Antimalarial activities and therapeutic properties of febrifugine analogs.

Abstract:

:Febrifugine is the active principal isolated 50 years ago from the Chinese herb chang shan (Dichroa febrifuga Lour), which has been used as an antimalarial in Chinese traditional medicine for more than 2,000 years. However, intensive study of the properties of febrifugine has been hindered for decades due to its side effects. We report new findings on the effects of febrifugine analogs compared with those of febrifugine extracted from the dry roots of D. febrifuga. The properties of the extracted febrifugine were comparable to those obtained from the standard febrifugine provided by our collaborators. A febrifugine structure-based computer search of the Walter Reed Chemical Information System identified 10 analogs that inhibited parasite growth in vitro, with 50% inhibitory concentrations ranging from 0.141 to 290 ng/ml. The host macrophages (J744 cells) were 50 to 100 times less sensitive to the febrifugine analogs than the parasites. Neuronal (NG108) cells were even more insensitive to these drugs (selectivity indices, >1,000), indicating that a feasible therapeutic index for humans could be established. The analogs, particularly halofuginone, notably reduced parasitemias to undetectable levels and displayed curative effects in Plasmodium berghei-infected mice. Recrudescence of the parasites after treatment with the febrifugine analogs was the key factor that caused the death of most of the mice in groups receiving an effective dose. Subcutaneous treatments with the analogs did not cause irritation of the gastrointestinal tract when the animals were treated with doses within the antimalarial dose range. In summary, these analogs appear to be promising lead antimalarial compounds that require intensive study for optimization for further down-selection and development.

authors

Jiang S,Zeng Q,Gettayacamin M,Tungtaeng A,Wannaying S,Lim A,Hansukjariya P,Okunji CO,Zhu S,Fang D

doi

10.1128/AAC.49.3.1169-1176.2005

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

1169-76

issue

3

eissn

0066-4804

issn

1098-6596

pii

49/3/1169

journal_volume

49

pub_type

杂志文章
  • Characterization of a Mycobacterium smegmatis mutant lacking penicillin binding protein 1.

    abstract::The ponA gene of Mycobacterium smegmatis encodes a 95-kDa penicillin binding protein, PBP1, that is similar to PBP1s of Mycobacterium tuberculosis and Mycobacterium leprae. Transposon disruption of ponA in M. smegmatis resulted in a PBP1-deficient mutant that was sensitive to beta-lactam antibiotics, was more permeabl...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.12.3011

    authors: Billman-Jacobe H,Haites RE,Coppel RL

    更新日期:1999-12-01 00:00:00

  • Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients.

    abstract::The aim of this study was to investigate the variability of the voriconazole plasma level and its relationships with clinical outcomes and adverse events among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included, and vo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01211-17

    authors: Hashemizadeh Z,Badiee P,Malekhoseini SA,Raeisi Shahraki H,Geramizadeh B,Montaseri H

    更新日期:2017-11-22 00:00:00

  • Effect of N, N'-dicyclohexylcarbodiimide and nigericin on Staphylococcus aureus susceptibility to gentamicin.

    abstract::The abilities of the H+-ATPase inhibitor N, N'-dicyclohexylcarbodiimide and the antibiotic ionophore nigericin to enhance the bactericidal effect of subinhibitory concentrations of gentamicin in two strains of Staphylococcus aureus were studied. Each compound significantly increased both gentamicin uptake and killing....

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.24.3.440

    authors: Mandel LJ,Eisenberg ES,Simkin NJ,Miller MH

    更新日期:1983-09-01 00:00:00

  • Deciphering tuberactinomycin biosynthesis: isolation, sequencing, and annotation of the viomycin biosynthetic gene cluster.

    abstract::The tuberactinomycin antibiotics are essential components in the drug arsenal against Mycobacterium tuberculosis infections and are specifically used for the treatment of multidrug-resistant tuberculosis. These antibiotics are also being investigated for their targeting of the catalytic RNAs involved in viral replicat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.9.2823-2830.2003

    authors: Thomas MG,Chan YA,Ozanick SG

    更新日期:2003-09-01 00:00:00

  • Class 1 integron-borne multiple-antibiotic resistance carried by IncFI and IncL/M plasmids in Salmonella enterica serotype typhimurium.

    abstract::The presence and genetic content of integrons were investigated for 37 epidemiologically unrelated multiple-drug-resistant strains of Salmonella enterica serotype Typhimurium from humans. All isolates were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, sulfonamides, and trimethoprim, as well as to ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.42.12.3053

    authors: Tosini F,Visca P,Luzzi I,Dionisi AM,Pezzella C,Petrucca A,Carattoli A

    更新日期:1998-12-01 00:00:00

  • Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia.

    abstract::Low-level vancomycin-resistant Staphylococcus aureus (vancomycin-intermediate S. aureus [VISA] and heterogenous VISA [hVISA]) is increasingly reported and leads to glycopeptide treatment failure. Various phenotypic features have been reported for these isolates, but the genetic changes leading to hVISA and VISA have y...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00422-06

    authors: Howden BP,Johnson PD,Ward PB,Stinear TP,Davies JK

    更新日期:2006-09-01 00:00:00

  • Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary infections.

    abstract::The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01596-13

    authors: Henry M,Lavigne R,Debarbieux L

    更新日期:2013-12-01 00:00:00

  • In vitro activity of garenoxacin against Streptococcus pneumoniae mutants with characterized resistance mechanisms.

    abstract::We evaluated the potency of garenoxacin in selecting resistant Streptococcus pneumoniae mutants by determining its mutant prevention concentration, using strains with and without topoisomerase gene mutations, and compared its potency to that of other quinolones. Garenoxacin had a significantly greater potency against ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00176-09

    authors: Yamamoto K,Yanagihara K,Sugahara K,Imamura Y,Seki M,Izumikawa K,Kakeya H,Yamamoto Y,Hirakata Y,Kamihira S,Kohno S

    更新日期:2009-08-01 00:00:00

  • Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV.

    abstract::Quinazoline-2,4-diones, such as PD 0305970, are new DNA gyrase and topoisomerase IV (topo IV) inhibitors with potent activity against gram-positive pathogens, including quinolone-resistant isolates. The mechanistic basis of dione activity vis-à-vis quinolones is not understood. We present evidence for Streptococcus pn...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00113-09

    authors: Pan XS,Gould KA,Fisher LM

    更新日期:2009-09-01 00:00:00

  • Structure-function relationship studies on the frog skin antimicrobial peptide tigerinin 1: design of analogs with improved activity and their action on clinical bacterial isolates.

    abstract::Structure-function relationships in antimicrobial peptides have been extensively investigated in order to obtain improved analogs. Most of these studies have targeted either alpha-helical peptides or beta-sheet peptides with multiple disulfide bridges. Tigerinins are short, nonhelical antimicrobial peptides with a sin...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.7.2279-2283.2002

    authors: Sitaram N,Sai KP,Singh S,Sankaran K,Nagaraj R

    更新日期:2002-07-01 00:00:00

  • Sodium hexametaphosphate sensitizes Pseudomonas aeruginosa, several other species of Pseudomonas, and Escherichia coli to hydrophobic drugs.

    abstract::Many gram-negative bacteria are known to be remarkably resistant to hydrophobic noxious agents by virtue of their outer membranes (OM). We investigated, by using four different assay methods, the ability of sodium hexametaphosphate (HMP) to disrupt this OM barrier. (i) In the growth inhibition assay, HMP was found to ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.10.1741

    authors: Vaara M,Jaakkola J

    更新日期:1989-10-01 00:00:00

  • In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium.

    abstract::Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01465-12

    authors: Paredes A,de Campos Lourenço T,Marzal M,Rivera A,Dorny P,Mahanty S,Guerra-Giraldez C,García HH,Nash TE,Cass QB,Cysticercosis Working Group in Peru.

    更新日期:2013-02-01 00:00:00

  • Chromosome-encoded extended-spectrum class A β-lactamase MIN-1 from Minibacterium massiliensis.

    abstract::Minibacterium massiliensis strain CIP107820 is a recently discovered waterborne Gram-negative rod isolated from hospital water samples. It harbors a chromosomally located gene encoding an Ambler class A extended-spectrum β-lactamase termed MIN-1, sharing 56%, 54%, and 51% amino acid identities with β-lactamases LUT-1,...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.06401-11

    authors: Bercot B,Nordmann P,Drancourt M,Poirel L

    更新日期:2012-07-01 00:00:00

  • Submicellar complexes may initiate the fungicidal effects of cationic amphiphilic compounds on Candida albicans.

    abstract::The killing of Candida albicans by a series of amphiphilic quaternary ammonium compounds (QACs) with different hydrocarbon chain lengths was closely related to the binding of the compounds to the cells and damage of the cell membranes. The membrane damage was measured as the level of release of the UV-absorbing materi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.3.544

    authors: Ahlström B,Chelminska-Bertilsson M,Thompson RA,Edebo L

    更新日期:1997-03-01 00:00:00

  • Role of PBPD1 in stimulation of Listeria monocytogenes biofilm formation by subminimal inhibitory β-lactam concentrations.

    abstract::Disinfectant-tolerant Listeria monocytogenes biofilms can colonize surfaces that come into contact with food, leading to contamination and, potentially, food-borne illnesses. To better understand the process of L. monocytogenes biofilm formation and dispersal, we screened 1,120 off-patent FDA-approved drugs and identi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03671-14

    authors: Nguyen UT,Harvey H,Hogan AJ,Afonso AC,Wright GD,Burrows LL

    更新日期:2014-11-01 00:00:00

  • Nonnucleoside inhibitors of norovirus RNA polymerase: scaffolds for rational drug design.

    abstract::Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02799-13

    authors: Eltahla AA,Lim KL,Eden JS,Kelly AG,Mackenzie JM,White PA

    更新日期:2014-06-01 00:00:00

  • Rifampin susceptibility of ribonucleic acid synthesis in a fragile Saccharomyces cerevisiae mutant.

    abstract::Ribonucleic acid (RNA) synthesis in the sorbitol-dependent, fragile yeast mutant VY1160 (Venkov et al., 1974) is rapidly inhibited by rifampin. The growth of the mutant cells and protein synthesis are more slowly affected by the antibiotic, apparently as secondary phenomena. Lower doses of rifampin (50 to 100 mug/ml) ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.8.6.627

    authors: Venkov PV,Milchev GI,Hadjiolov AA

    更新日期:1975-12-01 00:00:00

  • Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers.

    abstract::In an open, randomized, six-period crossover study, the pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were compared after a single oral dose in 12 healthy volunteers (6 men and 6 women). The volunteers received 250 mg of ciprofloxacin, 400 mg of gatifloxa...

    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.44.10.2600-2603.2000

    authors: Lubasch A,Keller I,Borner K,Koeppe P,Lode H

    更新日期:2000-10-01 00:00:00

  • Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection.

    abstract::Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patient...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.03246-14

    authors: Svensson EM,Dooley KE,Karlsson MO

    更新日期:2014-11-01 00:00:00

  • Bioluminescence and 19F magnetic resonance imaging visualize the efficacy of lysostaphin alone and in combination with oxacillin against Staphylococcus aureus in murine thigh and catheter-associated infection models.

    abstract::Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01422-13

    authors: Hertlein T,Sturm V,Lorenz U,Sumathy K,Jakob P,Ohlsen K

    更新日期:2014-01-01 00:00:00

  • Theaflavin-3,3'-digallate and lactic acid combinations reduce herpes simplex virus infectivity.

    abstract::The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining theaflavin-3,3'-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract. Six clinical isolates o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00659-13

    authors: Isaacs CE,Xu W

    更新日期:2013-08-01 00:00:00

  • Role of plasma proteins in pharmacokinetics of micafungin, an antifungal antibiotic, in analbuminemic rats.

    abstract::There were no significant differences in the pharmacokinetics of micafungin and expression of hepatic multidrug resistance-associated protein 2 (ABCC2/Mrp2) between analbuminemic and Sprague-Dawley rats. Micafungin bound strongly to high-density lipoprotein (HDL) and moderately to gamma globulin. These results suggest...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00396-08

    authors: Abe F,Ueyama J,Kawasumi N,Nadai M,Hayashi T,Kato M,Ohnishi M,Saito H,Takeyama N,Hasegawa T

    更新日期:2008-09-01 00:00:00

  • High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea.

    abstract::We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n=250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03090-14

    authors: Jacobsson S,Golparian D,Alm RA,Huband M,Mueller J,Jensen JS,Ohnishi M,Unemo M

    更新日期:2014-09-01 00:00:00

  • In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents.

    abstract::CP-65,207 is a new parenteral penem antibiotic with a broad spectrum that includes gram-positive, gram-negative, and anaerobic microorganisms, with MICs for 90% (MIC90s) of the majority of 1,101 clinical pathogens tested being less than or equal to 1 microgram/ml. The compound was from 10- to 100-fold more active than...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.8.1160

    authors: Gootz T,Retsema J,Girard A,Hamanaka E,Anderson M,Sokolowski S

    更新日期:1989-08-01 00:00:00

  • Ribosylation by mycobacterial strains as a new mechanism of rifampin inactivation.

    abstract::Several fast-growing Mycobacterium strains were found to inactivate rifampin. Two inactivated compounds (RIP-Ma and RIP-Mb) produced by these organisms were different from previously reported derivatives, i.e., phosphorylated or glucosylated derivatives, of the antibiotic. The structures of RIP-Ma and RIP-Mb were dete...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.4.1007

    authors: Dabbs ER,Yazawa K,Mikami Y,Miyaji M,Morisaki N,Iwasaki S,Furihata K

    更新日期:1995-04-01 00:00:00

  • Inhibition of Mycobacterium tuberculosis AhpD, an element of the peroxiredoxin defense against oxidative stress.

    abstract::The resistance of Mycobacterium tuberculosis to isoniazid (INH) is largely linked to suppression of a catalase-peroxidase enzyme (KatG) that activates INH. In the absence of KatG, antioxidant protection is provided by enhanced expression of the peroxiredoxin AhpC, which is itself reduced by AhpD, a protein with low al...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.7.2424-2430.2004

    authors: Koshkin A,Zhou XT,Kraus CN,Brenner JM,Bandyopadhyay P,Kuntz ID,Barry CE 3rd,Ortiz de Montellano PR

    更新日期:2004-07-01 00:00:00

  • In vitro antimicrobial activity of GSQ1530, a new heteroaromatic polycyclic compound.

    abstract::GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were c...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.10.3168-3174.2002

    authors: Ge Y,Difuntorum S,Touami S,Critchley I,Bürli R,Jiang V,Drazan K,Moser H

    更新日期:2002-10-01 00:00:00

  • Interactions between penicillin-binding proteins (PBPs) and two novel classes of PBP inhibitors, arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones.

    abstract::Several non-beta-lactam compounds were active against various gram-positive and gram-negative bacterial strains. The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycin-resis...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.48.3.961-969.2004

    authors: Zervosen A,Lu WP,Chen Z,White RE,Demuth TP Jr,Frère JM

    更新日期:2004-03-01 00:00:00

  • Effect of Surotomycin, a Novel Cyclic Lipopeptide Antibiotic, on Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice.

    abstract::Surotomycin (formerly called CB-183,315) is a novel, orally administered cyclic lipopeptide antibacterial in development for the treatment of Clostridium difficile infection (CDI) that has potent activity against vancomycin-resistant enterococci (VRE) but limited activity against Gram-negative bacilli, including Bacte...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02904-15

    authors: Deshpande A,Hurless K,Cadnum JL,Chesnel L,Gao L,Chan L,Kundrapu S,Polinkovsky A,Donskey CJ

    更新日期:2016-05-23 00:00:00

  • In vitro antimicrobial susceptibilities of penicillinase-producing and non-penicillinase-producing strains of Neisseria gonorrhoeae isolated in Durban, South Africa.

    abstract::The in vitro susceptibilities of 22 penicillinase-producing and 32 non-penicillinase-producing strains of Neisseria gonorrhoeae to 13 antimicrobial agents, including the new semisynthetic penicillins and cephalosporins, are reported. Ceftriaxone, ceftazidime, and cefotaxime were the most active agents tested; none of ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.26.5.770

    authors: Coovadia YM,Ramsaroop U

    更新日期:1984-11-01 00:00:00