pubescens) is investigated. Bamboo extracts were made using water, dimethyl sulphoxide (DMSO) and dioxane and their antibacterial properties were compared against

T. Afrin; T. Tsuzuki; R. K. Kanwar; X. Wang

2012-01-01

342

Biological Sciences INVITRO ANTIBACTERIAL ACTIVITY OF SARGASSUM WIGHTII  

E-print Network

The antibacterial activity of Sargassum weightti was screened against human bacterial pathogens like bacillus cereus, Klebsiella pneumonia, Streptococcus pyogenes, Vibrio cholerae, E. coli, Proteus vulgaris and Salmonella typhi. The maximum activity was recorded from the extract of Sargassum weightti against K. pnuemoniae and minimum activity against streptococcus pyogenes. KEY WORDS Antibacterial activity, Mandapam coast, human bacterial pathogens.

P. Vengadesan; S. Ahmed John

343

Screening of Yemeni medicinal plants for antibacterial and cytotoxic activities  

Microsoft Academic Search

Ethanolic extracts of 20 selected plant species used by Yemeni traditional healers to treat infectious diseases were screened for their antibacterial activity against both Gram-positive and Gram-negative bacteria, as well as for cytotoxic activity. Fourteen of the ethanolic extracts showed variable degrees of antibacterial activity. The active ethanolic extracts were partitioned between ethyl acetate and water for a first separation.

N. A. Awadh Ali; W.-D Jülich; C Kusnick; U Lindequist

2001-01-01

344

Screening of some Palestinian medicinal plants for antibacterial activity  

Microsoft Academic Search

Antibacterial activity of organic and aqueous extracts of 15 Palestinian medicinal plants were carried against eight different species of bacteria: Bacillus subtilis, two Escherichia coli species, Staphylococcus aureus (methicillin resistant), two S. aureus (methicillin sensitive) species, Pseudomonas aeruginosa, and Enterococcus fecalis. Of the 15 plants tested, eight showed antibacterial activity. Each plant species has unique against different bacteria. The most

T Essawi; M Srour

2000-01-01

345

Synergistic actions of antibacterial neutrophil defensins and cathelicidins  

Microsoft Academic Search

Objective: Activated neutrophils extracellularly release antibacterial defensins and cathelicidins from the granules. In this study, to elucidate the interactions between defensins and cathelicidins in the extracellular environment, we evaluated the individual and synergistic actions of defen- sins and cathelicidins in the presence of physiological con- centration of NaCl (150 mM). Materials and Methods: Antibacterial activities against Escherichia coli and Staphylococcus

I. Nagaoka; S. Hirota; S. Yomogida; A. Ohwada; M. Hirata

2000-01-01

346

Antibacterial property of DLC film coated on textile material  

Microsoft Academic Search

To evaluate the antibacterial property for diamond-like carbon films (DLC), DLC films were coated on textile material (cotton fibres) using a plasma-based ion implantation (PBII). Raman spectra show the DLC films were successfully coated on the cotton fibres. An antibacterial property of DLC film against two types of bacteria (Staphylococcus aureus, and Klebsiella pneumoniae) was investigated by the standard evaluation

N. Kitahara; T. Sato; H. Isogawa; Y. Ohgoe; S. Masuko; F. Shizuku; K. K. Hirakuri

2010-01-01

347

Screening seeds of Scottish plants for antibacterial activity  

Microsoft Academic Search

Based on ethnopharmacological and taxonomic information, seeds of 21 Scottish plant species from 14 different families were obtained from authentic seed suppliers. Their n-hexane, dichloromethane and methanol extracts were assessed for antibacterial activity against 11 pathogenic bacterial species. Methanol extracts of 11 plant species showed significant antibacterial activity. Malva moschata and Prunus padus were active against five bacterial species, Reseda

Yashodharan Kumarasamy; Philip John Cox; Marcel Jaspars; Lutfun Nahar; Satyajit Dey Sarker

2002-01-01

348

Exploring Anti-Bacterial Compounds against Intracellular Legionella  

PubMed Central

Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the ?-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

Harrison, Christopher F.; Kicka, Sebastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

2013-01-01

349

Environmentally friendly antibacterial cotton textiles finished with siloxane sulfopropylbetaine.  

PubMed

This paper reports a novel environmentally friendly antibacterial cotton textile finished with reactive siloxane sulfopropylbetaine(SSPB). The results show that SSPB can be covalently bound onto the cotton textile surface, imparting perdurable antibacterial activity. The textiles finished with SSPB have been investigated systematically from the mechanical properties, thermal stability, hydrophilic properties and antibacterial properties. It is found that the hydrophilicity and breaking strength are improved greatly after the cotton textiles are finished with SSPB. Additionally, the cotton textiles finished with SSPB exhibit good antibacterial activities against gram-positive bacteria Staphylococcus aureus (S.aureus, ATCC 6538), gram-negative bacteria Escherichia coli (E.coli, 8099) and fungi Candida albicans (C.albicans, ATCC 10231). Moreover, SSPB is nonleachable from the textiles, and it does not induce skin stimulation and is nontoxic to animals. Thus, SSPB is ideal candidate for environmentally friendly antibacterial textile applications. PMID:21417413

Chen, Shiguo; Chen, Shaojun; Jiang, Song; Xiong, Meiling; Luo, Junxuan; Tang, Jiaoning; Ge, Zaochuan

2011-04-01

350

In Vitro Antibacterial Activity of Essential Oils against Streptococcus pyogenes.  

PubMed

Streptococcus pyogenes plays an important role in the pathogenesis of tonsillitis. The present study was conducted to evaluate the in vitro antibacterial activities of 18 essential oils chemotypes from aromatic medicinal plants against S. pyogenes. Antibacterial activity of essential oils was investigated using disc diffusion method. Minimum Inhibitory Concentration of essential oils showing an important antibacterial activity was measured using broth dilution method. Out of 18 essential oils tested, 14 showed antibacterial activity against S. pyogenes. Among them Cinnamomum verum, Cymbopogon citratus, Thymus vulgaris CT thymol, Origanum compactum, and Satureja montana essential oils exhibited significant antibacterial activity. The in vitro results reported here suggest that, for patients suffering from bacterial throat infections, if aromatherapy is used, these essential oils, considered as potential antimicrobial agents, should be preferred. PMID:23662123

Sfeir, Julien; Lefrançois, Corinne; Baudoux, Dominique; Derbré, Séverine; Licznar, Patricia

2013-01-01

351

New antibacterial agents: patent applications published in 2010.  

PubMed

This review summarizes patent applications from 2010 for small molecules for which there is a claim of antibacterial activity. The primary criterion for inclusion in this analysis was reporting of cellular antibacterial activity data (MICs) for at least one compound. Patent applications are reviewed according to their biological target and antibacterial class. Protein synthesis inhibitors disclosed in this period include inhibitors of the 50S ribosome subunit (oxazolidinones, macrolides/ketolides and pleuromutilins), 30S ribosome subunit (aminoglycosides and tetracyclines) and nonribosomal targets (PDF inhibitors). DNA synthesis inhibitors include inhibitors of GyrA/ParC and GyrB/ParE. Cell envelope disruptors disclosed in 2010 cover both inhibitors of cell-envelope synthesis (LpxC inhibitors, ?-lactams and glycopeptides), as well as membrane disruptors (lipopeptides and polymyxins). Other antibacterial classes covered in this review include rifamycins and antibacterial peptides. Patent applications for compounds aimed at overcoming resistance mechanisms (efflux inhibitors and ?-lactamase inhibitors) are also described. PMID:24236928

Stokes, Suzanne S; Morningstar, Marshall; Kocis, Helena; Verheijen, Jeroen C

2012-11-01

352

Tricyclic GyrB/ParE (TriBE) Inhibitors: A New Class of Broad-Spectrum Dual-Targeting Antibacterial Agents  

PubMed Central

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models. PMID:24386374

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael; Bensen, Daniel C.; Chen, Zhiyong; Lam, Thanh; Zhang, Junhu; Lee, Suk Joong; Hough, Grayson; Phillipson, Doug; Akers-Rodriguez, Suzanne; Cunningham, Mark L.; Kwan, Bryan P.; Nelson, Kirk J.; Castellano, Amanda; Locke, Jeff B.; Brown-Driver, Vickie; Murphy, Timothy M.; Ong, Voon S.; Pillar, Chris M.; Shinabarger, Dean L.; Nix, Jay; Lightstone, Felice C.; Wong, Sergio E.; Nguyen, Toan B.; Shaw, Karen J.; Finn, John

2013-01-01

353

Antibacterial anthranilic acid derivatives from Geijera parviflora.  

PubMed

Five anthranilic acid derivatives, a mixture I of three new compounds 11'-hexadecenoylanthranilic acid (1), 9'-hexadecenoylanthranilic acid (2), and 7'-hexadecenoylanthranilic acid (3), as well as a new compound 9,12,15-octadecatrienoylanthranilic acid (4) together with a new natural product, hexadecanoylanthranilic acid (5), were isolated from Geijera parviflora Lindl. (Rutaceae). Their structures were elucidated by extensive spectroscopic measurements, and the positions of the double bonds in compounds 1-3 of the mixture I were determined by tandem mass spectrometry employing ozone-induced dissociation. The mixture I and compound 5 showed good antibacterial activity against several Gram-positive strains. PMID:24370663

Shou, Qingyao; Banbury, Linda K; Maccarone, Alan T; Renshaw, Dane E; Mon, Htwe; Griesser, Stefani; Griesser, Hans J; Blanksby, Stephen J; Smith, Joshua E; Wohlmuth, Hans

2014-03-01

354

Multiresidue determination of (fluoro)quinolone antibiotics in chicken by polymer monolith microextraction and field-amplified sample stacking procedures coupled to CE-UV  

Microsoft Academic Search

Simultaneous determination of 9 (fluoro)quinolone antibiotics (FQs) was accomplished by capillary electrophoresis-ultraviolet (CE-UV) based on poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith microextraction (PMME) coupled with on-line preconcentration technique of field-amplified sample stacking (FASS). The effects of composition of the acid and organic solvent in the sample solution, sampling time, and voltage on the efficiency of the sample stacking have been

Hai-Bo He; Xiao-Xia Lv; Qiong-Wei Yu; Yu-Qi Feng

2010-01-01

355

Quinolone-resistant Escherichia coli O127a:K63 serotype with an extended-spectrum-beta-lactamase phenotype from a food poisoning outbreak in China.  

PubMed

We report an atypical enteropathogenic Escherichia coli O127a:K63 strain with resistance to quinolones and extended-spectrum cephalosporins isolated from a 2010 food poisoning outbreak involving 112 adults in China. Two resistance genes [bla(CTX-M-15), aac(6')-Ib-c] and five mutations (two in gyrA, two in parC, one in parE) coexisted in this enteropathogenic E. coli strain. PMID:22553233

Hao, Rongzhang; Qiu, Shaofu; Wang, Yong; Yang, Guang; Su, Wenli; Song, Lixue; Zhang, Jia; Chen, Jiaxu; Jia, Leili; Wang, Ligui; Song, Hongbin

2012-07-01

356

Complete Nucleotide Sequence of pK245, a 98Kilobase Plasmid Conferring Quinolone Resistance and Extended-Spectrum- Lactamase Activity in a Clinical Klebsiella pneumoniae Isolate  

Microsoft Academic Search

A plasmid containing the qnrS quinolone resistance determinant and the gene encoding the SHV-2 -lactamase has been discovered from a clinical Klebsiella pneumoniae strain isolated in Taiwan. The complete 98-kb sequence of this plasmid, designated pK245, was determined by using a whole-genome shotgun approach. Transfer of pK245 conferred low-level resistance to fluoroquinolones in electroporant Escherichia coli epi300. The sequence of

Ying-Tsong Chen; Hung-Yu Shu; Ling-Hui Li; Tsai-Lien Liao; Keh-Ming Wu; Yih-Ru Shiau; Jing-Jou Yan; Ih-Jen Su; Shih-Feng Tsai; Tsai-Ling Lauderdale

2006-01-01

357

Comparison of the in vitro activities of Bay 12-8039, a new quinolone, and other antimicrobials against clinically important anaerobes.  

PubMed Central

Bay 12-8039, a new 8-methoxy quinolone, was compared with other agents for activity against clinically relevant anaerobes. Bay 12-8039 inhibited 91 and 96% of the 410 test isolates at 2 and 4 micrograms/ml, respectively. Bay 12-8039 had activity comparable to that metronidazole and overall was at least 16-fold more active than ciprofloxacin, ofloxacin, and cefoxitin, 32-fold more active than cefotetan, and at least 128-fold more active than penicillin G. PMID:9056020

Aldridge, K E; Ashcraft, D S

1997-01-01

358

Quinolone-Resistant Escherichia coli O127a:K63 Serotype with an Extended-Spectrum-Beta-Lactamase Phenotype from a Food Poisoning Outbreak in China  

PubMed Central

We report an atypical enteropathogenic Escherichia coli O127a:K63 strain with resistance to quinolones and extended-spectrum cephalosporins isolated from a 2010 food poisoning outbreak involving 112 adults in China. Two resistance genes [blaCTX-M-15, aac(6?)-Ib-c] and five mutations (two in gyrA, two in parC, one in parE) coexisted in this enteropathogenic E. coli strain. PMID:22553233

Hao, Rongzhang; Qiu, Shaofu; Yang, Guang; Su, Wenli; Song, Lixue; Zhang, Jia; Chen, Jiaxu; Jia, Leili; Wang, Ligui

2012-01-01

359

In vitro activity of quinupristin\\/dalfopristin and newer quinolones combined with gentamicin against resistant isolates of Enterococcus faecalis and Enterococcus faecium  

Microsoft Academic Search

In a study designed to obtain data on compounds active against enterococci, the minimum inhibitory concentrations (MICs) of quinupristin\\/dalfopristin (RP 59500) and the novel quinolones DU-6859a, trovafloxacin, levofloxacin, and sparfloxacin were determined for 122Enterococcus faecalis and sevenEnterococcus faecium isolates. In addition, 15Enterococcus faecalis isolates resistant to gentamicin, DU-6859a, and trovafloxacin were exposed over time to combinations of DU-6859a plus gentamicin

E. J. Giamarellos-Bourboulis; H. Sambatakou; P. Grecka; H. Giamarellou

1998-01-01

360

In Vitro Activity of Quinupristin\\/Dalfopristin and Newer Quinolones Combined with Gentamicin against Resistant Isolates of Enterococcus faecalis and Enterococcus faecium  

Microsoft Academic Search

In a study designed to obtain data on compounds active against enterococci, the minimum inhibitory concentrations (MICs) of quinupristin\\/dalfopristin (RP 59500) and the novel quinolones DU-6859a, trovafloxacin, levofloxacin, and sparfloxacin were determined for 122 Enterococcus faecalis and seven Enterococcus faecium isolates. In addition, 15 Enterococcus faecalis isolates resistant to gentamicin, DU-6859a, and trovafloxacin were exposed over time to combinations of

E. J. Giamarellos-Bourboulis; H. Sambatakou; P. Grecka; H. Giamarellou

1998-01-01

361

Discrepancy between minimal inhibitory concentration to enrofloxacin and mutations present in the quinolone-resistance determining regions of Mycoplasma gallisepticum field strains.  

PubMed

Molecular characterization of the quinolone-resistance determining regions (QRDRs) of DNA gyrase and topoisomerase IV in 93 Mycoplasma gallisepticum field strains isolated in different geographic regions revealed discrepancies between minimal inhibitory concentration values and presence of amino acid substitutions within the QRDRs of GyrA and ParC in 9/93 (10%) strains. This may delimitate applicability of a gene-based assay to detect fluoroquinolone resistance in this avian pathogen. PMID:22655973

Lysnyansky, I; Gerchman, I; Levisohn, S; Mikula, I; Feberwee, A; Ferguson, N M; Noormohammadi, A H; Spergser, J; Windsor, H M

2012-11-01

362

Suppressive effect of 2-phenyl-4-quinolone (YT 1) on hind-paw edema and cutaneous vascular plasma extravasation in mice  

Microsoft Academic Search

Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48\\/80-induced mouse ear edema was suppressed

Jih-Pyang Wang; Mei-Feng Hsu; Shue-Ling Raung; Sheng-Chu Kuo

1994-01-01

363

In vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci  

Microsoft Academic Search

Tigecycline is a glycylcycline with promising broad-spectrum activity, including resistant Gram-positive organisms. This study characterizes in vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae (QRSP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). An in vitro pharmacodynamic model generated specific bacterial kill profiles for tigecycline against clinical isolates of QRSP, MRSA and VRE. Tigecycline produced a 6.6log total reduction

Mark W. Garrison; Joshua J. Nuemiller

2007-01-01

364

Effects of DQ113, a New Quinolone, against Methicillin- and Vancomycin-Resistant Staphylococcus aureus-Caused Hematogenous Pulmonary Infections in Mice  

Microsoft Academic Search

We compared the effects of DQ-113, a new quinolone, to those of vancomycin (VCM) and teicoplanin (TEIC) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA). The MICs of DQ-113, VCM, and TEIC for MRSA were 0.125, 1.0, and 0.5 g\\/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0

Yukihiro Kaneko; Katsunori Yanagihara; Yoshitsugu Miyazaki; Kazuhiro Tsukamoto; Yoichi Hirakata; Kazunori Tomono; Jun-ichi Kadota; Takayoshi Tashiro; Ikuo Murata; Shigeru Kohno

2003-01-01

365

Terrestrial actinomycetes from diverse locations of Uttarakhnad, India: Isolation and screening for their antibacterial activity  

PubMed Central

Background and Objective Uttarakhand region is less explored, but possess a great biodiversity. This diversity can be explored for isolation and characterization of new actinomycetes strains for seeking antimicrobial molecules. It can therefore be predicted that novel bioactive metabolite producing actinomycetes can be discovered to combat multidrug resistant bacterial pathogens. Materials and Methods Variations in the viable count of actinomycetes were accessed in different altitudes. Actinomycetes were isolated, indentified and screened for their antibacterial activity. Results The highest viable counts of actinomycetes were recorded in valleys followed by mid hills and high hills. A total of 512 actinomycetes were isolated which were found to belong the 14 different genera of actinomycetes. Mainly the genus Streptomyces was dominant in all the soil samples. Out of 512 isolates recovered, 23.44% exhibited antibacterial activity against one or more tested bacterial pathogens. Of these 56.67% showed activity against Gram-positive bacteria, 26.67% against Gram-negative bacteria while 16.67% showed broad spectrum activity. Isolate DV1S and GR9a-5 showed highest antibacterial properties against several multi-drug resistant bacterial pathogens and were identified using polyphasic approach. DV1S and GR9a-5 were found to be most closely related with S. massasporeus NBRC 12796T and Nocardia nova JCM 6044T respectively. Conclusion The results of this study strongly support the idea that the viable count of actinomycetes varied greatly with altitude. The actinomycetes species isolated from valleys, mid hills and high hills possess significant capacity to produce compounds which are active against several drug resistant bacterial pathogens. PMID:24475340

Kumar, Vijay; Bisht, Gajraj Singh; Gusain, Omprakash

2013-01-01

366

Structural insights into quinolone antibiotic resistance mediated by pentapeptide repeat proteins: conserved surface loops direct the activity of a Qnr protein from a Gram-negative bacterium  

PubMed Central

Quinolones inhibit bacterial type II DNA topoisomerases (e.g. DNA gyrase) and are among the most important antibiotics in current use. However, their efficacy is now being threatened by various plasmid-mediated resistance determinants. Of these, the pentapeptide repeat-containing (PRP) Qnr proteins are believed to act as DNA mimics and are particularly prevalent in Gram-negative bacteria. Predicted Qnr-like proteins are also present in numerous environmental bacteria. Here, we demonstrate that one such, Aeromonas hydrophila AhQnr, is soluble, stable, and relieves quinolone inhibition of Escherichia coli DNA gyrase, thus providing an appropriate model system for Gram-negative Qnr proteins. The AhQnr crystal structure, the first for any Gram-negative Qnr, reveals two prominent loops (1 and 2) that project from the PRP structure. Deletion mutagenesis demonstrates that both contribute to protection of E. coli DNA gyrase from quinolones. Sequence comparisons indicate that these are likely to be present across the full range of Gram-negative Qnr proteins. On this basis we present a model for the AhQnr:DNA gyrase interaction where loop1 interacts with the gyrase A ‘tower’ and loop2 with the gyrase B TOPRIM domains. We propose this to be a general mechanism directing the interactions of Qnr proteins with DNA gyrase in Gram-negative bacteria. PMID:21227918

Xiong, Xiaoli; Bromley, Elizabeth H. C.; Oelschlaeger, Peter; Woolfson, Derek N.; Spencer, James

2011-01-01

367

Simultaneous Quantification of Limonin, Two Indolequinazoline Alkaloids, and Four Quinolone Alkaloids in Evodia rutaecarpa (Juss.) Benth by HPLC-DAD Method  

PubMed Central

A simple and efficient HPLC-DAD (225?nm) method was developed and validated for the simultaneous determination of limonin and six key alkaloids (evodiamine, rutaecarpine, 1-methyl-2-undecyl-4(1H)-quinolone, evocarpine, 1-methy-2-[(6Z,9Z)]-6,9-pentadecadienyl-4-(1H)-quinolone, and dihydroevocarpine) in Evodia rutaecarpa (Juss.) Benth, which has been widely used as one of the Traditional Chinese Medicines. The chromatographic separation was carried out on a Hypersil BDS C18 column, and gradient elution was employed with a mobile phase containing acetonitrile and water. Contents of the analytes in 18 batches of samples were analyzed by ultrasonic extraction with ethanol and water mixture (80?:?20, v/v) followed by HPLC analysis. Separation of the seven analytes was achieved within 60?min with good linearity (r > 0.999). The RSD of both the intraday and interday precision was below 1.85%. The accuracy at different concentrations was within the range of 97.91 to 100.49%. Hierarchical clustering analysis was performed to differentiate and classify the samples based on the contents of the seven constituents. This study indicated that the quality control of E. rutaecarpa could be simplified to the measurement of four constituents, and that limonin, 1-methyl-2-undecyl-4(1H)-quinolone, and dihydroevocarpine should also be served as the chemical markers together with evodiamine for the quality control of Evodia rutaecarpa (Juss.) Benth. PMID:23738236

Zhang, Pei-ting; Pan, Bi-yan; Liao, Qiong-feng; Yao, Mei-cun; Xu, Xin-jun; Wan, Jin-zhi; Liu, Dan; Xie, Zhi-yong

2013-01-01

368

Quinolone-resistant Escherichia coli isolated from birds of prey in Portugal are genetically distinct from those isolated from water environments and gulls in Portugal, Spain and Sweden.  

PubMed

The influence of geographic distribution and type of habitat on the molecular epidemiology of ciprofloxacin resistant Escherichia coli was investigated. Ciprofloxacin resistant E. coli from wastewater, urban water with faecal contamination and faeces of gulls, pigeons and birds of prey, from Portugal, Spain and Sweden were compared based on multi-locus sequence typing (MLST) and quinolone resistance genetic determinants. Multi-locus sequence typing allowed the differentiation of E. coli lineages associated with birds of prey from those inhabiting gulls and waters. E. coli lineages of clinical relevance, such as the complex ST131, were detected in wastewater, streams and gulls in Portugal, Spain and Sweden. Quinolone resistance was due to gyrA and parC mutations, although distinct mutations were detected in birds of prey and in wastewater, streams and gulls isolates. These differences were correlated with specific MLST lineages, suggesting resistance inheritance. Among the plasmid-mediated quinolone resistance genes, only aac(6')-ib-cr and qnrS were detected in wastewater, streams and gulls isolates, but not in birds of prey. The horizontal transfer of the gene aac(6')-ib-cr could be inferred from its occurrence in different MLST lineages. PMID:24034690

Vredenburg, Jana; Varela, Ana Rita; Hasan, Badrul; Bertilsson, Stefan; Olsen, Björn; Narciso-da-Rocha, Carlos; Bonnedahl, Jonas; Stedt, Johan; Da Costa, Paulo Martins; Manaia, Célia M

2014-04-01

369

The Effect of Antibacterial Formula Hand Cleaners on the Elimination of Microbes on Hands  

Microsoft Academic Search

: The purpose of this project is to find out which one of the antibacterial hand cleanser (antibacterial bar soap, antibacterial liquid hand soap, and liquid hand sanitizer) is more effective in eliminating microbes. If antibacterial- formula liquid hand soap is used on soiled hands, then it will be more effective in eliminating microbes. Germs are microorganisms that cause disease

J. R. Coleman

2002-01-01

370

Investigation of antibacterial activity of cotton fabric incorporating nano silver colloid  

Microsoft Academic Search

In this work, silver nanoparticles were prepared by polyol process with microwave heating and incorporated on cotton fabric surfaces. The antibacterial performance of the antibacterial cotton fabric was tested for different concentration of nano-sized silver colloid, contact time germs, and washing times. It was found that antibacterial activity increased with the increasing concentration of nano-sized silver colloid. The antibacterial fabric

Ngo Vo Ke Thanh; Nguyen Thi Phuong Phong

2009-01-01

371

Antibacterial activity of sucralfate versus aluminum chloride in simulated gastric fluid  

Microsoft Academic Search

Studies have previously demonstrated that sucralfate possesses intrinsic antibacterial activity. This study was designed to indirectly assess whether aluminum is the active antibacterial component of sucralfate and to further evaluate factors that may influence this agent's antibacterial activity. Utilizing an in vitro model, the antibacterial activity of sucralfate, an equivalent quantity of aluminum in the form of aluminum chloride, and

L. Welage; P. Carver; K. Welch

1994-01-01

372

Preparation of active antibacterial LDPE surface through multistep physicochemical approach: I. Allylamine grafting, attachment of antibacterial agent and antibacterial activity assessment  

Microsoft Academic Search

Low-density polyethylene (LDPE) samples were treated in air plasma discharge, coated by polyallyamine brush thought copolymeric grafting surface-from reaction and deposited four common antibacterial agents (benzalkonium chloride, bronopol, chlorhexidine and triclosan) to gain material with active antibacterial properties. Surface characteristics were evaluated by static contact angle measurement with surface energy evaluation ATR-FTIR, X-ray Photoelectron Spectroscopy (XPS) and SEM analysis. Inhibition

František Bílek; Tá?a K?ížová; Marián Lehocký

2011-01-01

373

An In Vitro Study on the Effects of Nisin on the Antibacterial Activities of 18 Antibiotics against Enterococcus faecalis  

PubMed Central

Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (p<0.05). The checkerboard assay showed that the combination of nisin and penicillin or chloramphenicol had a synergetic effect against the three tested E. faecalis strains. The transmission electron microscope images showed that E. faecalis was not obviously destroyed by penicillin or chloramphenicol alone but was severely disrupted by either antibiotic in combination with nisin. Furthermore, assessing biofilms by a confocal laser scanning microscope showed that penicillin, ciprofloxacin, and chloramphenicol all showed stronger antibiofilm actions in combination with nisin than when these antibiotics were administered alone. Therefore, nisin can significantly improve the antibacterial and antibiofilm activities of many antibiotics, and certain antibiotics in combination with nisin have considerable potential for use as inhibitors of this drug-resistant pathogen. PMID:24586598

Ling, Junqi; Ma, Jinglei; Huang, Lijia; Zhang, Luodan

2014-01-01

374

Isolation and identification of a potent antimalarial and antibacterial polyacetylene from Bidens pilosa.  

PubMed

Diseases caused by malaria parasites and pathogenic bacteria were thought to be on the brink of eradication in the 1950-1960s, but they have once again become a serious threat to mankind as a result of the appearance of multidrug resistant strains. The spread of these multidrug resistant organisms has prompted a worldwide search for new classes of effective antimalarial and antibacterial drugs. Natural products have been recognized as highly important candidates for this purpose. Our attention has focused on the herbal plant Bidens pilosa, a weed common throughout the world, as one of the target plants in the search for new active compounds, owing to its empirical use in the treatment of infectious diseases and to pharmaco-chemical studies of its crude extract. We report the isolation of two new compounds of B. pilosa, the linear polyacetylenic diol 1 and its glucoside 2 which have previously been isolated from different plants. Compound 1 exhibited highly potent antimalarial and antibacterial properties in vitro as well as potent antimalarial activity by way of intravenous injection in vivo, thereby representing a promising new class of drugs potentially effective in the treatment of malarial and bacterial diseases. We suspect that discovery of these compounds in B. pilosa in appreciable quantity is because the Fijian tradition of using the fresh plant for extraction rather than the Asian tradition of using dried plants (1 is unstable in the dried state) was followed. PMID:19263339

Tobinaga, Seisho; Sharma, Mukesh K; Aalbersberg, William G L; Watanabe, Kinzo; Iguchi, Kazuo; Narui, Koji; Sasatsu, Masanori; Waki, Seizi

2009-05-01

375

Comparative analysis of viperidae venoms antibacterial profile: a short communication for proteomics.  

PubMed

Bacterial infections involving multidrug-resistant strains are one of the ten leading causes of death and an important health problem in need for new antibacterial sources and agents. Herein, we tested and compared four snake venoms (Agkistrodon rhodostoma, Bothrops jararaca, B. atrox and Lachesis muta) against 10 Gram-positive and Gram-negative drug-resistant clinical bacteria strains to identify them as new sources of potential antibacterial molecules. Our data revealed that, as efficient as some antibiotics currently on the market (minimal inhibitory concentration (MIC) = 1-32 ?g mL(-1)), A. rhodostoma and B. atrox venoms were active against Staphylococcus epidermidis and Enterococcus faecalis (MIC = 4.5 ?g mL(-1)), while B. jararaca inhibited S. aureus growth (MIC = 13 ?g ml(-1)). As genomic and proteomic technologies are improving and developing rapidly, our results suggested that A. rhodostoma, B. atrox and B. jararaca venoms and glands are feasible sources for searching antimicrobial prototypes for future design new antibiotics against drug-resistant clinical bacteria. They also point to an additional perspective to fully identify the pharmacological potential of these venoms by using different techniques. PMID:18955360

Ferreira, Bruno L; Santos, Dilvani O; Dos Santos, André Luis; Rodrigues, Carlos R; de Freitas, Cícero C; Cabral, Lúcio M; Castro, Helena C

2011-01-01

376

Light-activated antibacterial surfaces comprise photosensitizers.  

PubMed

Antibacterial surfaces were prepared using a base polyethylene sheet topped with a layer containing a mixed powder of poly (vinylidene fluoride) and photosensitizers (PSs). A crimpled stamp was placed on the mixed powder, and then it was passed through a heating and pressing device. The three chosen PSs were rose bengal, toluidine blue O and methylene blue. Scanning electron microscope analysis showed that the PS surface texture was coarse and highly developed. Measurement of the apparent contact angles of the droplets deposited on the PS surfaces using goniometry showed that all three surfaces were hydrophobic. Photodynamic analysis of the surfaces into which the PSs were incorporated indicated significant reactive oxygen species formation after illumination with light fluency rate of 1.46 mW cm(-2) for 30 min. Photodynamic inactivation assays performed in nutrient broth demonstrated more than 4 log reduction of the attached Escherichia coli after illumination (1.46 mW cm(-2)) for 24 h when the inoculum was 10(3) CFU mL(-1). However, more than 4 log reduction of Staphylococcus aureus occurred even when the cultures were illuminated for only 6 h. Our results provide an inexpensive, simple, state-of-the-art method for preparing antibacterial surfaces that may help prevent infections in hospital surroundings and in some medical devices. PMID:21883241

Cahan, Rivka; Schwartz, Ronen; Langzam, Yakov; Nitzan, Yeshayahu

2011-01-01

377

[Thrombin inhibitors which display antibacterial activity].  

PubMed

The investigation of cytotoxicity and antibacterial activity of the novel thrombin inhibitors containing retro-D-sequences -D-Arg-D-Phe--modified by D-arginine amino group by the residues of lauric acid or chromone-contained substituent, in comparison with known cationic preservative Nalpha-lauroyl-L-arginine ethyl ester (LAE) have been carried out. It has been shown that compound Laur-D-Arg-D-Phe-OMe has a similar cytotoxicity with LAE, and Chrom-D-Arg-D-Phe-OMe has almost twice higher toxicity than it fatty moiety contained analogues. Antibacterial activity of Laur-D-Arg-D-Phe-OMe against Staphylococcus aureus and Bacillus subtilis is close in action to LAE. It is assumed that ability of thrombin inhibitors to suppress the growth of some microorganisms can be explained by their ability to suppress activity of trypsin-like serine proteinases, which participate in the infection process of Staphylococcus aureus and influence on Bacillus subtilis sporulation. These findings open new prospects for exploring efficient antimicrobial agents among synthetic low-molecular trypsin-like serine proteinase inhibitors. PMID:20684237

Poiarkov, A A; Timoshok, N A; Spivak, N Ia; Poiarkova, S A

2010-01-01

378

Antibacterial Nitroacridine, Nitroakridin 3582: Effects on Bacterial Growth and Macromolecular Biosynthesis In Vivo  

PubMed Central

The antibacterial drug Nitroakridin 3582 inhibited the growth of selected grampositive bacteria more strongly than it inhibited the growth of gram-negative bacilli. Nitroakridin at concentrations of the order of 5 × 10?5m induced lysis of Bacillus licheniformis and Micrococcus lysodeikticus. At concentrations less than 10?4m, Nitroakridin 3582 reduced the exponential growth rate of Escherichia coli C-2; at 10?4m the drug was bacteriostatic, and, at concentrations greater than 10?4m, it was bactericidal. Prolonged bacteriostasis resulted in the formation of long filaments by E. coli, Serratia marcescens, Shigella sonnei, and Proteus mirabilis. The reversible effects of Nitroakridin 3582 on the growth of E. coli correlated with partial inhibitions of deoxyribonucleic acid biosynthesis; ribonucleic acid and protein syntheses were inhibited less strongly. Nitroakridin 3582 at concentrations greater than 2 × 10?4m, which block deoxyribonucleic acid biosynthesis, produced an accelerated bactericidal action. Images PMID:4941562

Wolfe, Alan D.; Cook, Thomas M.; Hahn, Fred E.

1971-01-01

379

Electrospun antibacterial polyurethane-cellulose acetate-zein composite mats for wound dressing.  

PubMed

In this study, an antibacterial electrospun nanofibrous scaffolds with diameters around 400-700 nm were prepared by physically blending polyurethane (PU) with two biopolymers such as cellulose acetate (CA) and zein. Here, PU was used as the foundation polymer, was blended with CA and zein to achieve desirable properties such as better hydrophilicity, excellent cell attachment, proliferation and blood clotting ability. To prevent common clinical infections, an antimicrobial agent, streptomycin sulfate was incorporated into the electrospun fibers and its antimicrobial ability against the gram negative and gram positive bacteria were examined. The interaction between fibroblasts and the PU-CA and PU-CA-zein-drug scaffolds such as viability, proliferation, and attachment were characterized. PU-CA-zein-drug composite nanoscaffold showed enhanced blood clotting ability in comparison with pristine PU nanofibers. The presence of CA and zein in the nanofiber membrane improved its hydrophilicity, bioactivity and created a moist environment for the wound, which can accelerate wound recovery. PMID:24507360

Unnithan, Afeesh Rajan; Gnanasekaran, Gopalsamy; Sathishkumar, Yesupatham; Lee, Yang Soo; Kim, Cheol Sang

2014-02-15

380

Drug allergies  

MedlinePLUS

Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... vomiting to life-threatening anaphylaxis . A true drug allergy is caused by a series of chemical steps ...

381

Isolation, identification, and quantification of roasted coffee antibacterial compounds.  

PubMed

Coffee brew is a widely consumed beverage with multiple biological activities due both to naturally occurring components and to the hundreds of chemicals that are formed during the roasting process. Roasted coffee extract possesses antibacterial activity against a wide range of microorganisms, including Staphylococcus aureus and Streptococcus mutans, whereas green coffee extract exhibits no such activity. The naturally occurring coffee compounds, such as chlorogenic acids and caffeine, cannot therefore be responsible for the significant antibacterial activity exerted by coffee beverages against both bacteria. The very low minimum inhibitory concentration (MIC) found for standard glyoxal, methylglyoxal, and diacetyl compounds formed during the roasting process points to these alpha-dicarbonyl compounds as the main agents responsible for the antibacterial activity of brewed coffee against Sa. aureus and St. mutans. However, their low concentrations determined in the beverage account for only 50% of its antibacterial activity. The addition of caffeine, which has weak intrinsic antibacterial activity, to a mixture of alpha-dicarbonyl compounds at the concentrations found in coffee demonstrated that caffeine synergistically enhances the antibacterial activity of alpha-dicarbonyl compounds and that glyoxal, methylglyoxal, and diacetyl in the presence of caffeine account for the whole antibacterial activity of roasted coffee. PMID:18001036

Daglia, Maria; Papetti, Adele; Grisoli, Pietro; Aceti, Camilla; Spini, Valentina; Dacarro, Cesare; Gazzani, Gabriella

2007-12-12

382

Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive gellan system  

PubMed Central

Background and the purpose of the study The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of mucoadhesive in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac and have good mucoadhesion with ocular mucus layers. The objective of this study was to formulate ophthalmic mucoadhesive system of gatifloxacin (GTN) and to evaluate its in vitro antibacterial potential against, Staphylococcus aureus and Escherichia coli. Methods : Mucoadhesive systems were prepared using gellan combined with sodium carboxymethylcellulose (NaCMC) or sodium alginate to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their gelation, and rheological behaviors, mucoadhesion force, in vitro drug release, and antibacterial activity. Results All formulations in non-physiological or physiological conditions showed pseudoplastic behaviors. Increase in the concentration of mucoadhesive agent enhanced the mucoadhesive force significantly. In vitro release of gatifloxacin from the mucoadhesive system in simulated tear fluid (STF, pH of 7.4) was influenced significantly by the properties and concentration of gellan, sodium carboxymethyl cellulose and sodium alginate. Significant reduction in the total bacterial count was observed between drug solution (control) and mucoadhesive batches against both tested organisms. Major conclusion The developed mucoadhesive system is a viable alternative to conventional eye drops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug. PMID:22615622

Kesavan, K.; Nath, G.; Pandit, JK.

2010-01-01

383

Synthesis and Antibacterial Activities of Antibacterial Peptides with a Spiropyran Fluorescence Probe  

PubMed Central

In this report, antibacterial peptides1-3 were prepared with a spiropyran fluorescence probe. The probe exhibits a change in fluorescence when isomerized from a colorless spiro-form (spiropyran, Sp) to a colored open-form (merocyanine, Mc) under different chemical environments, which can be used to study the mechanism of antimicrobial activity. Peptides 1-3 exhibit a marked decrease in antimicrobial activity with increasing alkyl chain length. This is likely due to the Sp-Mc isomers in different polar environments forming different aggregate sizes in TBS, as demonstrated by time-dependent dynamic light scattering (DLS). Moreover, peptides 1-3 exhibited low cytotoxicity and hemolytic activity. These probe-modified peptides may provide a novel approach to study the effect of structural changes on antibacterial activity, thus facilitating the design of new antimicrobial agents to combat bacterial infection. PMID:25358905

Chen, Lei; Zhu, Yu; Yang, Danling; Zou, Rongfeng; Wu, Junchen; Tian, He

2014-01-01

384

Purification and characterization of an antibacterial factor from snail mucus.  

PubMed

The antibacterial factor from the body surface of the African giant snail, Achatina fulica Férussac, was isolated by DEAE-Toyopearl 650M ion exchange chromatography. The isolated preparation exhibited highly positive antibacterial activity both for the Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus and for the Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, but it lost such activity when heated at 75 degrees C for 5 min. The antibacterial factor of the snail mucus was a glycoprotein whose molecular weight (MW) was about 160,000. It was composed of two subunits of MW 70,000-80,000. PMID:2866907

Kubota, Y; Watanabe, Y; Otsuka, H; Tamiya, T; Tsuchiya, T; Matsumoto, J J

1985-01-01

385

Antibacterial therapy of neurosyphilis: lack of impact of new therapies.  

PubMed

Neurosyphilis is caused by the spirochete Treponema pallidum. These organisms divide slowly, requiring long exposure to antibacterials for treatment success. In order for an antibacterial to be effective in the therapy of neurosyphilis, it must achieve treponemicidal concentrations in the CSF, have a long half-life and be given in a treatment regimen that favours compliance. Penicillin was first introduced for the treatment of syphilis in 1943, and despite interest in the use of amoxicillin, erythromycin, tetracycline, doxycycline, ceftriaxone and azithromycin, penicillin remains the only recommended antibacterial agent for neurosyphilis. PMID:12421113

Ali, Latisha; Roos, Karen L

2002-01-01

386

Bay Y 3118, a new quinolone derivative, rapidly eradicates Listeria monocytogenes from infected mice and L929 cells.  

PubMed Central

Bay Y 3118 is a new quinolone derivative with pronounced activity against gram-positive bacteria including the facultatively intracellular bacterium Listeria monocytogenes. Bay Y 3118 was tested in vitro and in animal models of listeriosis. All strains of L. monocytogenes and other Listeria spp. were highly susceptible in vitro; the MICs for these organisms ranged from 0.062 to 0.25 micrograms/ml. Bay Y 3118 was rapidly bactericidal in vitro, with a postantibiotic effect occurring for 3 h after removal of the antibiotic. L. monocytogenes was eliminated from infected L929 cells treated with Bay Y 3118, suggesting a bactericidal effect on the listeriae in these cells. Immunocompetent mice were rapidly cured by treatment with 4 mg every 12 h. Concomitantly, the levels of interleukin 6 and gamma interferon in mouse sera declined rapidly. In immunocompetent mice, treatment with 2 mg of Bay Y 3118 every 12 h resulted in a greater initial reduction in the listerial counts in the organs than treatment with 2 mg of ampicillin every 12 h. Bay Y 3118 completely eliminated L. monocytogenes from the livers and spleens of chronically infected nude mice. However, some of the bacteria reappeared after the cessation of therapy. In conclusion, Bay Y 3118 is an excellent candidate substance for the therapy of infections caused by facultatively intracellular gram-positive bacteria such as L. monocytogenes. Images PMID:7979279

Nichterlein, T; Kretschmar, M; Budeanu, C; Bauer, J; Linss, W; Hof, H

1994-01-01

387

[Growing incidence of nalidixic acid resistance and sensitivity to quinolones in Salmonella typhimurium strains isolated from man or animal].  

PubMed

To determine the prevalence of quinolone resistance in Salmonella typhimurium strains from humans or animals (cattle, poultry, swine), the S. typhimurium strains isolated at a teaching hospital and at the central veterinary laboratory of the same district between January 1, 1995, and December 31, 1996 were studied. Susceptibility to nalidixic acid was determined using the disk diffusion method. Strains with decreased susceptibility to nalidixic acid were subjected to minimal inhibitory concentration (MIC) determination for pefloxacin, ofloxacin, ciprofloxacin, norfloxacin, levofloxacin, and grepafloxacin. Decreased susceptibility to nalidixic acid was demonstrated for 41 of the 309 strains studied and increased from 8.5% in 1995 to 18.6% in 1996. MIC90 values of fluoroquinolones for strains with decreased susceptibility to nalidixic acid were lower than 1 mg/L, which is the cutoff above which a strain is classified as susceptible, but were higher than for strains that were susceptible to nalidixic acid. These low levels of resistance may be the first step in selection of mutant strains with high levels of resistance to fluoroquinolones. This warrants continued monitoring of resistance of Salmonella to fluoroquinolones. PMID:9871929

Heurtin-Le Corre, C; Donnio, P Y; Bonnier, M; Travert, M F; Lacourt, A; Avril, J L

1998-10-01

388

Evaluation of antibacterial and anthelmintic activities with total phenolic contents of Piper betel leaves  

PubMed Central

Objective: The study was conducted to investigate the antibacterial and anthelmintic activities and to determine total phenolic contents of methanolic extract of Piper betel leaves. Materials and Methods: The extract was subjected to assay for antibacterial activity using both gram positive and gram negative bacterial strains through disc diffusion method; anthelmintic activity with the determination of paralysis and death time using earthworm (Pheritima posthuma) at five different concentrations and the determination of total phenolic contents using the Folin-ciocalteau method. Results: The extract showed significant (p<0.01) zone of inhibitions against gram positive Staphylococcus aureus [(6.77±0.25) mm] and Gram negative Escherichia coli [(8.53±0.25) mm], Salmonella typhi [(5.20±0.26) mm], Shigella dysenteriae [(11.20±0.26) mm] compared to positive control Azithromycin (ranging from 20.10±0.17 to 25.20±0.35 mm) while no zone inhibitory activity was found for both the extract and the standard drug against Gram positive Bacillus cereus. The extract also showed potent anthelmintic activity requiring less time for paralysis and death compared to the standard drug albendazole (10 mg/ml). At concentrations 10, 20, 40, 60 and 80 mg/ml, leaves extract showed paralysis at mean time of 9.83±0.60, 8.50±0.29, 6.60±0.17, 6.20±0.44 and 4.16±0.60; death at 11.33±0.88, 9.67±0.33, 7.83±0.17, 7.16±0.60 and 5.16±0.72 minutes, respectively. Whereas the standard drug showed paralysis and death at 19.33±0.71 and 51.00±0.23 minutes respectively. The extract confirmed the higher concentration of phenolic contents (124.42±0.14 mg of GAE /g of extract) when screened for total phenolic compounds. Conclusion: As results confirmed potential antibacterial and anthelmintic activities of Piper betel leaves extract, therefore it may be processed for further drug research. PMID:25386394

Akter, Kazi Nahid; Karmakar, Palash; Das, Abhijit; Anonna, Shamima Nasrin; Shoma, Sharmin Akter; Sattar, Mohammad Mafruhi

2014-01-01

389

Cobra Cytotoxins: Structural Organization and Antibacterial Activity  

PubMed Central

Cardiotoxins (cytotoxins, CT) are ?-structured proteins isolated from the venom of cobra. They consist of 59–61 amino acid residues, whose antiparallel chains form three ‘fingers’. In contrast to neurotoxins with an overall similar fold, CTs are amphiphilic. The amphiphilicity is caused by positively charged lysine and arginine residues flanking the tips of the loops that consist primarily of hydrophobic amino acids. A similar distribution of amino acid residues is typical for linear (without disulfide bonds) cationic cytolytic peptides from the venoms of other snakes and insects. Many of them are now considered to be lead compounds in combatting bacterial infections and cancer. In the present review, we summarize the data on the antibacterial activity of CTs and compare it to the activity of linear peptides. PMID:25349711

Dubovskii, P. V.; Utkin, Y. N.

2014-01-01

390

Antibacterial activity of Aristolochia paucinervis Pomel.  

PubMed

Several fractions of the methanolic extract of the rhizome or the leaves of Aristolochia paucinervis Pomel were screened for antibacterial activity using the agar dilution method against fourteen reference bacterial strains. Only three fractions (defatted chloroformic rhizome fraction: APRC, rhizome ethyl acetate fraction: APRE and leaf chloroform fraction: APLC) showed an activity against at least one of the microorganisms tested. The minimum inhibitory concentration (MIC) determination showed that APRC was the most active against Clostridium perfringens, Clostridium difficile, Enterococcus faecalis, Micrococcus luteus and Bacillus subtilis. The high bacteriostatic activity of APRC was confirmed by its MIC determination against clinical strains of C. perfringens (n = 32), C. difficile (n = 31), and E. faecalis (n = 22). Results of this study suggest the potential interest of this highly active fraction and support the use of A. paucinervis Pomel in Moroccan traditional medicine to treat skin and soft-tissue infections, especially gas gangrene and intestinal diseases. PMID:10616964

Gadhi, C A; Weber, M; Mory, F; Benharref, A; Lion, C; Jana, M; Lozniewski, A

1999-10-01

391

Antibacterial properties of composite UHMWPE/ surfaces  

NASA Astrophysics Data System (ADS)

Due to the diffusion of severe pathogens, everyday life is exposed to the risks of contracting severe diseases. For this reason, efficient antimicrobial surfaces are of paramount importance. In this work we present the first evidences of a new technique to obtain an antibacterial ultra high molecular weight polyethylene based on a non-stoichiometric, visible light responsive, titanium oxide coating. The coating was obtained through a process in which titanium ions, resulting from laser ablation of a corresponding target, were accelerated and implanted on the samples. The samples were tested against a Staphylococcus aureus strain, in order to assay their antimicrobial efficacy. Results show that this treatment strongly discourages bacterial colonization of the treated surfaces.

Delle Side, D.; Nassisi, V.; Giuffreda, E.; Velardi, L.; Alifano, P.; Talà, A.; Tredici, S. M.

2014-10-01

392

Antibacterial activity of some plant extracts used in folk medicine.  

PubMed

In the present work, selected plants were screened for their potential antibacterial activity. For evaluating antibacterial activity, both aqueous and organic solvent methanol was used. The plants screened were Ocimum sanctum, Jatropha gossypifolia, Boerhavia diffusa, Azadirachta indica, Solidago virgaurea, and Commelina benghalensis. The antibacterial activity was assessed against six bacterial strains--Pseudomonas testosteroni, Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus subtilis, Proteus morganii, Micrococcus flavus. Agar disc diffusion method and Agar ditch diffusion method were used to study the antibacterial activity of all these plants. Ps. testosteroni and K. pneumoniae were the most resistant bacterial strains. A. indica showed strong activity against tested bacterial strains. Therefore, we conclude that A. indica may prove to be a promising agent, and further exploration into this compound should be performed to determine its full therapeutic potential. In addition, its leaf extract can also be used as a lead molecule in combating the diseases caused by the studied bacterial strains. PMID:18928141

Nair, Rathish; Kalariya, Tamanna; Chanda, Sumitra

2007-01-01

393

The biology of Mur ligases as an antibacterial target.  

PubMed

With antibiotic resistance mechanisms increasing in diversity and spreading among bacterial pathogens, the development of new classes of antibacterial agents against judiciously chosen targets is a high-priority task. The biochemical pathway for peptidoglycan biosynthesis is one of the best sources of antibacterial targets. Within this pathway are the Mur ligases, described in this review as highly suitable targets for the development of new classes of antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with the same catalytic mechanism and share conserved amino acid regions and structural features that can conceivably be exploited for the design of inhibitors that simultaneously target more than one enzyme. This would provide multi-target antibacterial weapons with minimized likelihood of target-mediated resistance development. PMID:25130693

Kouidmi, Imène; Levesque, Roger C; Paradis-Bleau, Catherine

2014-10-01

394

An antibacterial hydroxy fusidic acid analogue from Acremonium crotocinigenum  

E-print Network

against a panel of multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA reserved. Keywords: Acremonium crotocinigenum; Fusidane triterpene; Fusidic acid; Antibacterial; MRSA; MDR, fusidic acid, a widely used therapeutic for methicillin-resistant Staphylococcus aureus (MRSA) infections

Griffith, Gareth

395

Antibacterial activity of the essential oil from Cymbopogon nervatus inflorescence  

Microsoft Academic Search

Antibacterial activity of essential oil of dried inflorescence of Cymbopogon nervatus was investigated. The essential oil remarkably inhibited the growth of tested bacteria except for Salmonella typhi. The maximum activity was against Shigella dysenteriae and Klebsiella pneumoniae.

H. H. EL-Kamali; M. A. Hamza; M. Y. EL-Amir

2005-01-01

396

informedRx Preferred Drug List -Effective July 1, 2012 Preferred Drug List  

E-print Network

-INFECTIVES (ANTIFUNGALS/ ANTIBIOTICS) ANTIFUNGALS fluconazole, itraconazole, ketoconazole, terbinafine LAMISIL GRANULES, amoxicillin/clavulanate, penicillin vk AUGMENTIN SUSPENSION QUINOLONES ciprofloxacin, ciprofloxacin er

Scharer, John E.

397

Antibacterial activities of fluorovinyl- and chlorovinylglycine and several derived dipeptides.  

PubMed Central

The in vitro antibacterial activities of several halovinylglycine compounds and their L-norvalyl peptide derivatives are presented. The most potent of them, L-norvalyl-L-chlorovinylglycine, displayed good activity against gram-positive organisms, including methicillin-resistant Staphylococcus species. Chlorovinylglycine is an efficient inhibitor of alanine racemase, but the antibacterial activity of L-norvalyl-L-chlorovinylglycine may involve other physiological targets as well. PMID:3284459

Patchett, A A; Taub, D; Weissberger, B; Valiant, M E; Gadebusch, H; Thornberry, N A; Bull, H G

1988-01-01

398

Silver-perfluorodecanethiolate complexes having superhydrophobic, antifouling, antibacterial properties.  

PubMed

Silver-perfluorodecanethiolate complexes having superhydrophobic, antifouling, antibacterial properties were prepared by a reaction of silver nitrate with perfluorodecanethiol. When the silver nitrate to perfluorodecanethiol molar ratio was 1/2, silver-perfluorodecanethiolate complexes having hierarchical micro-/nano-sized wire shapes were obtained, and they showed superhydrophobic and antifouling properties. After UV irradiation, silver nanoparticles were generated on the wires and exhibited antibacterial properties. PMID:22018531

Chung, Jae-Seung; Kim, Byoung Gak; Shim, Soojin; Kim, Seong-Eun; Sohn, Eun-Ho; Yoon, Jeyong; Lee, Jong-Chan

2012-01-15

399

Antibacterial and antifungal activity of Indonesian ethnomedical plants.  

PubMed

Methylene chloride and methanol extracts of 20 Indonesian plants with ethnomedical uses have been assessed for in vitro antibacterial and antifungal properties by disk diffusion method. Extracts of the six plants: Terminalia catappa, Swietenia mahagoni Jacq., Phyllanthus acuminatus, Ipomoea spp., Tylophora asthmatica and Hyptis brevipes demonstrated high activity in this bioassay system. These findings should stimulate the search for novel, natural product such as new antibacterial and antifungal agents. PMID:12946723

Goun, E; Cunningham, G; Chu, D; Nguyen, C; Miles, D

2003-09-01

400

Antibacterial performance of colloidal silver-treated laminate wood flooring  

Microsoft Academic Search

In this study both the anti-bacterial properties and strength of cockroach avoidance of laminate wood floorings containing colloidal silver is evaluated. The laminate wood flooring manufactured with the overlay added with resin containing colloidal silver ion showed an antibacterial activity of up to 98.9%. For colloidal silver-treated, laminate wood flooring, the relative avoidance rate was 87±1%. With colloidal silver treatment

Sumin Kim; Hyun-Joong Kim

2006-01-01

401

The Antibacterial Metabolites and Proacacipetalin from Acacia cochliacantha  

Microsoft Academic Search

Chromatographic purification of the antibacterial hexane, ethyl acetate and methanol extracts from the aerial parts of Acacia cochliacantha provided twelve known antibacterial compounds: b- sitosterol, stigmasterol, b-sitosterol 3-O-b-D-glucoside, stigmasterol 3-O-b-D-glucoside, lupenone, taraxerone, apigenin, luteolin, querce- tin, gallic acid, methyl gallate and salicylic acid whose MIC values were determined. Additionally, proacacipetalin, squalene, (+)-pinitol, and palmitic, linoleic, oleic, stearic and myristic acids

J. Jesús Manríquez-Torres; Armida Zúñiga-Estrada; Manuel González-Ledesma; J. Martín Torres-Valencia

2007-01-01

402

Preparation of nanocomposite fibers for permanent antibacterial effect  

Microsoft Academic Search

The polypropylene\\/silver nanocomposite fibers were prepared for the attainment of permanent antibacterial activity to common synthetic textile. The fibers were melt-spun by co-extrusion of polypropylene (PP) and PP\\/Ag master-batches using general conjugate spinning. Master-batches were made up of mixture of PP chips and nano-sized silver powder. The antibacterial efficacy of spun fibers was excellent not when the master-batch used as

Sang Young Yeo; Hoon Joo Lee; Sung Hoon Jeong

2003-01-01

403

Composition and Antibacterial Activity of Achillea chrysocoma Essential Oil  

Microsoft Academic Search

Essential oil of Achillea chrysocoma Friv. was investigated for composition and antibacterial activity. Twenty-eight identified compounds constituted 91.5% of the oil. The main compounds of the oil were borneol (10.1%), terpinen-4-ol (9.2%), cis-p-menth-2-en-1-ol (8.2%) and trans-p-menth-2-en-1-ol (7.9%). Antibacterial tests showed pronounced activity of the oil against Gram-negative bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa.

Nebojsa Simic; Radosav Palic; Vlatka Vajs; Slobodan Milosavljevic; Dejan Djokovic

2000-01-01

404

Composition and Antibacterial Activity of Achillea asplenifolia Essential Oil  

Microsoft Academic Search

The oil of a wild growing population of Achillea asplenifolia Vent, was studied for yield, composition and antibacterial activity. The major components in the oil were ?-caryophyllene (17.6%), germacrene D (15.6%) and chamazulene (13.3%). In an antibacterial diffusion assay, the oil showed activity against all tested Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) and Gram-positive Staphylococcus aureus.

Nebojsa Simic; Radosav Palic; Vlatka Vajs; Slobodan Milosavljevic; Dejan Djokovic

2002-01-01

405

Antibacterial and antioxidant properties of the methanol extracts of the leaves and stems of Calpurnia aurea  

PubMed Central

Background In South Africa, Calpurnia aurea (Ait.) Benth is used to destroy lice and to relieve itches, to destroy maggots and to treat allergic rashes, particularly those caused by caterpillars. Antioxidants play an important role protecting against damage by reactive oxygen species. Plants containing flavonoids have been reported to possess strong antioxidant properties. Methods The antibacterial, antioxidant activities and phenolic contents of the methanol extracts of the leaves and stems of Calpurnia aurea were evaluated using in vitro standard methods. Spectrophotometry was the basis for the determinations of total phenol, total flavonoids, flavonols, and proanthocyanidins. Tannins, quercetin and catechin equivalents were used for these parameters. The antioxidant activities of the stem extract of Calpurnia aurea were determined by ABTS, DPPH, and ferrous reducing antioxidant property (FRAP) methods. Laboratory isolates of 10 bacteria species which included five Gram-positive and five Gram-negative strains were used to assay for antibacterial activity of this plant. Results The results from this study showed that the antioxidant activities of the stem extract of Calpurnia aurea as determined by the total phenol, flavonoids, and FRAP methods were higher than that of the leaves. On the other hand, the leaf extract of the plant has higher level of total flavonols and proanthocyanidins. The leaf extract also has higher radical scavenging activity as shown in 1, 1-Diphenyl-2-picrylhydrazyl (DPPH), and 2,2¿-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) assay. The leaf extract showed activity against seven of the bacterial organisms. Conclusion The results from this study indicate that the leaves and stem extracts of Calpurnia aurea possess antioxidant properties and could serve as free radical inhibitors or scavenger or, acting possibly as primary antioxidants. Although, the antibacterial properties of Calpurnia aurea are not as effective as the standard drugs- Chloramphenicol and Streptomycin, they still possess some activity against bacterial strains used in this study. Calpurnia aurea may therefore be a good candidate for functional foods as well as pharmaceutical plant-based products. PMID:18803865

Adedapo, Adeolu A; Jimoh, Florence O; Koduru, Srinivas; Afolayan, Anthony J; Masika, Patrick J

2008-01-01

406

Antibacterial substances from marine algae isolated from Jeddah coast of Red sea, Saudi Arabia.  

PubMed

Marine algae are known to produce a wide variety of bioactive secondary metabolites and several compounds have been derived from them for prospective development of novel