Design, synthesis and biological evaluation of novel tetrahydroacridine pyridine- aldoxime and -amidoxime hybrids as efficient uncharged reactivators of nerve agent-inhibited human acetylcholinesterase

被引：70
|
作者：
Kliachyna, Maria [1 ]
Santoni, Gianluca [2 ,3 ,4 ]
Nussbaum, Valentin [1 ]
Renou, Julien [5 ,6 ,7 ,8 ,9 ]
Sanson, Benoit [2 ,3 ,4 ]
Colletier, Jacques-Philippe [2 ,3 ,4 ]
Arboleas, Melanie
Loiodice, Melanie [10 ]
Weik, Martin [2 ,3 ,4 ,10 ]
Jean, Ludovic [5 ,6 ,7 ,8 ,9 ]
Renard, Pierre-Yves [5 ,6 ,7 ,8 ,9 ]
Nachon, Florian [2 ,3 ,4 ,10 ]
Baati, Rachid [1 ]
机构：
[1] Univ Strasbourg, Fac Pharm, CNRS, UMR 7199, F-67401 Illkirch Graffenstaden, France
[2] Commissariat Energie Atom, Inst Biol Struct, F-38054 Grenoble, France
[3] CNRS, UMR5075, F-38027 Grenoble, France
[4] Univ Grenoble 1, F-38000 Grenoble, France
[5] Normandie Univ, COBRA, UMR 6014, F-76821 Mont St Aignan, France
[6] Normandie Univ, COBRA, FR 3038, F-76821 Mont St Aignan, France
[7] Univ Rouen, F-76821 Mont St Aignan, France
[8] INSA Rouen, F-76821 Mont St Aignan, France
[9] CNRS, F-76821 Mont St Aignan, France
[10] Inst Rech Biomed Armees, Dept Toxicol, Bretignys Orge, France
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 78卷
关键词：
Organophosphorus nerve agents; Reactivation of acetylcholinesterase; Pyridinaldoximes; Oximes; Hybrids; Tacrine; TORPEDO-CALIFORNICA ACETYLCHOLINESTERASE; ACTING OXIME REACTIVATORS; CLICK CHEMISTRY; PERIPHERAL SITE; IN-SITU; STRUCTURAL INSIGHTS; CHOLINESTERASES; BINDING; OPTIMIZATION; BRAIN;
D O I：
10.1016/j.ejmech.2014.03.044
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of new uncharged functional acetylcholinesterase (AChE) reactivators including heterodimers of tetrahydroacridine with 3-hydroxy-2-pyridine aldoximes and amidoximes has been synthesized. These novel molecules display in vitro reactivation potencies towards VX-, tabun- and paraoxon-inhibited human AChE that are superior to those of the mono- and bis-pyridinium aldoximes currently used against nerve agent and pesticide poisoning. Furthermore, these uncharged compounds exhibit a broader reactivity spectrum compared to currently approved remediation drugs. (C) 2014 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：455 / 467
页数：13
相关论文
共 9 条
  • [1] New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase
    Wei, Zhao
    Liu, Yan-qin
    Zhou, Xin-bo
    Luo, Yuan
    Huang, Chun-qian
    Wang, Yong-an
    Zheng, Zhi-bing
    Li, Song
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (24) : 5743 - 5748
  • [2] Design, synthesis and in vitro evaluation of a promising new class of bifunctional uncharged hybrid reactivators for nerve agent-inhibited human acetylcholinesterase
    Dias, Jose
    De Sousa, Julien
    Gastellier, Anne-Julie
    Rousseau, Catherine
    Courageux, Charlotte
    Timperley, Christopher
    Brown, Richard
    Santoni, Gianluca
    Weik, Martin
    Baati, Rachid
    Nachon, Florian
    JOURNAL OF NEUROCHEMISTRY, 2017, 142 : 210 - 211
  • [3] Design and discovery of potent reactivators of nerve agent-inhibited human acetylcholinesterase
    Pattabiraman, N.
    Ling, Y.
    Vinayaka, C. R.
    Luo, C.
    Chambers, C.
    Saxena, A.
    FEBS JOURNAL, 2008, 275 : 174 - 174
  • [4] Synthesis and in vitro evaluation of donepezil-based reactivators and analogues for nerve agent-inhibited human acetylcholinesterase
    Renou, Julien
    Dias, Jose
    Mercey, Guillaume
    Verdelet, Tristan
    Rousseau, Catherine
    Gastellier, Anne-Julie
    Arboleas, Melanie
    Touvrey-Loiodice, Melanie
    Baati, Rachid
    Jean, Ludovic
    Nachon, Florian
    Renard, Pierre-Yves
    RSC ADVANCES, 2016, 6 (22): : 17929 - 17940
  • [5] Conjugates of salicylaldoximes and peripheral site ligands: Novel efficient nonquaternary reactivators for nerve agent-inhibited acetylcholinesterase
    Wei, Zhao
    Liu, Yan-qin
    Wang, Sheng-zheng
    Yao, Lin
    Nie, Hui-fang
    Wang, Yong-an
    Liu, Xue-ying
    Zheng, Zhi-bing
    Li, Song
    BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (16) : 4497 - 4505
  • [6] Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon
    Kuca, Kamil
    Jun, Daniel
    Junova, Lucie
    Musilek, Kamil
    Hrabinova, Martina
    Valle da Silva, Jorge Alberto
    Ramalho, Teodorico Castro
    Valko, Marian
    Wu, Qinghua
    Nepovimova, Eugenie
    Costa Franca, Tanos Celmar
    MOLECULES, 2018, 23 (05):
  • [7] Evaluation of three novel hydroxypicolinaldehyde oximes as efficient uncharged reactivators of VX-inhibited human acetylcholinesterase
    Kovarik, Z.
    Katalinic, M.
    Jean, L.
    Renard, P. -Y.
    Renou, J.
    Gomez, C.
    FEBS JOURNAL, 2014, 281 : 279 - 279
  • [8] Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators
    Kitagawa, Daniel A. S.
    Rodrigues, Rafael B.
    Silva, Thiago N.
    dos Santos, Wellington, V
    da Rocha, Vinicius C. V.
    de Almeida, Joyce S. F. D.
    Bernardo, Leandro B.
    Carvalho-Silva, Taynara
    Ferreira, Cintia N.
    da Silva, Angelo A. T.
    Simas, Alessandro B. C.
    Nepovimova, Eugenie
    Kuca, Kamil
    Franca, Tanos C. C.
    Cavalcante, Samir F. de A.
    JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2021, 36 (01) : 1370 - 1377
  • [9] Synthesis and in vitro evaluation of novel non-oximes for the reactivation of nerve agent inhibited human acetylcholinesterase
    de Koning, Martijn C.
    Horn, Gabriele
    Worek, Franz
    van Grol, Marco
    CHEMICO-BIOLOGICAL INTERACTIONS, 2020, 326
1