3-Bromopyruvate: A novel antifungal agent against the human pathogen Cryptococcus neoformans

被引：29
作者：
Dylag, Mariusz [1 ]
Lis, Pawel [1 ]
Niedwiecka, Katarzyna [1 ]
Ko, Young H. [2 ]
Pedersen, Peter L. [3 ]
Goffeau, Andre [4 ]
Ulaszewski, Stanislaw [1 ]
机构：
[1] Univ Wroclaw, Inst Genet & Microbiol, PL-51148 Wroclaw, Poland
[2] KoDiscovery LLC, Baltimore, MD 21201 USA
[3] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[4] Catholic Univ Louvain, Inst Sci Vie, B-1348 Louvain, Belgium
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 434卷 / 02期
关键词：
3-Bromopyruvate; Antifungal activity; Cryptococcus neoformans; MULTIDRUG-RESISTANCE PROTEINS; SACCHAROMYCES-CEREVISIAE; DRUG-RESISTANCE; GLUTATHIONE; FUNGI; YEAST; TRANSPORTERS; FLUCYTOSINE; MENINGITIS; TOXICITY;
D O I：
10.1016/j.bbrc.2013.02.125
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug. (C) 2013 Elsevier Inc. All rights reserved.
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页码：322 / 327
页数：6
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