Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase

被引：32
作者：
Clinch, Keith [1 ]
Crump, Douglas R. [1 ]
Evans, Gary B. [1 ]
Hazleton, Keith Z. [2 ]
Mason, Jennifer M. [1 ]
Schramm, Vern L. [2 ]
Tyler, Peter C. [1 ]
机构：
[1] Ind Res Ltd, Carbohydrate Chem, Lower Hutt 5040, New Zealand
[2] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 17期
关键词：
Phosphoribosyltransferase; Malaria; HGXPRTase; Purine salvage; Protozoa; TRANSITION-STATE ANALOG; ANTI-PROTOZOAL AGENTS; NUCLEOSIDE PHOSPHONATES; PYRIMIDINE METABOLISM; POTENTIAL INHIBITORS; PURINE; PHOSPHORYLASE; PHOSPHOSERINE; MALARIA; ENZYMES;
D O I：
10.1016/j.bmc.2013.02.016
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：
The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5629 / 5646
页数：18
相关论文
共 50 条
  • [11] Dondoni A., 2004, ORG SYNTH, V10, P320
  • [12] Synthesis of second-generation transition state analogues of human purine nucleoside phosphorylase
    Evans, GB
    Furneaux, RH
    Lewandowicz, A
    Schramm, VL
    Tyler, PC
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (24) : 5271 - 5276
  • [13] 2-[2-Substituted-3-(3,4-dichlorobenzylamino)propylamino]-1H-quinolin-4-ones as Staphylococcus aureus methionyl-tRNA synthetase inhibitors
    Farhanullah, R.
    Kang, Taehee
    Yoon, Eun-Jung
    Choi, Eun-Chil
    Kim, Sunghoon
    Lee, Jeewoo
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (01) : 239 - 250
  • [14] Synthesis and biological evaluation of γ-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists
    Foss, Frank W., Jr.
    Snyder, Ashley H.
    Davis, Michael D.
    Rouse, Michael
    Okusa, Mark D.
    Lynch, Kevin R.
    Macdonald, Timothy L.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (02) : 663 - 677
  • [15] Synthesis of β-Hydroxyphosphonate and 1,2-Dihydroxy Acyclic Nucleoside Analogs via 1,3-Dipolar Cycloaddition Strategy
    Ganesan, M.
    Muraleedharan, K. M.
    [J]. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2010, 29 (02) : 91 - 96
  • [16] THE SYNTHESIS AND CONFIGURATIONAL STABILITY OF DIFFERENTIALLY PROTECTED BETA-HYDROXY-ALPHA-AMINO ALDEHYDES
    GARNER, P
    PARK, JM
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1987, 52 (12) : 2361 - 2364
  • [17] 9-DEAZAPURINE NUCLEOSIDES - THE SYNTHESIS OF CERTAIN N-5-2'-DEOXY-BETA-D-ERYTHROPENTOFURANOSYL AND N-5-BETA-D-ARABINOFURANOSYLPYRROLO[3,2-D]PYRIMIDINES
    GIRGIS, NS
    COTTAM, HB
    LARSON, SB
    ROBINS, RK
    [J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 1987, 24 (03) : 821 - 827
  • [18] Acyclic Immucillin Phosphonates: Second-Generation Inhibitors of Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase
    Hazleton, Keith Z.
    Ho, Meng-Chiao
    Cassera, Maria B.
    Clinch, Keith
    Crump, Douglas R.
    Rosario, Irving, Jr.
    Merino, Emilio F.
    Almo, Steve C.
    Tyler, Peter C.
    Schramm, Vern L.
    [J]. CHEMISTRY & BIOLOGY, 2012, 19 (06): : 721 - 730
  • [19] Phosphonate diester and phosphonamide synthesis. Reaction coordinate analysis by P-31 NMR spectroscopy: Identification of pyrophosphonate anhydrides and highly reactive phosphonylammonium salts
    Hirschmann, R
    Yager, KM
    Taylor, CM
    Witherington, J
    Sprengeler, PA
    Phillips, BW
    Moore, W
    Smith, AB
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (35) : 8177 - 8190
  • [20] Four generations of transition-state analogues for human purine nucleoside phosphorylase
    Ho, Meng-Chiao
    Shi, Wuxian
    Rinaldo-Matthis, Agnes
    Tyler, Peter C.
    Evans, Gary B.
    Clinch, Keith
    Almo, Steven C.
    Schramm, Vern L.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (11) : 4805 - 4812
12345