Brominated oxime nucleophiles are efficiently reactivating cholinesterases inhibited by nerve agents.
Cholinesterase
Nerve agent
Nucleophile
Organophosphate
Oxime
Reactivation
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
24 May 2024
24 May 2024
Historique:
received:
17
01
2024
accepted:
15
05
2024
medline:
25
5
2024
pubmed:
25
5
2024
entrez:
24
5
2024
Statut:
aheadofprint
Résumé
Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pK
Identifiants
pubmed: 38789714
doi: 10.1007/s00204-024-03791-6
pii: 10.1007/s00204-024-03791-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Grantová Agentura České Republiky
ID : GA21-03000S
Organisme : Univerzita Hradec Králové
ID : SV2112-2023
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Arnett EM, Reich R (1980) Electronic effects on the Menshutkin reaction. A complete kinetic and thermodynamic dissection of alkyl transfer to 3- and 4-substituted pyridines. J Am Chem Soc 102:5892–5902. https://doi.org/10.1021/ja00538a031
doi: 10.1021/ja00538a031
Bajgar J (2004) Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. In: Advances in Clinical Chemistry. Elsevier, pp 151–216
Čadež T, Kolić D, Šinko G, Kovarik Z (2021) Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase. Sci Rep 11:21486. https://doi.org/10.1038/s41598-021-00953-9
doi: 10.1038/s41598-021-00953-9
pubmed: 34728713
pmcid: 8563940
Carletti E, Colletier J-P, Dupeux F et al (2010) Structural evidence that human acetylcholinesterase inhibited by tabun ages through o-dealkylation. J Med Chem 53:4002–4008. https://doi.org/10.1021/jm901853b
doi: 10.1021/jm901853b
pubmed: 20408548
Clayden J, Greeves N, Warren S (2012) Organic chemistry, 2nd edn. OUP Oxford
doi: 10.1093/hesc/9780199270293.001.0001
Eichler T, Hauptmann S (2003) The chemistry of heterocycles: structures, reactions, synthesis, and applications, Wiley-VCH Verag GmbH&Co. KGaA
Ellman GL, Courtney KD, Andres V, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9
doi: 10.1016/0006-2952(61)90145-9
pubmed: 13726518
Franjesevic AJ, Sillart SB, Beck JM et al (2019) Resurrection and reactivation of acetylcholinesterase and butyrylcholinesterase. Chem Eur J 25:5337–5371. https://doi.org/10.1002/chem.201805075
doi: 10.1002/chem.201805075
pubmed: 30444932
Gorecki L, Andrys R, Schmidt M et al (2020) Cysteine-targeted insecticides against A. gambiae acetylcholinesterase are neither selective nor reversible inhibitors. ACS Med Chem Lett 11:65–71. https://doi.org/10.1021/acsmedchemlett.9b00477
doi: 10.1021/acsmedchemlett.9b00477
pubmed: 31938465
Gupta R (2015) Handbook of toxicology of chemical warfare agents, 2nd edn. Academic Press Elsevier, Amsterdam
Gupta B, Sharma R, Singh N et al (2013) In vitro reactivation kinetics of paraoxon- and DFP-inhibited electric eel AChE using mono- and bis-pyridinium oximes. Arch Toxicol https://doi.org/10.1007/s00204-013-1136-z
doi: 10.1007/s00204-013-1136-z
pubmed: 24065055
Howes L (2020) Novichok compound poisoned Navalny. C&EN Global Enterp 98:5–5. https://doi.org/10.1021/cen-09835-scicon3
doi: 10.1021/cen-09835-scicon3
John H, van der Schans MJ, Koller M et al (2018) Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network. Forensic Toxicol 36:61–71. https://doi.org/10.1007/s11419-017-0376-7
doi: 10.1007/s11419-017-0376-7
pubmed: 29367863
Karasova JZ, Zemek F, Bajgar J et al (2011) Partition of bispyridinium oximes (trimedoxime and K074) administered in therapeutic doses into different parts of the rat brain. J Pharm Biomed Anal 54:1082–1087. https://doi.org/10.1016/j.jpba.2010.11.024
doi: 10.1016/j.jpba.2010.11.024
pubmed: 21146949
Karasova J, Zemek F, Musilek K, Kuca K (2012) Time-dependent changes of oxime K027 concentrations in different parts of rat central nervous system. Neurotox Res https://doi.org/10.1007/s12640-012-9329-4
doi: 10.1007/s12640-012-9329-4
pubmed: 22585538
Karasova JZ, Kvetina J, Tacheci I et al (2017a) Pharmacokinetic profile of promising acetylcholinesterase reactivators K027 and K203 in experimental pigs. Toxicol Lett 273:20–25. https://doi.org/10.1016/j.toxlet.2017.03.017
doi: 10.1016/j.toxlet.2017.03.017
pubmed: 28343895
Karasova JZ, Maderycova Z, Tumova M et al (2017b) Activity of cholinesterases in a young and healthy middle-European population: relevance for toxicology, pharmacology and clinical praxis. Toxicol Lett 277:24–31. https://doi.org/10.1016/j.toxlet.2017.04.017
doi: 10.1016/j.toxlet.2017.04.017
pubmed: 28465191
Katalinić M, Maček Hrvat N, Žďárová Karasová J et al (2015) Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning. Arh Hig Rada Toksikol 66:291–298. https://doi.org/10.1515/aiht-2015-66-2740
doi: 10.1515/aiht-2015-66-2740
pubmed: 26751861
Kohoutova Z, Malinak D, Andrys R et al (2022) Charged pyridinium oximes with thiocarboxamide moiety are equally or less effective reactivators of organophosphate-inhibited cholinesterases compared to analogous carboxamides. J Enzyme Inhib Med Chem 37:760–767. https://doi.org/10.1080/14756366.2022.2041628
doi: 10.1080/14756366.2022.2041628
pubmed: 35193448
pmcid: 8881075
Kuca K, Bielavský J, Cabal J, Bielavská M (2003a) Synthesis of a potential reactivator of acetylcholinesterase—1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane bromide. Tetrahedron Lett 44:3123–3125. https://doi.org/10.1016/S0040-4039(03)00538-0
doi: 10.1016/S0040-4039(03)00538-0
Kuča K, Bielavský J, Cabal J, Kassa J (2003b) Synthesis of a new reactivator of tabun-inhibited acetylcholinesterase. Bioorg Med Chem Lett 13:3545–3547. https://doi.org/10.1016/S0960-894X(03)00751-0
doi: 10.1016/S0960-894X(03)00751-0
pubmed: 14505667
Kuca K, Jun D, Bajgar J (2007) Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro. Drug Chem Toxicol 30:31–40. https://doi.org/10.1080/01480540601017637
doi: 10.1080/01480540601017637
pubmed: 17364862
Lei C, Sun X (2018) Comparing lethal dose ratios using probit regression with arbitrary slopes. BMC Pharmacol Toxicol 19:61. https://doi.org/10.1186/s40360-018-0250-1
doi: 10.1186/s40360-018-0250-1
pubmed: 30290834
pmcid: 6173863
Meek E, Chambers H, Coban A et al (2012) Synthesis and in vitro and in vivo inhibition potencies of highly relevant nerve agent surrogates. Toxicol Sci 126:525–533. https://doi.org/10.1093/toxsci/kfs013
doi: 10.1093/toxsci/kfs013
pubmed: 22247004
Millard CB, Kryger G, Ordentlich A et al (1999) Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level. Biochemistry 38:7032–7039. https://doi.org/10.1021/bi982678l
doi: 10.1021/bi982678l
pubmed: 10353814
Misik J, Pavlikova R, Cabal J, Kuca K (2015) Acute toxicity of some nerve agents and pesticides in rats. Drug Chem Toxicol 38:32–36. https://doi.org/10.3109/01480545.2014.900070
doi: 10.3109/01480545.2014.900070
pubmed: 24641243
Misik J, Nepovimova E, Pejchal J et al (2018) Cholinesterase inhibitor 6-chlorotacrine—in vivo toxicological profile and behavioural effects. Curr Alzheimer Res 15:552–560. https://doi.org/10.3109/01480545.2014.900070
doi: 10.3109/01480545.2014.900070
pubmed: 29231138
Moshiri M, Darchini-Maragheh E, Balali-Mood M (2012) Advances in toxicology and medical treatment of chemical warfare nerve agents. Daru J Pharm Sci 20:81. https://doi.org/10.1186/2008-2231-20-81
doi: 10.1186/2008-2231-20-81
Musil K, Florianova V, Bucek P et al (2016) Development and validation of a FIA/UV–vis method for pKa determination of oxime based acetylcholinesterase reactivators. J Pharm Biomed Anal 117:240–246. https://doi.org/10.1016/j.jpba.2015.09.010
doi: 10.1016/j.jpba.2015.09.010
pubmed: 26386953
Musilek K, Jun D, Cabal J et al (2007) 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 50:5514–5518. https://doi.org/10.1021/jm070653r
doi: 10.1021/jm070653r
pubmed: 17924614
Musilek K, Malinak D, Nepovimova E et al (2020) Chapter 69—novel cholinesterase reactivators. In: Gupta RC (ed) Handbook of toxicology of chemical warfare agents, 3rd edn. Academic Press, Boston, pp 1161–1177
doi: 10.1016/B978-0-12-819090-6.00069-6
Nepovimova E, Kuca K (2018) Chemical warfare agent NOVICHOK—mini-review of available data. Food Chem Toxicol 121:343–350. https://doi.org/10.1016/j.fct.2018.09.015
doi: 10.1016/j.fct.2018.09.015
pubmed: 30213549
Pejchal J, Novotný J, Mařák V et al (2012) Activation of p38 MAPK and expression of TGF-β1 in rat colon enterocytes after whole body γ-irradiation. Int J Radiat Biol 88:348–358. https://doi.org/10.3109/09553002.2012.654044
doi: 10.3109/09553002.2012.654044
pubmed: 22233094
Quinn DM (1987) Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states. Chem Rev 87:955–979. https://doi.org/10.1021/cr00081a005
doi: 10.1021/cr00081a005
Saint-André G, Kliachyna M, Kodepelly S et al (2011) Design, synthesis and evaluation of new α-nucleophiles for the hydrolysis of organophosphorus nerve agents: application to the reactivation of phosphorylated acetylcholinesterase. Tetrahedron 67:6352–6361. https://doi.org/10.1016/j.tet.2011.05.130
doi: 10.1016/j.tet.2011.05.130
Sakurada K, Matsubara K, Shimizu K et al (2003) Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier. Neurochem Res 28:1401–1407. https://doi.org/10.1023/a:1024960819430
doi: 10.1023/a:1024960819430
pubmed: 12938863
Smith D, Anderson D, Degryse A-D et al (2018) Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report. Lab Anim 52:5–57. https://doi.org/10.1177/0023677217744587
doi: 10.1177/0023677217744587
pubmed: 29359995
pmcid: 5987990
Tallarida RJ, Murray RB (1986) Manual of pharmacologic calculations. Springer, New York
doi: 10.1007/978-1-4612-4974-0
Tambara K, Pantoş GD (2013) Conversion of aldoximes into nitriles and amides under mild conditions. Org Biomol Chem 11:2466–2472. https://doi.org/10.1039/C3OB27362H
doi: 10.1039/C3OB27362H
pubmed: 23429549
Tu AT (1999) Overview of sarin terrorist attacks in Japan. In: Natural and selected synthetic toxins. J Am Chem Soc pp 304–317. https://doi.org/10.1021/bk-2000-0745.ch020
Vanova N, Hojna A, Pejchal J et al (2021) Determination of K869, a novel oxime reactivator of acetylcholinesterase, in rat body fluids and tissues by liquid-chromatography methods: pharmacokinetic study. J Pharm Sci 110:1842–1852. https://doi.org/10.1016/j.xphs.2021.01.031
doi: 10.1016/j.xphs.2021.01.031
pubmed: 33545185
Vega JA, Vaquero JJ, Alvarez-Builla J et al (1999) A new approach to the synthesis of 2-aminoimidazo[1,2-a]pyridine derivatives through microwave-assisted N-alkylation of 2-halopyridines. Tetrahedron 55:2317–2326. https://doi.org/10.1016/S0040-4020(99)00012-5
doi: 10.1016/S0040-4020(99)00012-5
Watson A, Opresko D, Young RA et al (2015) Chapter 9—organophosphate nerve agents. In: Gupta RC (ed) Handbook of toxicology of chemical warfare agents, 2nd edn. Academic Press, Boston, pp 87–109
doi: 10.1016/B978-0-12-800159-2.00009-9
Worek F, Mast U, Kiderlen D et al (1999) Improved determination of acetylcholinesterase activity in human whole blood. Clin Chim Acta 288:73–90. https://doi.org/10.1016/S0009-8981(99)00144-8
doi: 10.1016/S0009-8981(99)00144-8
pubmed: 10529460
Worek F, Thiermann H, Szinicz L, Eyer P (2004) Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes. Biochem Pharmacol 68:2237–2248. https://doi.org/10.1016/j.bcp.2004.07.038
doi: 10.1016/j.bcp.2004.07.038
pubmed: 15498514
Worek F, von der Wellen J, Musilek K et al (2012) Reactivation kinetics of a homologous series of bispyridinium bis-oximes with nerve agent-inhibited human acetylcholinesterase. Arch Toxicol 86:1379–1386. https://doi.org/10.1007/s00204-012-0842-2
doi: 10.1007/s00204-012-0842-2
pubmed: 22437842
Žďárová Karasová J, Zemek F, Kassa J, Kuča K (2014) Entry of oxime K027 into the different parts of rat brain: comparison with obidoxime and oxime HI-6. J Appl Biomed 12:25–29. https://doi.org/10.1016/j.jab.2013.01.001
doi: 10.1016/j.jab.2013.01.001
Zdarova Karasova J, Hepnarova V, Andrys R et al (2020a) Encapsulation of oxime K027 into cucurbit[7]uril: in vivo evaluation of safety, absorption, brain distribution and reactivation effectiveness. Toxicol Lett 320:64–72. https://doi.org/10.1016/j.toxlet.2019.11.021
doi: 10.1016/j.toxlet.2019.11.021
pubmed: 31794810
Zdarova Karasova J, Mzik M, Kucera T et al (2020b) Interaction of Cucurbit[7]uril with oxime K027, atropine, and paraoxon: risky or advantageous delivery system? Int J Mol Sci 21:7883. https://doi.org/10.3390/ijms21217883
doi: 10.3390/ijms21217883
pubmed: 33114215
pmcid: 7672622
Zdarova Karasova J, Soukup O, Korabecny J et al (2021) Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats. Drug Chem Toxicol 44:207–214. https://doi.org/10.1080/01480545.2019.1566350
doi: 10.1080/01480545.2019.1566350
pubmed: 31257938
Zorbaz T, Malinak D, Maraković N et al (2018) Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physicochemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents. J Med Chem 61:10753–10766. https://doi.org/10.1021/acs.jmedchem.8b01398
doi: 10.1021/acs.jmedchem.8b01398
pubmed: 30383374
Zorbaz T, Malinak D, Hofmanova T et al (2022) Halogen substituents enhance oxime nucleophilicity for reactivation of cholinesterases inhibited by nerve agents. Eur J Med Chem 238:114377. https://doi.org/10.1016/j.ejmech.2022.114377
doi: 10.1016/j.ejmech.2022.114377
pubmed: 35526478