Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker – Preparation and reactivation of tabun and paraoxon-inhibited

K Musilek; O Holas; D Jun; Francis James Gunn-Moore; V Dohnal; V Opletalova; M Dolezala; K Kuca

doi:10.1016/j.bmc.2007.08.002

Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker – Preparation and reactivation of tabun and paraoxon-inhibited

K Musilek, O Holas, D Jun, Francis James Gunn-Moore, V Dohnal, V Opletalova, M Dolezala, K Kuca

Research output: Contribution to journal › Article › peer-review

Abstract

Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Fifteen new monooxime reactivators of acetyleholinesterase with a (E)-but-2-ene linker were developed in an effort to extend the properties of K-oxime (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). The known reactivators (pralidoxime, HI-6, obidoxime, K075, K203) and the new compounds were tested in vitro on a model of tabun- and paraoxon-inhibited AChE. Monooxime reactivators were not able to exceed the best known compounds for tabun poisoning, but some of them did show reactivation comparable with known compounds for paraoxon poisoning. However, extensive differences were found by a SAR study for various substitutions on the non-oxime part of the reactivator molecule. (C) 2007 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	6733-6741
Number of pages	9
Journal	Bioorganic & Medicinal Chemistry
Volume	15
DOIs	https://doi.org/10.1016/j.bmc.2007.08.002
Publication status	Published - 1 Nov 2007

Keywords

acetylcholinesterase
reactivation
nerve agent
tabun pesticide
paraoxon
reactivator
oxime
BISPYRIDINIUM COMPOUNDS BEARING
PYRIDINIUM OXIMES
CHOLINESTERASE REACTIVATORS
CRYSTAL-STRUCTURES
SERIES
POTENCY
AGENT

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10.1016/j.bmc.2007.08.002

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@article{1962acfa8a13435a923f20c9aeef68cf,

title = "Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker – Preparation and reactivation of tabun and paraoxon-inhibited",

abstract = "Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Fifteen new monooxime reactivators of acetyleholinesterase with a (E)-but-2-ene linker were developed in an effort to extend the properties of K-oxime (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). The known reactivators (pralidoxime, HI-6, obidoxime, K075, K203) and the new compounds were tested in vitro on a model of tabun- and paraoxon-inhibited AChE. Monooxime reactivators were not able to exceed the best known compounds for tabun poisoning, but some of them did show reactivation comparable with known compounds for paraoxon poisoning. However, extensive differences were found by a SAR study for various substitutions on the non-oxime part of the reactivator molecule. (C) 2007 Elsevier Ltd. All rights reserved.",

keywords = "acetylcholinesterase, reactivation, nerve agent, tabun pesticide, paraoxon, reactivator, oxime, BISPYRIDINIUM COMPOUNDS BEARING, PYRIDINIUM OXIMES, CHOLINESTERASE REACTIVATORS, CRYSTAL-STRUCTURES, SERIES, POTENCY, AGENT",

author = "K Musilek and O Holas and D Jun and Gunn-Moore, {Francis James} and V Dohnal and V Opletalova and M Dolezala and K Kuca",

year = "2007",

month = nov,

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doi = "10.1016/j.bmc.2007.08.002",

language = "English",

volume = "15",

pages = "6733--6741",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier",

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AU - Musilek, K

AU - Holas, O

AU - Jun, D

AU - Gunn-Moore, Francis James

AU - Dohnal, V

AU - Opletalova, V

AU - Dolezala, M

AU - Kuca, K

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Fifteen new monooxime reactivators of acetyleholinesterase with a (E)-but-2-ene linker were developed in an effort to extend the properties of K-oxime (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). The known reactivators (pralidoxime, HI-6, obidoxime, K075, K203) and the new compounds were tested in vitro on a model of tabun- and paraoxon-inhibited AChE. Monooxime reactivators were not able to exceed the best known compounds for tabun poisoning, but some of them did show reactivation comparable with known compounds for paraoxon poisoning. However, extensive differences were found by a SAR study for various substitutions on the non-oxime part of the reactivator molecule. (C) 2007 Elsevier Ltd. All rights reserved.

AB - Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Fifteen new monooxime reactivators of acetyleholinesterase with a (E)-but-2-ene linker were developed in an effort to extend the properties of K-oxime (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). The known reactivators (pralidoxime, HI-6, obidoxime, K075, K203) and the new compounds were tested in vitro on a model of tabun- and paraoxon-inhibited AChE. Monooxime reactivators were not able to exceed the best known compounds for tabun poisoning, but some of them did show reactivation comparable with known compounds for paraoxon poisoning. However, extensive differences were found by a SAR study for various substitutions on the non-oxime part of the reactivator molecule. (C) 2007 Elsevier Ltd. All rights reserved.

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KW - tabun pesticide

KW - paraoxon

KW - reactivator

KW - oxime

KW - BISPYRIDINIUM COMPOUNDS BEARING

KW - PYRIDINIUM OXIMES

KW - CHOLINESTERASE REACTIVATORS

KW - CRYSTAL-STRUCTURES

KW - SERIES

KW - POTENCY

KW - AGENT

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DO - 10.1016/j.bmc.2007.08.002

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VL - 15

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EP - 6741

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

ER -

Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker – Preparation and reactivation of tabun and paraoxon-inhibited

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Keywords

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Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker – Preparation and reactivation of tabun and paraoxon-inhibited

Abstract

Keywords

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