Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase

被引：13
作者：
Goncalves, Victor [1 ,3 ]
Brannigan, James A. [2 ]
Laporte, Alice [1 ]
Bell, Andrew S. [1 ]
Roberts, Shirley M. [2 ]
Wilkinson, Anthony J. [2 ]
Leatherbarrow, Robin J. [1 ,4 ]
Tate, Edward W. [1 ]
机构：
[1] Imperial Coll London, Dept Chem, London SW7 2AZ, England
[2] Univ York, Dept Chem, Struct Biol Lab, York YO10 5DD, N Yorkshire, England
[3] Univ Bourgogne Franche Comte, ICMUB, F-21000 Dijon, France
[4] Liverpool John Moores Univ, Egerton Court,2 Rodney St, Liverpool L1 2UA, Merseyside, England
来源：
MEDCHEMCOMM | 2017年 / 8卷 / 01期
基金：
英国医学研究理事会; 英国工程与自然科学研究理事会; 英国惠康基金;
关键词：
POTENTIAL-DRUG TARGET; MYRISTOYL-COA; SELECTIVE INHIBITORS; VIVAX MALARIA; DISCOVERY; DESIGN; LIGAND; LEISHMANIASIS; FALCIPARUM; PARASITES;
D O I：
10.1039/c6md00531d
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 parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N-myristoyltransferase (NMT).
引用
收藏
页码：191 / 197
页数：7
相关论文
共 35 条
  • [1] [Anonymous], PLOS NEGL TROP DIS
  • [2] Selective Inhibitors of Protozoan Protein N-myristoyltransferases as Starting Points for Tropical Disease Medicinal Chemistry Programs
    Bell, Andrew S.
    Mills, James E.
    Williams, Gareth P.
    Brannigan, James A.
    Wilkinson, Anthony J.
    Parkinson, Tanya
    Leatherbarrow, Robin J.
    Tate, Edward W.
    Holder, Anthony A.
    Smith, Deborah F.
    [J]. PLOS NEGLECTED TROPICAL DISEASES, 2012, 6 (04):
  • [3] Diverse modes of binding in structures of Leishmania major N-myristoyltransferase with selective inhibitors
    Brannigan, James A.
    Roberts, Shirley M.
    Bell, Andrew S.
    Hutton, Jennie A.
    Hodgkinson, Michael R.
    Tate, Edward W.
    Leatherbarrow, Robin J.
    Smith, Deborah F.
    Wilkinson, Anthony J.
    [J]. IUCRJ, 2014, 1 : 250 - 260
  • [4] N-Myristoyltransferase from Leishmania donovani: Structural and Functional Characterisation of a Potential Drug Target for Visceral Leishmaniasis
    Brannigan, James A.
    Smith, Barbara A.
    Yu, Zhiyong
    Brzozowski, Andrzej M.
    Hodgkinson, Michael R.
    Maroof, Asher
    Price, Helen P.
    Meier, Franziska
    Leatherbarrow, Robin J.
    Tate, Edward W.
    Smith, Deborah F.
    Wilkinson, Anthony J.
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2010, 396 (04) : 985 - 999
  • [5] MYRISTYLATION OF PICORNAVIRUS CAPSID PROTEIN VP4 AND ITS STRUCTURAL SIGNIFICANCE
    CHOW, M
    NEWMAN, JFE
    FILMAN, D
    HOGLE, JM
    ROWLANDS, DJ
    BROWN, F
    [J]. NATURE, 1987, 327 (6122) : 482 - 486
  • [6] DESIGN AND SYNTHESES OF POTENT AND SELECTIVE DIPEPTIDE INHIBITORS OF CANDIDA-ALBICANS MYRISTOYL-COA-PROTEIN N-MYRISTOYLTRANSFERASE
    DEVADAS, B
    ZUPEC, ME
    FREEMAN, SK
    BROWN, DL
    NAGARAJAN, S
    SIKORSKI, JA
    MCWHERTER, CA
    GETMAN, DP
    GORDON, JI
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (11) : 1837 - 1840
  • [7] N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
    Frearson, Julie A.
    Brand, Stephen
    McElroy, Stuart P.
    Cleghorn, Laura A. T.
    Smid, Ondrej
    Stojanovski, Laste
    Price, Helen P.
    Guther, M. Lucia S.
    Torrie, Leah S.
    Robinson, David A.
    Hallyburton, Irene
    Mpamhanga, Chidochangu P.
    Brannigan, James A.
    Wilkinson, Anthony J.
    Hodgkinson, Michael
    Hui, Raymond
    Qiu, Wei
    Raimi, Olawale G.
    van Aalten, Daan M. F.
    Brenk, Ruth
    Gilbert, Ian H.
    Read, Kevin D.
    Fairlamb, Alan H.
    Ferguson, Michael A. J.
    Smith, Deborah F.
    Wyatt, Paul G.
    [J]. NATURE, 2010, 464 (7289) : 728 - U100
  • [8] Antifungals targeted to protein modification: focus on protein N-myristoyltransferase
    Georgopapadakou, NH
    [J]. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2002, 11 (08) : 1117 - 1125
  • [9] Discovery of Plasmodium vivax N-Myristoyltransferase Inhibitors: Screening, Synthesis, and Structural Characterization of their Binding Mode
    Goncalves, Victor
    Brannigan, James A.
    Whalley, David
    Ansell, Keith H.
    Saxty, Barbara
    Holder, Anthony A.
    Wilkinson, Anthony J.
    Tate, Edward W.
    Leatherbarrow, Robin J.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (07) : 3578 - 3582
  • [10] A fluorescence-based assay for N-myristoyltransferase activity
    Goncalves, Victor
    Brannigan, James A.
    Thinon, Emmanuelle
    Olaleye, Tayo O.
    Serwa, Remigiusz
    Lanzarone, Salvatore
    Wilkinson, Anthony J.
    Tate, Edward W.
    Leatherbarrow, Robin J.
    [J]. ANALYTICAL BIOCHEMISTRY, 2012, 421 (01) : 342 - 344
1234