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Review

Progress in acetylcholinesterase reactivators and in the treatment of organophosphorus intoxication: a patent review (2006–2016)

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Pages 971-985 | Received 09 Oct 2016, Accepted 01 Jun 2017, Published online: 06 Jun 2017

References

  • Tougu V. Acetylcholinesterase: mechanism of catalysis and inhibition. Curr Med Chem-Cent Nerv Syst Agents. 2001;1:155–170.
  • Lushington GH, Guo J-X, Hurley MM. Acetylcholinesterase: molecular modeling with the whole toolkit. Curr Top Med Chem. 2006;6:57–73.
  • Lockridge O. Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharmacol Ther. 2015;148:34–46.
  • Maurice T, Strehaiano M, Siméon N, et al. Learning performances and vulnerability to amyloid toxicity in the butyrylcholinesterase knockout mouse. Behav Brain Res. 2016;296:351–360.
  • Johnson G, Moore SW. The peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design. Curr Pharm Des. 2006;12:217–225.
  • Sussman JL, Harel M, Frolow F, et al. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 1991;253:872–879.
  • Berg L, Andersson CD, Artursson E, et al. Targeting acetylcholinesterase: identification of chemical leads by high throughput screening, structure determination and molecular modeling. Plos ONE. 2011;6:e26039.
  • Marrs TC. Organophosphate poisoning. Pharmacol Ther. 1993;58:51–66.
  • Korabecny J, Andrs M, Nepovimova E, et al. 7-Methoxytacrine-p-anisidine hybrids as novel dual binding site acetylcholinesterase inhibitors for Alzheimer’s disease treatment. Mol Basel Switz. 2015;20:22084–22101.
  • Nepovimova E, Korabecny J, Dolezal R, et al. Tacrine-Trolox hybrids: a novel class of centrally active, nonhepatotoxic multi-target-directed ligands exerting anticholinesterase and antioxidant activities with low in vivo toxicity. J Med Chem. 2015;58:8985–9003.
  • Alonso D, Dorronsoro I, Rubio L, et al. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg Med Chem. 2005;13:6588–6597.
  • Komloova M, Musilek K, Dolezal M, et al. Structure-activity relationship of quaternary acetylcholinesterase inhibitors - outlook for early myasthenia gravis treatment. Curr Med Chem. 2010;17:1810–1824.
  • Agarwal R, Shukla SK, Dharmani S, et al. Biological warfare–an emerging threat. J Assoc Physicians India. 2004;52:733–738.
  • Pita R, Domingo J. The use of chemical weapons in the Syrian conflict. Toxics. 2014;2:391–402.
  • Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet Lond Engl. 2008;371:597–607.
  • Segall Y, Waysbort D, Barak D, et al. Direct observation and elucidation of the structures of aged and nonaged phosphorylated cholinesterases by phosphorus-31 NMR spectroscopy. Biochemistry (Mosc). 1993;32:13441–13450.
  • Masson P, Nachon F, Lockridge O. Structural approach to the aging of phosphylated cholinesterases. Chem Biol Interact. 2010;187:157–162.
  • Mercey G, Verdelet T, Renou J, et al. Reactivators of acetylcholinesterase inhibited by organophosphorus nerve agents. Acc Chem Res. 2012;45:756–766.
  • Watson A, Opresko D, Young RA, et al. Organophosphate nerve agents. In: Ramesh C. Gupta, Editor. Handbook of Toxicology of Chemical Warfare Agents. 2nded. London: Academic Press; 2015. p. 87–109.
  • Kassa J. Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J Toxicol Clin Toxicol. 2002;40:803–816.
  • Bajgar J, Fusek J, Kuca K, et al. Treatment of organophosphate intoxication using cholinesterase reactivators: facts and fiction. Mini Rev Med Chem. 2007;7:461–466.
  • Jokanović M. Structure-activity relationship and efficacy of pyridinium oximes in the treatment of poisoning with organophosphorus compounds: a review of recent data. Curr Top Med Chem. 2012;12:1775–1789.
  • Kuca K, Pohanka M. Chemical warfare agents. Exs. 2010;100:543–558.
  • Korabecny J, Soukup O, Dolezal R, et al. From pyridinium-based to centrally active acetylcholinesterase reactivators. Mini Rev Med Chem. 2014;14:215–221.
  • Sharma R, Gupta B, Singh N, et al. Development and structural modifications of cholinesterase reactivators against chemical warfare agents in last decade: a review. Mini Rev Med Chem. 2015;15:58–72.
  • Gorecki L, Korabecny J, Musilek K, et al. SAR study to find optimal cholinesterase reactivator against organophosphorous nerve agents and pesticides. Arch Toxicol. 2016;90:2831–2859.
  • Soukup O, Jun D, Tobin G, et al. The summary on non-reactivation cholinergic properties of oxime reactivators: the interaction with muscarinic and nicotinic receptors. Arch Toxicol. 2013;87:711–719.
  • Worek F, Thiermann H, Szinicz L, et al. Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes. Biochem Pharmacol. 2004;68:2237–2248.
  • Winter M, Wille T, Musilek K, et al. Investigation of the reactivation kinetics of a large series of bispyridinium oximes with organophosphate-inhibited human acetylcholinesterase. Toxicol Lett. 2016;244:136–142.
  • De Jong LP, Verhagen MA, Langenberg JP, et al. The bispyridinium-dioxime HLö-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman. Biochem Pharmacol. 1989;38:633–640.
  • Dolezal R, Korabecny J, Malinak D, et al. Ligand-based 3D QSAR analysis of reactivation potency of mono- and bis-pyridinium aldoximes toward VX-inhibited rat acetylcholinesterase. J Mol Graph Model. 2015;56:113–129.
  • Sakurada K, Matsubara K, Shimizu K, et al. Pralidoxime iodide (2-pAM) penetrates across the blood-brain barrier. Neurochem Res. 2003;28:1401–1407.
  • Karasova JZ, Chladek J, Hroch M, et al. Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and newly synthesized oxime K027, in rat plasma. J Appl Toxicol JAT. 2013;33:18–23.
  • Sit RK, Radić Z, Gerardi V, et al. New structural scaffolds for centrally acting oxime reactivators of phosphylated cholinesterases. J Biol Chem. 2011;286:19422–19430.
  • Radić Z, Sit RK, Kovarik Z, et al. Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases. J Biol Chem. 2012;287:11798–11809.
  • Pang YP, Quiram P, Jelacic T, et al. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. steps toward novel drugs for treating Alzheimer’s disease. J Biol Chem. 1996;271:23646–23649.
  • Nepovimova E, Korabecny J, Dolezal R, et al. 7-Methoxytacrine – 4-pyridinealdoxime hybrid as novel prophylactic agent with reactivation properties in organophosphate intoxications. Toxicol. Res. [Internet]. 2016. [cited 2016 May 30]; Available from: http://pubs.rsc.org/en/content/articlelanding/2016/tx/c6tx00130k.
  • Topczewski JJ, Quinn DM. Kinetic assessment of N-methyl-2-methoxypyridinium species as phosphonate anion methylating agents. Org Lett. 2013;15:1084–1087.
  • Soukup O, Kristofikova Z, Jun D, et al. The interaction of standard oxime reactivators with hemicholinium-3 sensitive choline carriers. Toxicol Lett. 2012;212:315–319.
  • Sepsova V, Krusek J, Zdarova Karasova J, et al. The interaction of quaternary reversible acetylcholinesterase inhibitors with the nicotinic receptor. Physiol Res Acad Sci Bohemoslov. 2014;63:771–777.
  • van Helden HP, Busker RW, Melchers BP, et al. Pharmacological effects of oximes: how relevant are they? Arch Toxicol. 1996;70:779–786.
  • Palu AK, West B, Zhou BN, et al., inventor; Morinda, INC, assignee. Methods and compositions for reactivating acetylcholinesterase. World Intellectual Property Organization WO 2005/086834. 2007 Sept 22
  • Dixon H, McDonough JA, Cabell LA, et al., inventor; Southwest research institute (US), assignee. ‘Bis-Quaternary Pyridinium-Aldoxime Salts and Treatment of Exposure to Cholinesterase Inhibitors. United States patent US 8,722,706. 2010 May 13
  • Cabell LA, McDonough JA, inventor; Southwest Research Institute (US), assignee. Two phase bioactive formulations. World Intellectual Property Organization WO 2009/114298. 2009 Sept 17
  • Chambers JE, Chambers HW, Meek EC, inventor; Mississippi state university, assignee. Phenoxyalkyl pyridinium oxime therapeutics for treatment of organophosphate poisoning. World Intellectual Property Organization WO 2011/142826. 2011 Nov 17
  • Chambers JE, Chambers HW, Meek EC, et al. Testing of novel brain-penetrating oxime reactivators of acetylcholinesterase inhibited by nerve agent surrogates. Chem Biol Interact. 2013;203:135–138.
  • Chambers JE, Meek EC, Bennett JP, et al. Novel substituted phenoxyalkyl pyridinium oximes enhance survival and attenuate seizure-like behavior of rats receiving lethal levels of nerve agent surrogates. Toxicology. 2016;339:51–57.
  • Chambers JE, Meek EC, Chambers HW. Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates. Ann N Y Acad Sci. 2016;1374:52–58.
  • Chambers JE, Chambers HW, Funck KE, et al. Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX. Chem Biol Interact. 2016;259:154–159.
  • McHardy SF, Corbett RM, Maxwell DM, et al., inventor; Southwest research institute (US), assignee. Oximes for treatment of peripheral and central nervous system exposure to acetyl cholinesterase inhibitors. United States patent US Citation2014/0066421. 2014 Mar 6
  • McHardy SF, Corbett RM, Maxwell DM, et al., inventor; Southwest research institute (US), assignee. Oximes for treatment of peripheral and central nervous system exposure to acetyl cholinesterase inhibitors. United States patent US 9,169,220. 2015 Oct 27.
  • Cashman JR, Kalisiak J, inventor; Human Biomolecular Research Institute, assignee. Blood brain barrier-penetrating oximes for cholistenerases reactivation. World Intellectual Property Organization WO 2012/083261. 2012 Jun 21
  • Skovira JW, O’Donnell JC, Koplovitz I, et al. Reactivation of brain acetylcholinesterase by monoisonitrosoacetone increases the therapeutic efficacy against nerve agents in guinea pigs. Chem Biol Interact. 2010;187:318–324.
  • Shih T-M, Skovira JW, O’Donnell JC, et al. Treatment with tertiary oximes prevents seizures and improves survival following sarin intoxication. J Mol Neurosci. 2010;40:63–69.
  • Bauta WT, Cantrell WR, Tidwell MW, inventor; Southwest research institute (US), assignee. Reactivators of organophosphorous inhibited acetylcholinesterase. United States patent US 9,162,983. 2015 Oct 20
  • Taylor P, Radic Z, Sharpless KB, et al., inventor; The Reagents of the University of California, The Scripps Research Institute, assignees. Centrally active and orally bioavailable antidotes for organophosphate exposure and methods for making and using them. World Intellectual Property Organization WO 2014/127315. 2014 Aug 21
  • Baati R, Kliachyna M, Baum V, et al., inventor; Universite de Strasbourg, Commissariat a l’energie atomique et aux energies alternatives, Centre National de la Recherche Scientifique, Universite de Rouen, L’etat Francais Represénté par le Directeur de l’institut de recherché biomédicale des armées, assignees. Novel uncharged reactivators against Op-inhibition of human acetylcholinesterase. World Intellectual Property Organization WO 2015/075082. 2015 May 28
  • Korabecny J, Holas O, Musilek K, et al. Synthesis and In Vitro Evaluation of New Tacrine Derivates-Bis-Alkylene Linked 7-MEOTA. Lett Org Chem. 2010;7:327–331.
  • Quinn DM, Topczewski JJ, inventor; University of Iowa Research Foundation, assignee. Compounds and methods to treat organophosphorus poisoning. United States patent US 9,249,100. 2016 Feb 2
  • Briseño-Roa L, Hill J, Notman S, et al. Analogues with fluorescent leaving groups for screening and selection of enzymes that efficiently hydrolyze organophosphorus nerve agents. J Med Chem. 2006;49:246–255.
  • Nachon F, Brazzolotto X, Trovaslet M, et al. Progress in the development of enzyme-based nerve agent bioscavengers. Chem Biol Interact. 2013;206:536–544.
  • Trovaslet-Leroy M, Musilova L, Renault F, et al. Organophosphate hydrolases as catalytic bioscavengers of organophosphorus nerve agents. Toxicol Lett. 2011;206:14–23.
  • Jacquet P, Daudé D, Bzdrenga J, et al. Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes. Environ Sci Pollut Res Int. 2016;23:8200–8218.
  • Taylor P, Radic Z, Fokin V, inventor; The Reagents of the University of California, The Scripps Research Institute, assignees. The catalytic scavengers of organophosphates to potentiate butyrylcholinesterase (BChE) as a catalytic bioscavenger and methods for making and using them. World Intellectual Property Organization WO 2015/057822. 2015 April 23
  • Radić Z, Dale T, Kovarik Z, et al. Catalytic detoxification of nerve agent and pesticide organophosphates by butyrylcholinesterase assisted with non-pyridinium oximes. Biochem J. 2013;450:231–242.
  • Robertson DE, Richardson T, Kustedjo K, et al., inventor; Verenium Corporation, Agentase LLC, Life Science Research Israel LTD., assignee; Enzymes and formulations for broad-specificity decontamination of chemical and biological warfare agents. World Intellectual Property Organization WO 2008/03061. 2008 March 27
  • Bajgar J Nerve agents poisoning and its treatment in schematic figures and tables [Internet]. Amsterdam: Elsevier; 2012. [cited 2016 Jan 4]. Available from: http://site.ebrary.com/id/10540384.
  • Papadopoulos V, Lecanu L, Greeson J, inventor; Samaritan Pharmaceuticals inc., Georgetown University, assignee. Antidotes to exogenous neurotoxic agents. World Intellectual Property Organization WO 2007/092458. 2007 Aug 16
  • Thompson C, Bharate S, inventor; The University of Montana, assignee. Benzothiazole-based pyridinium compounds for the treatment of neurodegenerative diseases or nerve agent exposure. United States patent US 9,255,091. 2016 Feb 9
  • Zemek F, Drtinova L, Nepovimova E, et al. Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf. 2014;13:759–774.
  • Black RM, Read RW. Biological markers of exposure to organophosphorus nerve agents. Arch Toxicol. 2013;87:421–437.
  • Seto Y, Kanamori-Kataoka M, Tsuge K, et al. Development of an on-site detection method for chemical and biological warfare agents. Toxin Rev. 2007;26:299–312.
  • Marrazza G. Piezoelectric biosensors for organophosphate and carbamate pesticides: a review. Biosensors. 2014;4:301–317.
  • Kim JH, Stevens RC, MacCoss MJ, et al. Identification and characterization of biomarkers of organophosphorus exposures in humans. Adv Exp Med Biol. 2010;660:61–71.
  • Loke WK, Tan YT, Seow J, invetor; DSO National Laboratories, assignee. Rapid detection of cholinesterase inhibitors. World Intellectual Property Organization WO 2008/066495. 2008 Jun 5
  • Walt DR, Bencic-Nagale S, inventor; Trustees of Tufts college, assignee. Chemical switches for detecting reactive chemical agents. World Intellectual Property Organization WO 2008/048698. 2008 Apr 24
  • Tazawa H, Ebata T, Takadera T, et al., inventor; Institute of Microchemical Technology Co. Ltd., Kansai Paint Co. Ltd., assignee. Cholinesterase-inhibitory material detecting device, detecting kit and detecting method. United States patent US 8,329,454. 2012 Dec 11
  • Redinbo MR, Hemmert AC, Edwards JS, inventor; The University of North Caroline at Chapel Hill, assignee. Methods and compositions for detection and identification of organophosphorus nerve agents, pesticides and other toxins. World Intellectual Property Organization WO 2011/072007. 2011 Jun 16
  • Marsillach J, Costa LG, Furlong CE. Protein adducts as biomarkers of exposure to organophosphorus compounds. Toxicology. 2013;307:46–54.
  • Musilek K, Jun D, Cabal J, et al. 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.
  • Kuca K, Bielavský J, Cabal J, et al. Synthesis of a new reactivator of tabun-inhibited acetylcholinesterase. Bioorg Med Chem Lett. 2003;13:3545–3547.
  • Calas A-G, Dias J, Rousseau C, et al. An easy method for the determination of active concentrations of cholinesterase reactivators in blood samples: application to the efficacy assessment of non quaternary reactivators compared to HI-6 and pralidoxime in VX-poisoned mice. Chem Biol Interact. 2016;267:11–16.
  • Worek F, Thiermann H. The value of novel oximes for treatment of poisoning by organophosphorus compounds. Pharmacol Ther. 2013;139:249–259.
  • Rosman Y, Eisenkraft A, Milk N, et al. Lessons learned from the Syrian sarin attack: evaluation of a clinical syndrome through social media. Ann Intern Med. 2014;160:644–648.

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