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
  • [1] D-glucose-based azacrown ethers with a phosphonoalkyl side chain:: application as enantioselective phase transfer catalysts
    Bakó, P
    Novák, T
    Ludányi, K
    Pete, B
    Toke, L
    Keglevich, G
    [J]. TETRAHEDRON-ASYMMETRY, 1999, 10 (12) : 2373 - 2380
  • [2] Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age
    Bejon, Philip
    Lusingu, John
    Olotu, Ally
    Leach, Amanda
    Lievens, Marc
    Vekemans, Johan
    Mshamu, Salum
    Lang, Trudie
    Gould, Jayne
    Dubois, Marie-Claude
    Demoitie, Marie-Ange
    Stallaert, Jean-Francois
    Vansadia, Preeti
    Carter, Terrell
    Njuguna, Patricia
    Awuondo, Ken O.
    Malabeja, Anangisye
    Abdul, Omar
    Gesase, Samwel
    Mturi, Neema
    Drakeley, Chris J.
    Savarese, Barbara
    Villafana, Tonya
    Ballou, W. Ripley
    Cohen, Joe
    Riley, Eleanor M.
    Lemnge, Martha M.
    Marsh, Kevin
    von Seidlein, Lorenz
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (24) : 2521 - 2532
  • [3] Ready access to fluorinated phosphonate mimics of secondary phosphates. Synthesis of the (alpha,alpha-difluoroalkyl) phosphonate analogues of L-phosphoserine, L-phosphoallothreonine, and L-phosphothreonine
    Berkowitz, DB
    Eggen, M
    Shen, QR
    Shoemaker, RK
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (14) : 4666 - 4675
  • [4] Erythrocytic Adenosine Monophosphate as an Alternative Purine Source in Plasmodium falciparum
    Cassera, Maria B.
    Hazleton, Keith Z.
    Riegelhaupt, Paul M.
    Merino, Emilio F.
    Luo, Minkui
    Akabas, Myles H.
    Schramm, Vern L.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (47) : 32889 - 32899
  • [5] Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model
    Cassera, Maria B.
    Hazleton, Keith Z.
    Merino, Emilio F.
    Obaldia, Nicanor, III
    Ho, Meng-Chiao
    Murkin, Andrew S.
    DePinto, Richard
    Gutierrez, Jemy A.
    Almo, Steven C.
    Evans, Gary B.
    Babu, Yarlagadda S.
    Schramm, Vern L.
    [J]. PLOS ONE, 2011, 6 (11):
  • [6] A Major Genome Region Underlying Artemisinin Resistance in Malaria
    Cheeseman, Ian H.
    Miller, Becky A.
    Nair, Shalini
    Nkhoma, Standwell
    Tan, Asako
    Tan, John C.
    Al Saai, Salma
    Phyo, Aung Pyae
    Moo, Carit Ler
    Lwin, Khin Maung
    McGready, Rose
    Ashley, Elizabeth
    Imwong, Mallika
    Stepniewska, Kasia
    Yi, Poravuth
    Dondorp, Arjen M.
    Mayxay, Mayfong
    Newton, Paul N.
    White, Nicholas J.
    Nosten, Francois
    Ferdig, Michael T.
    Anderson, Timothy J. C.
    [J]. SCIENCE, 2012, 336 (6077) : 79 - 82
  • [7] Highly efficient synthesis of enantiomerically enriched 2-hydroxymethylaziridines by enzymatic desymmetrization
    Choi, Jun Young
    Borch, Richard F.
    [J]. ORGANIC LETTERS, 2007, 9 (02) : 215 - 218
  • [8] Clinch K., 2009, [No title captured], Patent No. [WO 2009/082247, 2009082247]
  • [9] Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics
    Clinch, Keith
    Evans, Gary B.
    Froehlich, Richard F. G.
    Gulab, Shivali A.
    Gutierrez, Jemy A.
    Mason, Jennifer M.
    Schramm, Vern L.
    Tyler, Peter C.
    Woolhouse, Anthony D.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (17) : 5181 - 5187
  • [10] Third-Generation Immucillins: Syntheses and Bioactivities of Acyclic Immucillin Inhibitors of Human Purine Nucleoside Phosphorylase
    Clinch, Keith
    Evans, Gary B.
    Froehlich, Richard F. G.
    Furneaux, Richard H.
    Kelly, Peter M.
    Legentil, Laurent
    Murkin, Andrew S.
    Li, Lei
    Schramm, Vern L.
    Tyler, Peter C.
    Woolhouse, Anthony D.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (04) : 1126 - 1143
12345