Inhibition of human immunodeficiency virus by a new class of pyridine oxide derivatives.

Abstract:

:A new class of pyridine oxide derivatives as inhibitors of human immunodeficiency virus type 1 (HIV-1) and/or HIV-2 replication in cell culture has been identified. The compounds, which specifically inhibit HIV-1, behave as typical nonnucleoside reverse transcriptase inhibitors (NNRTIs). The most active congener of this group, JPL-133 (UC-B3096), has a 50% effective concentration of 0.05 microg/ml for HIV-1(III(B)) with a selectivity index of approximately 760 in CEM cell cultures. However, the cytostatic activity of most pyridine oxide derivatives highly depended on the nature of the cell line. All compounds, including those pyridine oxide derivatives that inhibit both HIV-1 and HIV-2 replication, select for NNRTI-characteristic mutations in the HIV-1 reverse transcriptase of HIV-infected cell cultures (i.e., Lys103Asn, Val108Ile, Glu138Lys, Tyr181Cys and Tyr188His). These amino acid mutations emerged mostly through transition of guanine to adenine or adenine to guanine in the corresponding codons of the reverse transcriptase (RT) gene. The HIV-1-specific pyridine oxide derivatives lost their antiviral activity against HIV-1 strains containing these mutations in the RT. However, most compounds retained pronounced antiviral potency against virus strains that contained other NNRTI-characteristic RT mutations, such as Leu100Ile and Val179Asp. Furthermore, the complete lack of inhibitory activity of the pyridine oxide derivatives against recombinant HIV-2 RT and partial retention of anti-HIV-1 activity against HIV-1 strains that contain a variety of HIV-1-characteristic mutations suggest that the pyridine oxide derivatives must have a second target of antiviral action independent from HIV-1 RT.

authors

Stevens M,Pannecouque C,De Clercq E,Balzarini J

doi

10.1128/aac.47.9.2951-2957.2003

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

2951-7

issue

9

eissn

0066-4804

issn

1098-6596

journal_volume

47

pub_type

杂志文章
  • Clinical isolates of Staphylococcus aureus with ribosomal mutations conferring resistance to macrolides.

    abstract::Six strains of Staphylococcus aureus isolated from cystic fibrosis patients after treatment with azithromycin were cross-resistant to azithromycin and erythromycin. None of the isolates contained erm or msr(A) genes, but they all carried either A2058G/U or A2059G mutations within the rrl genes, with a majority of the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.9.3054-3056.2002

    authors: Prunier AL,Malbruny B,Tandé D,Picard B,Leclercq R

    更新日期:2002-09-01 00:00:00

  • Hypermutator Pseudomonas aeruginosa Exploits Multiple Genetic Pathways To Develop Multidrug Resistance during Long-Term Infections in the Airways of Cystic Fibrosis Patients.

    abstract::Pseudomonas aeruginosa exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in P. aeruginosa isolates recovered from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic infec...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02142-19

    authors: Colque CA,Albarracín Orio AG,Feliziani S,Marvig RL,Tobares AR,Johansen HK,Molin S,Smania AM

    更新日期:2020-04-21 00:00:00

  • Activity of cefepime against ceftazidime- and cefotaxime-resistant gram-negative bacteria and its relationship to beta-lactamase levels.

    abstract::One hundred clinical isolates resistant to ceftazidime and/or cefotaxime were examined for susceptibility to cefepime. The most frequently encountered ceftazidime-cefotaxime-resistant strains belonged to the genera Enterobacter, Pseudomonas, and Citrobacter. Among these strains, 92% were resistant to cefoperazone, 91%...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.4.498

    authors: Fung-Tomc J,Dougherty TJ,DeOrio FJ,Simich-Jacobson V,Kessler RE

    更新日期:1989-04-01 00:00:00

  • Therapeutic efficacy of liposomal rifabutin in a Mycobacterium avium model of infection.

    abstract::Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of inf...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.9.2424-2430.2000

    authors: Gaspar MM,Neves S,Portaels F,Pedrosa J,Silva MT,Cruz ME

    更新日期:2000-09-01 00:00:00

  • Local treatment of experimental Pseudomonas aeruginosa osteomyelitis with a biodegradable dilactide polymer releasing ciprofloxacin.

    abstract::A biodegradable system of poly-D,L-dilactide releasing ciprofloxacin was assessed in a Pseudomonas aeruginosa osteomyelitis model after inoculation of the test pathogen into the left tibia of 76 New Zealand White rabbits; 31 were controls (group A), and 45 were implanted with the polymer at the infection site (group B...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01360-07

    authors: Kanellakopoulou K,Thivaios GC,Kolia M,Dontas I,Nakopoulou L,Dounis E,Giamarellos-Bourboulis EJ,Andreopoulos A,Karagiannakos P,Giamarellou H

    更新日期:2008-07-01 00:00:00

  • The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection.

    abstract::Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. How...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02761-16

    authors: Kasetty G,Bhongir RKV,Papareddy P,Herwald H,Egesten A

    更新日期:2017-08-24 00:00:00

  • Mutations in a 23S rRNA gene of Chlamydia trachomatis associated with resistance to macrolides.

    abstract::For six clinical isolates of Chlamydia trachomatis, in vitro susceptibility to erythromycin, azithromycin, and josamycin has been determined. Four isolates were resistant to all the antibiotics and had the mutations A2058C and T2611C (Escherichia coli numbering) in the 23S rRNA gene. All the isolates had mixed populat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.48.4.1347-1349.2004

    authors: Misyurina OY,Chipitsyna EV,Finashutina YP,Lazarev VN,Akopian TA,Savicheva AM,Govorun VM

    更新日期:2004-04-01 00:00:00

  • In vitro antimicrobial susceptibility of bacterial enteropathogens isolated from international travelers to Mexico, Guatemala, and India from 2006 to 2008.

    abstract::The incidence rates of travelers' diarrhea (TD) have remained high for the last 50 years. More recently, there have been increasing recommendations for self-initiated therapy and use of prophylactic drugs for TD. We last examined the in vitro susceptibilities of commonly used antibiotics against TD pathogens in 1997. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00739-10

    authors: Ouyang-Latimer J,Jafri S,VanTassel A,Jiang ZD,Gurleen K,Rodriguez S,Nandy RK,Ramamurthy T,Chatterjee S,McKenzie R,Steffen R,DuPont HL

    更新日期:2011-02-01 00:00:00

  • Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs.

    abstract::Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates aga...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00819-20

    authors: Jeon S,Ko M,Lee J,Choi I,Byun SY,Park S,Shum D,Kim S

    更新日期:2020-06-23 00:00:00

  • Stepwise upregulation of the Pseudomonas aeruginosa chromosomal cephalosporinase conferring high-level beta-lactam resistance involves three AmpD homologues.

    abstract::Development of resistance to the antipseudomonal penicillins and cephalosporins mediated by hyperproduction of the chromosomal cephalosporinase AmpC is a major threat to the successful treatment of Pseudomonas aeruginosa infections. Although ampD inactivation has been previously found to lead to a partially derepresse...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.5.1780-1787.2006

    authors: Juan C,Moyá B,Pérez JL,Oliver A

    更新日期:2006-05-01 00:00:00

  • In vitro activity of Bay v 3522, a new cephalosporin, compared with activities of other agents.

    abstract::The in vitro activity of Bay v 3522, a new aminobenzothiazol cephem, was compared with those of other oral beta-lactams. Bay v 3522 displayed high activity against Staphylococcus spp. (MICs for 90% of strains tested [MIC90S], 0.5 micrograms/ml), Streptococcus pneumoniae (MIC90, 0.06 micrograms/ml), and Haemophilus inf...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.5.813

    authors: Wise R,Andrews JM,Ashby JP,Thornber D

    更新日期:1990-05-01 00:00:00

  • WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015.

    abstract::WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00072-17

    authors: Sader HS,Castanheira M,Huband M,Jones RN,Flamm RK

    更新日期:2017-04-24 00:00:00

  • Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection.

    abstract::Limited antiretrovirals are currently available for the management of multidrug-resistant (MDR) HIV-1 infection. Ibalizumab, a recombinant humanized monoclonal antibody, represents the first novel agent for HIV-1 management in over a decade and is the first monoclonal antibody for the treatment of MDR HIV-1 infection ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,评审

    doi:10.1128/AAC.00110-19

    authors: Beccari MV,Mogle BT,Sidman EF,Mastro KA,Asiago-Reddy E,Kufel WD

    更新日期:2019-05-24 00:00:00

  • 9-[2-(Phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques.

    abstract::The long-term therapeutic and toxic effects of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) were evaluated in simian immunodeficiency virus (SIV)-infected newborn rhesus macaques. Four untreated SIV-infected newborn macaques developed persistently high levels of viremia, and three of the four animals had rapidly fatal...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.11.2586

    authors: Van Rompay KK,Cherrington JM,Marthas ML,Berardi CJ,Mulato AS,Spinner A,Tarara RP,Canfield DR,Telm S,Bischofberger N,Pedersen NC

    更新日期:1996-11-01 00:00:00

  • Tilorone hydrochloride: an oral interferon-inducing agent.

    abstract::Tilorone hydrochloride characteristically induces an unusually delayed and prolonged interferon response not commonly associated with other synthetic inducers. Maximum circulating interferon levels of 8,000 to 10,000 units/ml were detected 12 hr postinoculation and persisted for up to 30 hr after administration of til...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.2.2.73

    authors: Stringfellow DA,Glasgow LA

    更新日期:1972-08-01 00:00:00

  • Detection of a new SHV-type extended-spectrum beta-lactamase, SHV-31, in a Klebsiella pneumoniae strain causing a large nosocomial outbreak in The Netherlands.

    abstract::A Klebsiella pneumoniae strain resistant to third-generation cephalosporins was isolated in the eastern Netherlands. The strain was found to carry a novel extended-spectrum beta-lactamase, namely, SHV-31. The combination of the two mutations by which SHV-31 differs from SHV-1, namely, L35Q and E240K, had previously on...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00909-06

    authors: Mazzariol A,Roelofsen E,Koncan R,Voss A,Cornaglia G

    更新日期:2007-03-01 00:00:00

  • Biogenesis of the mycobacterial cell wall and the site of action of ethambutol.

    abstract::The effect of ethambutol (EMB) is primarily on polymerization steps in the biosynthesis of the arabinan component of cell wall arabinogalactan (AG) of Mycobacterium smegmatis. Inhibition of the synthesis of the arabinan of lipoarabinomannan (LAM) occurred later, and thus in the cases of AG and LAM, the polymerization ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.11.2484

    authors: Mikusová K,Slayden RA,Besra GS,Brennan PJ

    更新日期:1995-11-01 00:00:00

  • Pharmacokinetics of Penicillin G in Preterm and Term Neonates.

    abstract::Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but have been poorly described for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We describe th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02238-17

    authors: Padari H,Metsvaht T,Germovsek E,Barker CI,Kipper K,Herodes K,Standing JF,Oselin K,Tasa T,Soeorg H,Lutsar I

    更新日期:2018-04-26 00:00:00

  • Clinical Mutations That Partially Activate the Stringent Response Confer Multidrug Tolerance in Staphylococcus aureus.

    abstract::Antibiotic tolerance is an underappreciated antibiotic escape strategy that is associated with recurrent and relapsing infections, as well as acting as a precursor to resistance. Tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic w...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02103-19

    authors: Bryson D,Hettle AG,Boraston AB,Hobbs JK

    更新日期:2020-02-21 00:00:00

  • Mutation in enterovirus 71 capsid protein VP1 confers resistance to the inhibitory effects of pyridyl imidazolidinone.

    abstract::Enterovirus 71 is one of the most important pathogens in the family of Picornaviridae that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor. Pyridyl imidazolid...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.9.3523-3529.2004

    authors: Shih SR,Tsai MC,Tseng SN,Won KF,Shia KS,Li WT,Chern JH,Chen GW,Lee CC,Lee YC,Peng KC,Chao YS

    更新日期:2004-09-01 00:00:00

  • Classification of R plasmids by incompatibility in Pseudomonas aeruginosa.

    abstract::R plasmids identified in Pseudomonas aeruginosa strains isolated in our laboratories were classified by their incompatibility characters by using intraspecies conjugation in P. aeruginosa. The fertility factor, FP2, was compatible with R plasmids belonging to all groups, and was classified in a new group. From these d...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.10.4.573

    authors: Sagai H,Hasuda K,Iyobe S,Bryan LE,Holloway BW,Mitsuhashi S

    更新日期:1976-10-01 00:00:00

  • Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination.

    abstract::Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrati...

    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.33.3.356

    authors: Ko H,Cathcart KS,Griffith DL,Peters GR,Adams WJ

    更新日期:1989-03-01 00:00:00

  • Tolerance of Haemophilus influenzae to beta-lactam antibiotics.

    abstract::Two hundred clinical isolates of Haemophilus influenzae were tested for tolerance (MBC/MIC greater than or equal to 32) to ampicillin and cefotaxime by broth dilution tests. Of 200 strains, 9 were tolerant to ampicillin, and 10 were tolerant to cefotaxime. Tolerant organisms were identified in both systemic and nonsys...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.28.2.320

    authors: Bergeron MG,Lavoie GY

    更新日期:1985-08-01 00:00:00

  • Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy.

    abstract::There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have no...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01763-16

    authors: Sime FB,Johnson A,Whalley S,Santoyo-Castelazo A,Montgomery AB,Walters KA,Lipman J,Hope WW,Roberts JA

    更新日期:2016-12-27 00:00:00

  • Efficacy of pyrvinium pamoate against Cryptosporidium parvum infection in vitro and in a neonatal mouse model.

    abstract::No effective approved drug therapy exists for Cryptosporidium infection of immunocompromised patients. Here we investigated the nonabsorbed anthelmintic drug pyrvinium pamoate for inhibition of the growth of the intestinal protozoan parasite Cryptosporidium parvum. The concentration of pyrvinium that effected 50% grow...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00207-08

    authors: Downey AS,Chong CR,Graczyk TK,Sullivan DJ

    更新日期:2008-09-01 00:00:00

  • Anti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives.

    abstract::Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of current combination therapies for human immunodeficiency virus type 1 (HIV-1) infection. In screening of chemical libraries, we found 6-azido-1-benzyl-3-(3,5-dimethylbenzyl)uracil (AzBBU) and 6-amino-1-benzyl-3-(3,5-dimethylbenzyl...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.06307-11

    authors: Ordonez P,Hamasaki T,Isono Y,Sakakibara N,Ikejiri M,Maruyama T,Baba M

    更新日期:2012-05-01 00:00:00

  • Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10.

    abstract::Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the compon...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.2.480-489.2006

    authors: Afonso A,Hunt P,Cheesman S,Alves AC,Cunha CV,do Rosário V,Cravo P

    更新日期:2006-02-01 00:00:00

  • Proof-of-Principle Study in a Murine Lung Infection Model of Antipseudomonal Activity of Phage PEV20 in a Dry-Powder Formulation.

    abstract::Bacteriophage therapy is a promising alternative treatment to antibiotics, as it has been documented to be efficacious against multidrug-resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery; however, p...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01714-17

    authors: Chang RYK,Chen K,Wang J,Wallin M,Britton W,Morales S,Kutter E,Li J,Chan HK

    更新日期:2018-01-25 00:00:00

  • Rifampin: inhibition of ribonucleic acid synthesis after potentiation by amphotericin B in Saccharomyces cerevisiae.

    abstract::The inhibition of Saccharomyces cerevisiae growth by amphotericin B and rifampin was studied. Rifampin alone had no effect on growth or macromolecular syntheses. Lethal amounts of amphotericin B produced a late inhibition of ribonucleic acid (RNA) synthesis simultaneous with the arrest of growth and protein synthesis....

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.5.4.371

    authors: Battaner E,Kumar BV

    更新日期:1974-04-01 00:00:00

  • Genomic Characterization of VIM Metallo-β-Lactamase-Producing Alcaligenes faecalis from Gaza, Palestine.

    abstract::Carbapenemase-producing Gram-negative bacteria (CP-GNB) have increasingly spread worldwide, and different families of carbapenemases have been identified in various bacterial species. Here, we report the identification of five VIM metallo-β-lactamase-producing Alcaligenes faecalis isolates associated with a small outb...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01499-17

    authors: Al Laham N,Chavda KD,Cienfuegos-Gallet AV,Kreiswirth BN,Chen L

    更新日期:2017-10-24 00:00:00