Abstract:
:Recent years have seen the rapid advancement of new therapeutic agents against hepatitis C virus (HCV) in response to the need for treatment that is unmet by interferon (IFN)-based therapies. Most antiviral drugs discovered to date are small molecules that modulate viral enzyme activities. In the search for highly selective protein-binding molecules capable of disrupting the viral life cycle, we have identified a class of anionic tetraphenylporphyrins as potent and specific inhibitors of the HCV replicons. Based on the structure-activity relationship studies reported herein, meso-tetrakis-(3,5-dicarboxy-4,4'-biphenyl) porphyrin was found to be the most potent inhibitor of HCV genotype 1b (Con1) replicon systems but was less effective against the genotype 2a (JFH-1) replicon. This compound induced a reduction of viral RNA and protein levels when acting in the low nanomolar range. Moreover, the compound could suppress replicon rebound in drug-treated cells and exhibited additive to synergistic effects when combined with protease inhibitor BILN 2061 or with IFN-alpha-2a. Our results demonstrate the potential use of tetracarboxyphenylporphyrins as potent anti-HCV agents.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Cheng Y,Tsou LK,Cai J,Aya T,Dutschman GE,Gullen EA,Grill SP,Chen AP,Lindenbach BD,Hamilton AD,Cheng YCdoi
10.1128/AAC.01206-09subject
Has Abstractpub_date
2010-01-01 00:00:00pages
197-206issue
1eissn
0066-4804issn
1098-6596pii
AAC.01206-09journal_volume
54pub_type
杂志文章abstract::SCE-129 [3-(4-carbamoyl-1-pyridiniomethyl)-7beta-(d-alpha-sulfophenylacetamido)-ceph-3-em-4-carboxylate monosodium salt], a new semisynthetic cephalosporin, shows potent in vitro antibacterial activities against Pseudomonas aeruginosa and some gram-positive bacteria, whereas it shows lower activity against many gram-n...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.2.137
更新日期:1978-02-01 00:00:00
abstract::Cystathionine gamma-lyase (EC 4.4.1.1) was purified from Streptomyces cattleya, an actinomycete which produces the unusual beta-lactam antibiotic thienamycin. The enzyme displays broad substrate specificity and is similar to gamma-lyases purified from other microorganisms. That the gamma-lyase functions in vivo to pro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.4.478
更新日期:1985-10-01 00:00:00
abstract::We performed the characterization of a multidrug-resistant (MDR) Enterobacter spp. isolate highlighting the genetic aspects of the antimicrobial resistance genes. An Enterobacter spp. isolate (Ec61) was recovered in 2014 from a transtracheal aspirate sample from a patient admitted to a Brazilian tertiary hospital and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01193-20
更新日期:2020-12-14 00:00:00
abstract::The antimicrobial efflux system encoded by the operon mef(E)-mel on the mobile genetic element MEGA in Streptococcus pneumoniae and other Gram-positive bacteria is inducible by macrolide antibiotics and antimicrobial peptides. Induction may affect the clinical response to the use of macrolides. We developed mef(E) rep...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00060-11
更新日期:2011-07-01 00:00:00
abstract::We investigated the impact of the piperacillin-tazobactam MIC in the outcome of 39 bloodstream infections due to extended-spectrum-β-lactamase-producing Escherichia coli. All 11 patients with urinary tract infections survived, irrespective of the MIC. For other sources, 30-day mortality was lower for isolates with a M...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00135-13
更新日期:2013-07-01 00:00:00
abstract::The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces dermatitidis (MIC = 0.048 microgram/ml; minimal fungicidal concentration = 0.097 microgram/ml). In vivo, D0870 was appro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.5.1177
更新日期:1993-05-01 00:00:00
abstract::The emergence of resistance to last-resort antibiotics is a public health concern of global scale. Besides direct person-to-person propagation, environmental pathways might contribute to the dissemination of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Here, we describe the incidence of blaNDM...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00236-16
更新日期:2016-08-22 00:00:00
abstract::Our aim was to assess the effect of miconazole oral gel on the pharmacokinetics of oral oxycodone. In an open crossover study with two phases, 12 healthy volunteers took a single oral dose of 10 mg of immediate-release oxycodone with or without thrice-daily 85-mg miconazole oral gel treatment. The plasma concentration...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01242-10
更新日期:2011-03-01 00:00:00
abstract::Although fluoroquinolone antibiotics such as ciprofloxacin are able to gain access to lung tissue and both pleural and bronchial secretions, the characteristics of transport and cellular uptake of ciprofloxacin in human epithelial lung tissue remain obscure. We have chosen human airway epithelial (Calu-3) cells, recon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.12.2693
更新日期:1997-12-01 00:00:00
abstract::Salmonella typhimurium isolated in Bombay from fecal samples of 145 patients suffering from gastroenteritis (group 1) and from the cerebrospinal fluid, feces, or blood of 42 patients with systemic salmonellosis (group 2) were examined for the antimicrobial resistance and incompatibility groups of their R plasmids. Mul...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.1.54
更新日期:1983-01-01 00:00:00
abstract::The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were evaluated over 24 to 48 h against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA 1199 and MRSA 494, respectively)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.12.2702
更新日期:1994-12-01 00:00:00
abstract::Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblas...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02325-18
更新日期:2019-03-27 00:00:00
abstract::The activities of niridazole and metronidazole were compared by an agar dilution method against 40 strains of Campylobacter fetus subsp. jejuni of human origin. Niridazole had a markedly higher activity than metronidazole. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.1.145
更新日期:1984-01-01 00:00:00
abstract::Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.298
更新日期:1981-09-01 00:00:00
abstract::The multiple-dose pharmacokinetics of amoxicillin (AM [administered twice daily in a 25-mg/kg of body weight intravenous dose]) in 17 preterm infants (11 males; gestational age, 29 +/- 1.9 weeks; birth weight, 1,175 +/- 278 g) were evaluated on day 3 of life. Blood samples were collected from an arterial catheter at 0...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.2.431
更新日期:1995-02-01 00:00:00
abstract::We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P. carinii, causing irreversible damage, thus indi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3560-3565.2001
更新日期:2001-12-01 00:00:00
abstract::Since human cytomegalovirus (HCMV) does not infect or replicate in nonhuman cells and tissues, there are few animal models currently available for evaluation of antiviral therapies for these infections. In the present studies, we utilized two different models in which severe combined immunodeficient (SCID) mice were i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.5.1749-1755.2004
更新日期:2004-05-01 00:00:00
abstract::This paper reports an evaluation of a melamino nitroheterocycle, a potential lead for further development as an agent against human African trypanosomiasis (HAT). Studies on its efficacy, physicochemical and biopharmaceutical properties, and potential for toxicity are described. The compound previously had been shown ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01449-13
更新日期:2014-10-01 00:00:00
abstract::Indwelling device infections are associated with considerable morbidity and extremely high cost. Pseudomonas aeruginosa is the most frequent gram-negative etiologic agent associated with infections of indwelling catheters and foreign body implants. It is generally agreed that eradication of infection in the presence o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.39.11.2423
更新日期:1995-11-01 00:00:00
abstract::Streptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which can be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococcus-specific lysin ClyJ comprising the binding doma...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00311-20
更新日期:2020-11-17 00:00:00
abstract::9-[2-(Boranophosphonomethoxy)ethyl]adenine diphosphate (BH(3)-PMEApp) and (R)-9-[2-(boranophosphonomethoxy)propyl]adenine diphosphate (BH(3)-PMPApp), described here, represent the first nucleoside phosphonates modified on their alpha-phosphates that act as efficient substrates for the human immunodeficiency virus type...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00145-07
更新日期:2007-09-01 00:00:00
abstract::Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited setting...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00439-16
更新日期:2016-09-23 00:00:00
abstract::Respiratory syncytial virus (RSV) causes serious illness (lower respiratory illness) in preterm infants. RSV antibody-enriched immunoglobulin (RSVIG) that was lyophilized (LYO) protected against RSV lower respiratory illness. The Food and Drug Administration now requires an additional viral inactivation step (VI). We ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.39.3.668
更新日期:1995-03-01 00:00:00
abstract::Alalevonadifloxacin (WCK 2349) is a novel l-alanine ester prodrug of levonadifloxacin that is being developed as an oral fluoroquinolone antibiotic. The primary objective of this study was to determine and compare plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levonadifloxacin fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02297-17
更新日期:2018-02-23 00:00:00
abstract::Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carryi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02369-16
更新日期:2017-02-23 00:00:00
abstract::Mycobacterium leprae synthesizes large quantities of a specific phthiocerol-containing phenolic glycolipid in vivo. We have shown earlier that viable M. leprae readily incorporates radiolabeled palmitic acid into phenolic glycolipid I when residing in cultured macrophages in vitro and that this process is inhibited by...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.5.657
更新日期:1989-05-01 00:00:00
abstract::Serum and milk concentrations of rifamycin SV and rifampin were determined in lactating ewes after a single intravenous injection, and pharmacokinetic parameters were evaluated by the two-compartment open-system model. Rifampin was distributed throughout a greater volume than rifamycin SV and was eliminated more slowl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.2.139
更新日期:1974-02-01 00:00:00
abstract::The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.6.1403
更新日期:1997-06-01 00:00:00
abstract::The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, (Z)-1-[N-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.9.2342
更新日期:1998-09-01 00:00:00
abstract::The antibacterial drug nalidixic acid (Nal) can suppress the growth of Candida albicans at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temper...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.3.485
更新日期:1976-03-01 00:00:00