Targeted synthesis of 1-(4-hydroxyiminomethylpyridinium)-3-pyridiniumpropane dibromide--a new nerve agent reactivator
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
17960099
PubMed Central
PMC6149109
DOI
10.3390/12081964
PII: 12081964
Knihovny.cz E-zdroje
- MeSH
- acetylcholinesterasa MeSH
- lidé MeSH
- organofosfáty antagonisté a inhibitory MeSH
- organofosforové sloučeniny antagonisté a inhibitory MeSH
- oximy chemická syntéza MeSH
- pyridinové sloučeniny chemická syntéza MeSH
- reaktivátory cholinesterázy chemická syntéza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1-(4-hydroxyiminomethylpyridinium)-3-pyridiniumpropane MeSH Prohlížeč
- acetylcholinesterasa MeSH
- cyclohexyl methylphosphonofluoridate MeSH Prohlížeč
- organofosfáty MeSH
- organofosforové sloučeniny MeSH
- oximy MeSH
- pyridinové sloučeniny MeSH
- reaktivátory cholinesterázy MeSH
- tabun MeSH Prohlížeč
Preparation of 1-(4-hydroxy-iminomethylpyridinium)-3-pyridiniumpropane dibromide is described. This compound represents a new acetylcholinesterase (AChE) reactivator, which has no substituents on the second pyridinium ring as found in other commonly used AChE reactivators. The reactivation ability of this reactivator was tested on tabun- and cyclosarin-inhibited AChE. According to the results obtained, the new compound (without substitution and with decreased molecule size) showed increased reactivation potency in case of cyclosarin inhibited AChE. A potent oxime for treatment of tabun and cyclosarin-caused intoxications was thus obtained via slight modification of the reactivator structure (compared to trimedoxime and K027).
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Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv. Clin. Chem. 2004;38:151–216. PubMed
Tu A.T. Chemical Terrorism: Horrors in Tokyo Subway and Matsumoto City. Alaken Inc.; Fort Collins, CO: 2002.
Matousek J. Health and environmental threats associated with the destruction of chemical weapons. Ann. N. Y. Acad. Sci. 2006;1076:549–558. PubMed
Poziomek E.J., Hackley B.E., Steinberg G.M. J. Pyridinium aldoximes. J. Org. Chem. 1958;23:714–717.
Lüttringhaus 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. PubMed
Hagedorn I., Gündel W.H., Schoene K. Reactivation of phosphorylated acetylcholine esterase with oximes: contribution to the study of the reaction course. Arzneimittelforschung. 1969;19:603–606. PubMed
Krejcova G., Kuca K., Sevelova L. Cyclosarin-An Organophosphate Nerve Agent. Def. Sci. J. 2005;55:105–115.
Musilek K., Kuca K., Jun D., Dolezal M. Progress in synthesis of new acetylcholinesterase reactivators in period 1990-2004. Curr. Org. Chem. 2007;11:229–238.
Musilek K., Lipka L., Racakova V., Kuca K., Jun D., Dohnal V., Dolezal M. New methods in synthesis of acetylcholinesterase reactivators and evaluation of their potency to reactivate cyclosarin-inhibited AChE. Chem. Pap. 2006;60:48–51. doi: 10.2478/s11696-006-0008-x. DOI
Eyer P., Szinicz L., Thiermann H., Worek F., Zilker T. Testing of antidotes for organophosphorus compounds: Experimental procedures and clinical reality. Toxicology. 2007;233:108–119. PubMed
Kuca K., Cabal J., Musilek K., Jun D., Bajgar J. Effective bisquaternary reactivators of tabun-inhibited AChE. J. Appl. Toxicol. 2005;25:491–495. PubMed
Szinicz L., Worek F., Thiermann H., Kehe K., Eckert S., Eyer P. Development of antidotes: Problems and strategies. Toxicology. 2007;233:23–30. PubMed
Yang G.Y., Yoon J.H., Seong C.M., Park N.S., Jung Y.S. Synthesis of bis-pyridinium oxime antidotes using bis(methylsulfonoxymethyl) ether for organophosphate nerve agents. Bull. Korean Chem. Soc. 2003;24:1368–1370. doi: 10.5012/bkcs.2003.24.9.1368. DOI
Park N.-J., Jung Y.-S., Musilek K., Jun D., Kuca K. Potency of several structurally different acetylcholinesterase reactivators to reactivate house fly and bovine acetylcholinesterases inhibited by paraoxon and DFP. B. Korean Chem. Soc. 2006;27:1401–1404. doi: 10.5012/bkcs.2006.27.9.1401. DOI
Chennamaneni S.R., Vobalaboina V., Garlapati A. Quaternary salts of 4,3' and 4,4' bis-pyridinium monooximes: synthesis and biological activity. Bioorg. Med. Chem. Lett. 2005;15:3076–3080. doi: 10.1016/j.bmcl.2005.04.026. PubMed DOI
Srinivas Rao C., Venkateswarlu V., Achaiah G. Quaternary salts of 4,3' and 4,4' bis-pyridinium monooximes. Part 2: synthesis and biological activity. Bioorg. Med. Chem. Lett. 2006;16:2134–2138. PubMed
Musilek K., Kuca K., Jun D., Dohnal V., Dolezal M. Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase. J. Enzym. Inhib. Med. Chem. 2005;20:409–415. doi: 10.1080/14756360500179762. PubMed DOI
Musilek K., Kuca K., Jun D., Dohnal V., Dolezal M. Synthesis of the novel series of bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase. Bioorg. Med. Chem. Lett. 2006;16:622–627. doi: 10.1016/j.bmcl.2005.10.059. PubMed DOI
Musilek K., Holas O., Kuca K., Jun D., Dohnal V., Dolezal M. Synthesis of asymmetrical bispyridinium compounds bearing cyano-moiety and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. Bioorg. Med. Chem. Lett. 2006;16:5673–5676. doi: 10.1016/j.bmcl.2006.08.011. PubMed DOI
Musilek K., Holas O., Kuca K., Jun D., Dohnal V., Opletalova V., Dolezal M. Novel series of bispyridinium compounds bearing a (Z)-but-2-ene Linker – Synthesis and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. Bioorg. Med. Chem. Lett. 2007;17:3172–3176. PubMed
Oh K.A., Yang G.Y., Jun D., Kuca K., Jung Y.S. Bis-pyridiumaldoxime reactivators connected with CH2O(CH2)n OCH2 linkers between pyridinium rings and their reactivity against VX. Biorg. Med. Chem. Lett. 2006;16:4852. doi: 10.1016/j.bmcl.2006.06.063. PubMed DOI
Odzak R., Calic M., Hrenar T., Primozic I., Kovarik Z. Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase. Toxicology. 2007;233:85–96. doi: 10.1016/j.tox.2006.08.003. PubMed DOI
Kuca K., Bielavsky J., Cabal J., Bielavska M. Synthesis of a potential reactivator of acetylcholinesterase-1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium)-propane dibromide. Tetrahedron Lett. 2003;44:3123–3125.
Kuca K., Kassa J. In vitro reactivation of acetylcholinesterase using the oxime K027. Vet. Hum. Toxicol. 2004;46:15–18. PubMed
Calic M., Lucic Vrdoljak A., Radic B., Jelic D., Jun D., Kuca K., Kovarik Z. In vitro and in vivo evaluation of pyridinium oximes: mode of interaction with acetylcholinesterase, effect on tabun- and soman-poisoned mice and their cytotoxicity. Toxicology. 2006;219:85–96. PubMed
Lucic-Vrdoljak A., Calic M., Radic B., Berend S., Kuca K., Kovarik Z. Pretreatment with pyridinium oximes improves antidotal therapy against tabun poisoning. Toxicology. 2006;228:41–50. PubMed
Kassa J., Kuca K., Cabal J., Paar M. A comparison of the efficacy of new asymmetric bispyridinium oximes (K027, K048) with currently available oximes against tabun by in vivo methods. J. Toxicol. Environ. Health A. 2006;69:1875–1882. PubMed
Kuca K., Cabal J., Jun D., Bajgar J., Hrabinova M. Potency of new structurally different oximes to reactivate cyclosarin inhibited-human brain acetylcholinesterases. J. Enzyme Inhib. Med. Chem. 2006;21:6636–666. doi: 10.1080/14756360600850916. PubMed DOI
Musilek K., Kuca K., Jun D., Dolezal M. Synthesis of bispyridinium compounds bearing propane linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase. Lett. Org. Chem. 2006;3:831–835. PubMed
Kuca K., Cabal J. Evaluation of newly synthesized reactivators of the brain cholinesterase inhibited by sarin nerve agent. Toxicol. Mech. Meth. 2005;15:247–252. PubMed
Bajgar J., Fusek J., Kuca K., Bartosova L., Jun D. Treatment of organophosphate intoxication using cholinesterase reactivators: facts and fiction. Mini-Rev. Med. Chem. 2007;7:461–466. PubMed
Kuca K., Jun D., Musilek K. Structural requirements of acetylcholinesterase reactivators. Mini-Rev. Med. Chem. 2006;6:269–277. PubMed
Kuca K., Jun D., Musilek K., Bajgar J. Reactivators of tabun-Inhibited tcetylcholinesterase: Structure biological activity relationship. Front. Drug Des. Discov. 2007;3:381–394.
Ekstrom F., Akfur C., Tunemalm A.K., Lundberg S. Structural changes of phenylalanine 338 and histidine 447 revealed by the crystal structures of tabun-inhibited murine acetylcholinesterase. Biochemistry. 2006;45:74–81. PubMed
Ekstrom F., Pang Y.P., Boman M., Artursson E., Akfur C., Borjegren 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. PubMed