Reactivators of acetylcholinesterase inhibited by organophosphorus nerve agents

Accounts of Chemical Research

Volumn 45, Issue 5, 2012, Pages 756-766

  Mercey, Guillaume ^a,b   Verdelet, Tristan ^a,b   Renou, Julien ^a,b   Kliachyna, Maria ^c   Baati, Rachid ^c   Nachon, Florian ^d   Jean, Ludovic ^a,b   Renard, Pierre Yves ^a,b,e  

^a Normandie Université   (France)

^b UNIVERSITÉ DE ROUEN   (France)

^c UNIVERSITÉ DE STRASBOURG   (France)

^d INSTITUT DE RECHERCHE BIOMÉDICALE DES ARMÉES   (France)

^e INSTITUT UNIVERSITAIRE DE FRANCE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDOTE; CHEMICAL WARFARE AGENT; CHOLINESTERASE INHIBITOR; CHOLINESTERASE REACTIVATOR; NANOPARTICLE; ORGANOPHOSPHORUS COMPOUND; OXIME; PYRIDINIUM DERIVATIVE;

ARTICLE; BLOOD BRAIN BARRIER; CHEMISTRY; DRUG DESIGN; DRUG EFFECT; HUMAN; STRUCTURE ACTIVITY RELATION;

ANTIDOTES; BLOOD-BRAIN BARRIER; CHEMICAL WARFARE AGENTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASE REACTIVATORS; DRUG DESIGN; HUMANS; NANOPARTICLES; ORGANOPHOSPHORUS COMPOUNDS; OXIMES; PYRIDINIUM COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84861180356     PISSN: 00014842     EISSN: 15204898     Source Type: Journal    
DOI: 10.1021/ar2002864     Document Type: Article

References (74)

1. Eddleston, M.; Buckley, N. A.; Eyer, P.; Dawson, A.-H. Management of acute organophosphorus pesticide poisoning Lancet 2008, 371, 597-607
2. JokanovicÌ, M.; Prostran, M. Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds Curr. Med. Chem. 2009, 16, 2177-2188
3. Jung, Y.-S.; Kuča, K. Current study on the development of bis-pyridinium oxime reactivators for the antidotal treatment of poisoning by toxic organophosphorus agents Curr. Org. Chem. 2011, 15, 433-444
4. Musilek, K.; Dolezal, M.; Gunn-Moore, F.; Kuča, K. Design, evaluation and structure-activity relationship studies of the AChE reactivators against organophosphorus pesticides Med. Res. Rev. 2009, 31, 548-575
5. Watson, A.; Opresko, D.; Young, R.; Hauschild, V.; King, J.; Bakshi, K. Organophosphate Nerve Agents. In Handbook of Toxicology of Chemical Warfare Agents; Gupta, R. C., Ed.; Academic Press Inc: London, 2009; Chapter 6.
6. Maxwell, D. M.; Brecht, K. M.; Koplovitz, I.; Sweeney, R. E. Acetylcholinesterase inhibition: Does it explain the toxicity of organophosphorus compounds? Arch. Toxicol. 2006, 80, 756-760
7. Quinn, D. M. Acetylcholinesterase: Enzyme structure, reaction dynamics, and virtual transition states Chem. Rev. 1987, 87, 955-979
8. Millard, C. B.; Koellner, G.; Ordentlich, A.; Shafferman, A.; Silman, I.; Sussman, J. L. Reaction products of acetylcholinesterase and VX reveal a mobile histidine in the catalytic triad J. Am. Chem. Soc. 1999, 121, 9883-9884
9. Carletti, E.; Colletier, J.-P.; Dupeux, F.; Trovaslet, M.; Masson, P.; Nachon, F. Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation J. Med. Chem. 2010, 53, 4002-4008
10. Sanson, B.; Nachon, F.; Colletier, J.-P.; Froment, M.-T.; Toker, L.; Greenblatt, H. M.; Sussman, J. L.; Ashani, Y.; Masson, P.; Silman, I.; Weik, M. Crystallographic snapshots of nonaged and aged conjugates of soman with acetylcholinesterase, and of a ternary complex of the aged conjugate with pralidoxime J. Med. Chem. 2009, 52, 7593-7603
11. Worek, F.; Diepold, C.; Eyer, P. Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics Arch. Toxicol. 1999, 73, 7-14
12. Trovaslet-Leroy, M.; Musilova, L.; Renault, F.; Brazzolotto, X.; Misik, J.; Novotny, L.; Froment, M.-T.; Gillon, E.; Loiodice, M.; Verdier, L.; Masson, P.; Rochu, D.; Jun, D.; Nachon, F. Organophosphate hydrolases as catalytic bioscavengers of organophosphorus nerve agents Toxicol. Lett. 2011, 206, 14-23
13. Masson, P.; Nachon, F.; Lockridge, O. Structural approach to the aging of phosphylated cholinesterases Chem. Biol. Interact. 2010, 187, 157-162
14. Worek, F.; Thiermann, H.; Szinicz, L.; Eyer, P. Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes Biochem. Pharmacol. 2004, 68, 2237-2248
15. 31P NMR spectroscopy Biochemistry 1993, 32, 13441-13450
16. Wilson, I. B. Acetylcholinesterase. XI. Reversibility of tetraethyl pyrophosphate J. Biol. Chem. 1951, 190, 111-117
17. Wilson, I. B.; Meislich, E. K. Reactivation of acetylcholinesterase inhibted by alkylphosphates J. Am. Chem. Soc. 1953, 75, 4628-4629
18. Childs, A. F.; Davies, D. R.; Green, A. L.; Rutland, J. P. The reactivation by oximes and hydroxamic acids of cholinesterase inhibited by organo-phosphorus compounds Br. J. Pharmacol. 1955, 10, 462-465
19. Green, A. L.; Smith, H. J. The reactivation of cholinesterase inhibited with organophosphorus compounds. I. Reactivation by 2-oxoaldoximes Biochem. J. 1958, 68, 28-31
20. Wilson, I. B.; Ginsburg, B. A powerful reactivator of alkylphosphate-inhibited acetylcholinesterase Biochim. Biophys. Acta 1955, 18, 168-170
21. Wilson, I. B.; Ginsburg, S. Reactivation of alkylphosphate inhibited acetylcholinesterase by bis quaternary derivatives of 2-PAM and 4-PAM Biochem. Pharmacol. 1959, 1, 200-206
22. Luettringhaus, A.; Hagedorn, I. Quaternary hydroxyiminomethylpyridinium salts. The dischloride of bis-(4-hydroxyiminomethyl-1-pyridinium-methyl)-ether (lueh6), a new reactivator of acetylcholinesterase inhibited by organic phosphoric acid esters Arzneimittelforschung 1964, 14, 1-5
23. Hagedorn, I.; Gundel, W. H.; Schoene, K. Reactivation of phosphorylated acetylcholine esterase with oximes: contribution to the study of the reaction course Arzneimittelforschung 1969, 19, 603-606
24. Eyer, P.; Hagedorn, I.; Klimmek, R.; Lippstreu, P.; Löffler, M.; Oldiges, H.; Spöhrer, U.; Steidl, I.; Szinicz, L.; Worek, F. HLö-7 dimethanesulfonate, a potent bispyridinium-dioxime against anticholinesterases Arch. Toxicol. 1992, 66, 603-621
25. Worek, F.; Eyer, P.; Aurbek, N.; Szinicz, L.; Thiermann, H. Recent advances in evaluation of oxime efficacy in nerve agent poisoning by in vitro analysis Toxicol. Appl. Pharmacol. 2007, 219, 226-234
26. Worek, F.; Aurbek, N.; Koller, M.; Becker, C.; Eyer., P.; Thiermann, H. Kinetic analysis of reactivation and aging of human acetylcholinesterase inhibited by different phosphoramidates Biochem. Pharmacol. 2007, 73, 1807-1817
27. Carletti, E.; Aurbek, N.; Gillon, E.; Loiodice, M.; Nicolet, Y.; Fontecilla-Camps, J. C.; Masson, P.; Thiermann, H.; Nachon, F.; Worek, F. Structure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun Biochem. J. 2009, 421, 97-106
28. Terrier, F.; Rodriguez-Dafonte, P.; Le Guével, E.; Moutiers, G. Revisiting the reactivity of oximate α-nucleophiles with electrophilic phosphorus centers. Relevance to detoxification of sarin, soman and DFP under mild conditions Org. Biomol. Chem. 2006, 4, 4352-4363
29. Ekström, F.; Astot, J. C.; Pang, Y. P. Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes Clin. Pharmacol. Ther. 2007, 82, 282-293
30. Hörnberg, A.; Artursson, E.; Wärme, R.; Pang, Y. P.; Ekström, F. Crystal structures of oxime-bound fenamiphos- acetylcholinesterases: reactivation involving flipping of the His447 ring to form a reactive Glu334-His447-oxime triad Biochem. Pharmacol. 2010, 79, 507-515
31. Taylor, P.; Kovarik, Z.; Reiner, E.; RadicÌ, Z. Acetylcholinesterase: Converting a vulnerable target to a template for antidotes and detection of inhibitor exposure Toxicology 2007, 233, 70-78
32. Hörnberg, A.; Artursson, E.; Wärme, R.; Pang, Y. P.; Ekström, F. Crystal structures of oxime-bound fenamiphos- acetylcholinesterases: reactivation involving flipping of the His447 ring to form a reactive Glu334-His447-oxime triad Biochem. Pharmacol. 2010, 79, 507-515
33. Ekström, F.; Hörnberg, A.; Artursson, E.; Hammarström, L. G.; Schneider, G.; Pang, Y. P. Structure of HI-6/sarin-acetylcholinesterase determined by X-ray crystallography and molecular dynamics simulation: Reactivator mechanism and design PLoS One 2009, 4, e5957
34. Nachon, F.; Carletti, E.; Worek, F.; Masson, P. Aging mechanism of butyrylcholinesterase inhibited by an N-methyl analogue of tabun: Implications of the trigonal-bipyramidal transition state rearrangement for the phosphylation or reactivation of cholinesterases Chem. Biol. Interact. 2010, 187, 44-48
35. Ohta, H.; Ohmori, T.; Suzuki, S.; Ikegaya, H.; Sakurada, K.; Takatori, T. New Safe method for preparation of sarin-exposed human erythrocytes acetylcholinesterase using non-toxic and stable sarin analogue isopropyl p-nitrophenyl methylphosphonate and its application to evaluation of nerve agent antidotes Pharm. Res. 2006, 23, 2827-2833
36. Okuno, S.; Sakurada, K.; Ohta, H.; Ikegaya, H.; Kazui, Y.; Akutsu, T.; Takatori, T.; Iwadate, K. Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS Toxicol. Appl. Pharmacol. 2008, 227, 8-15
37. Cabal, J.; Kuča, K.; Kassa, J. Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase Basic Clin. Pharmacol. Toxicol. 2004, 95, 81-86
38. Musilek, K.; Komloova, M.; Holas, O.; Horova, A.; Pohanka, M.; Gunn-Moore, F.; Dohnal, V.; Dolezal, M.; Kuča, K. Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage - Preparation, in vitro screening and molecular docking Bioorg. Med. Chem. 2011, 19, 754-762
39. Kuča, K.; BielavskyÌ, J.; Cabal, J.; Kassa, J. Synthesis of a new reactivator of tabun-inhibited acetylcholinesterase Bioorg. Med. Chem. Lett. 2003, 13, 3545-3547
40. Kassa, J.; Kuča, K.; Karasová, J.; Musilek, K. The development of new oximes and the evaluation of their reactivating, therapeutic and neuroprotective efficacy against tabun Mini Rev. Med. Chem. 2008, 8, 1134-1143
41. Artursson, E.; Akfur, C.; Hornberg, A.; Worek, F.; Ekström, F. Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis Toxicology 2009, 265, 108-114
42. Ekström, F.; Pang, Y.-P.; Boman, M.; Artusson, E.; Akfur, C.; Börjegren, S. Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime: Structural basis for differences in the ability to reactivate tabun conjugates Biochem. Pharmacol. 2006, 72, 597-607
43. Kuča, K.; Cabal, J.; Jung, Y. S.; Musilek, K.; Soukup, O.; Jun, D.; Pohanka, M.; Musilova, L.; Karasová, J.; NovotnyÌ, L.; Hrabinova, M. Reactivation of human brain homogenate cholinesterases inhibited by tabun using newly developed oximes K117 and K127 Basic Clin. Pharmacol. Toxicol. 2009, 105, 207-210
44. Acharya, J.; Dubey, D. K.; Srivastava, A. K.; Raza, S. K. In vitro evaluation of bis-pyridinium oximes bearing methoxy alkane linker as reactivators of sarin inhibited human acetylcholinesterase Toxicol. in Vitro 2010, 24, 1797-1802
45. Musilek, K.; Jun, D.; Cabal, J.; Kassa, J.; Gunn-Moore, F.; Kuča, K. Design of a potent reactivator of tabun-inhibited acetylcholinesterase synthesis and evaluation of (E)-1-(4-Carbamoylpyridinium)-4-(4- hydroxyiminomethylpyridinium)-but-2-ene Dibromide (K203) J. Med. Chem. 2007, 50, 5514-5518
46. Musilek, K.; Holas, O.; Misik, J.; Pohanka, M.; Novotny, L.; Dohnal, V.; Opletalova, V.; Kuča, K. Monooxime-monocarbamoyl bispyridinium xylene-linked reactivators of acetylcholinesterase - Synthesis, in vitro and toxicity evaluation, and docking studies ChemMedChem 2010, 5, 247-254
47. Acharya, J.; Dubey, D. K.; Srivastava, A. K.; Raza, S. K. In vitro reactivation of sarin-inhibited human acetylcholinesterase (AChE) by bis-pyridinium oximes connected by xylene linkers Toxicol. in Vitro 2011, 25, 251-256
48. Ballabh, P.; Bruan, A.; Nedergaard, M. The blood-brain barrier: An overview structure, regulation, and clinical implications Neurobiol. Dis. 2004, 16, 1-13
49. Abbott, N. J.; Ronnback, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier Nat. Rev. Neurosci. 2006, 7, 41-53
50. Lorke, D. E.; Kalasz, H.; Petroianu, G. A.; Tekes, K. Entry of oximes into the brain: A review Curr. Med. Chem. 2008, 15, 743-753
51. Sakurada, K.; Matsubara, K.; Shimizu, K.; Shiono, H.; Seto, Y.; Tsuge, K.; Yoshino, M.; Sakai, I.; Mukoyama, H.; Takatori, T. Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier Neurochem. Res. 2003, 28, 1401-1407
52. Cook, A. M.; Mieure, K. D.; Owen, R. D.; Pesaturo, A. B.; Hatton, J. Intracerebroventricular administration of drugs Pharmacotherapy 2009, 29, 832-845
53. Bradley, W. G., Jr. MR-guided focused ultrasound: A potentially disruptive technology J. Am. Coll. Radiol. 2009, 6, 510-513
54. Neuwelt, E. A.; Frenkel, E. P.; Diehl, J. T.; Maravilla, K. R.; Vu, L. H.; Clark, W. K.; Rapoport, S. I.; Barnett, P. A.; Hill, S. A.; Lewis, S. E.; Ehle, A. L.; Beyer, C. W., Jr.; Moore, R. J. Osmotic blood-brain barrier disruption: A New means of increasing chemotherapeutic agent delivery Trans. Am. Neurol. Assoc. 1979, 104, 256-260
55. Wagner, S.; Kufleitner, J.; Zensi, A.; Dadparvar, M.; Wien, S.; Bungert, J.; Vogel, T.; Worek, F.; Kreuter, J.; von Briesen, A. Nanoparticulate transport of oximes over an in vitro blood-brain barrier model PLoS One 2010, 5 e14213
56. Joosen, M. J. A.; van der Schans, M. J.; van Dijk, C. G. M.; Kuijpers, W. C.; Wortelboer, H. M.; van Helden, H. P. M Increasing oxime efficacy by blood-brain barrier modulation Toxicol. Lett. 2011, 206, 67-71
57. Carman, A. J.; Mills, J. H.; Krenz, A.; Kim, D. G.; Bynoe, M. S. Adenosine receptor signaling modulates permeability of the blood-brain barrier J. Neurosci. 2011, 31, 13272-13280
58. Jeong, H. C.; Kang, N. S.; Park, N. J.; Yum, E. K.; Jung, Y. S. Reactivation potency of fluorinated pyridinium oximes for acetylcholinesterases inhibited by paraoxon organophosphorus agent Bioorg. Med. Chem. Lett. 2009, 19, 1214-1217
59. Jeong, H. C.; Park, N. J.; Chae, C. H.; Musilek, K.; Kassa, J.; Kuca, K.; Jung, Y. S. Fluorinated pyridinium oximes as potential reactivators for acetylcholinesterases inhibited by paraoxon organophosphorus agent Bioorg. Med. Chem. 2009, 17, 6213-6217
60. Heldman, E.; Ashani, Y.; Raveh, L.; Rachaman, E. S. Sugar conjugates of pyridinium aldoximes as antidotes against organophosphonate poisoning Carbohydr. Res. 1986, 151, 337-347
61. Garcia, G. E.; Campbell, A. J.; Olson, J.; Moorad-Doctor, D.; Morthole, V. I. Novel oximes as blood-brain barrier penetrating cholinesterase reactivators Chem. Biol. Interact. 2010, 187, 199-206
62. Shek, E.; Higuchi, T.; Bodor, N. Improved delivery through biological membranes. 2. Distribution, excretion, and metabolism of N -methyl-1,6- dihydropyridine-2-carbaldoxime hydrochloride, a pro-drug of N -methylpyridinium-2-carbaldoxime chloride J. Med. Chem. 1976, 19, 108-112
63. Demar, J. C.; Clarkson, E. D.; Ratcliffe, R. H.; Campbell, A. J.; Thangavelu, S. G.; Herdman, C. A.; Leader, H.; Schulz, S. M.; Marek, E.; Medynets, M. A.; Ku, T. C.; Evans, S. A.; Khan, F. A.; Owens, R. R.; Nambiar, M. P.; Gordon, R. K. Pro-2-PAM therapy for central and peripheral cholinesterases Chem. Biol. Interact. 2010, 187, 191-198
64. Shih, T. M.; Skovira, J. W.; O'Donnell, J. C.; McDonough, J. H. Central acetylcholinesterase reactivation by oximes improves survival and terminates seizures following nerve agent intoxication Adv. Stud. Biol. 2009, 1, 155-196
65. Skovira, J. W.; O'Donnell, J. C.; Koplovitz, I.; Kan, R. K.; McDonough, J. H.; Shih, T. M. Reactivation of brain acetylcholinesterase by monoisonitrosoacetone increases the therapeutic efficacy against nerve agents in guinea pigs Chem. Biol. Interact. 2010, 187, 318-324
66. de Koning, M. C.; van Grol, M.; Noort, D. Peripheral site ligand conjugation to a non-quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase Toxicol. Lett. 2011, 206, 54-59
67. Sit, R. K.; RadicÌ, Z.; Gerardi, V.; Zhang, L.; Garcia, E.; KatalinicÌ, M.; Amitai, G.; Kovarik, Z.; Fokin, V. V.; Sharpless, K. B.; Taylor, P. New structural scaffolds for centrally acting oxime reactivators of phosphylated cholinesterases J. Biol. Chem. 2011, 286, 19422-19430
68. Saint-André, G.; Kliachyna, M.; Kodepelly, S.; Louise-Leriche, L.; Gillon, E.; Renard, P.-Y.; Nachon, F.; Baati, R.; Wagner, A. Design, synthesis and evaluation of new α-nucleophiles for the hydrolysis of organophosphorus nerve agents: application to the reactivation of phosphorylated acetylcholinesterase Tetrahedron 2011, 67, 6352-6361
69. Mercey, G.; Verdelet, T.; Saint-André, G.; Gillon, E.; Wagner, A.; Baati, R.; Jean, L.; Nachon, F.; Renard, P.-Y. First efficient uncharged reactivators for the dephosphorylation of poisoned human acetylcholinesterase Chem. Commun. 2011, 47, 5295-5297
70. Ashani, Y.; Bhattacharjee, A. K.; Leader, H.; Saxena, A.; Doctor, B. P. Inhibition of cholinesterases with cationic phosphonyl oximes highlights distinctive properties of the charged pyridine groups of quaternary oxime reactivators Biochem. Pharmacol. 2003, 66, 191-202
71. Louise-Leriche, L.; Pǎunescu, E.; Saint-André, G.; Baati, R.; Romieu, A.; Wagner, A.; Renard, P.-Y. A HTS assay for the detection of organophosphorus nerve agents scavengers Chem. - Eur. J. 2010, 16, 3510-3523
72. Kalisiak, J.; Ralph, E. C.; Zhang, J.; Cashman, J. R. Amidine-oximes: Reactivators for organophosphate exposure J. Med. Chem. 2011, 54, 3319-3330
73. Antonijevic, B.; Stojiljkovic, M. P. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning Clin. Med. Res. 2007, 5, 71-82
74. Worek, F.; Aurbek, N.; Thiermann, H. Reactivation of organophosphate- inhibited human AChE by combinaisons of obidoxime and HI 6 in vitro J. Appl. Toxicol. 2007, 27, 582-588