Literature DB >> 31097996

Synthesis and Molecular Properties of Nerve Agent Reactivator HLö-7 Dimethanesulfonate.

Fu-Lian Hsu1, Su Y Bae1, Jack McGuire2, Dana R Anderson3, Stephanie M Bester2, Jude J Height1, Scott D Pegan1,2,3, Andrew J Walz1.   

Abstract

The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLö-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLö-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLö-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.

Entities:  

Year:  2019        PMID： 31097996      PMCID： PMC6511945          DOI： 10.1021/acsmedchemlett.9b00021

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  16 in total

1.  Reactivation of organophosphate-inhibited human acetylcholinesterase by isonitrosoacetone (MINA): a kinetic analysis.

Authors:  Franz Worek; Horst Thiermann
Journal:  Chem Biol Interact       Date:  2011-09-09       Impact factor: 5.192

Review 2.  Overcoming apathy in research on organophosphate poisoning.

Authors:  Nick A Buckley; Darren Roberts; Michael Eddleston
Journal:  BMJ       Date:  2004-11-20

3.  Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime: structural basis for differences in the ability to reactivate tabun conjugates.

Authors:  Fredrik Ekström; Yuan-Ping Pang; Malin Boman; Elisabet Artursson; Christine Akfur; Susanne Börjegren
Journal:  Biochem Pharmacol       Date:  2006-07-31       Impact factor: 5.858

4.  Muscle force and acetylcholinesterase activity in mouse hemidiaphragms exposed to paraoxon and treated by oximes in vitro.

Authors:  Horst Thiermann; Peter Eyer; Franz Worek
Journal:  Toxicology       Date:  2010-04-10       Impact factor: 4.221

5.  Effects of oximes on muscle force and acetylcholinesterase activity in isolated mouse hemidiaphragms exposed to paraoxon.

Authors:  Horst Thiermann; Peter Eyer; Franz Worek; Ladislaus Szinicz
Journal:  Toxicology       Date:  2005-07-22       Impact factor: 4.221

6.  A new H-oxime restores rat diaphragm contractility after esterase inhibition in vitro.

Authors:  P Alberts
Journal:  Eur J Pharmacol       Date:  1990-08-02       Impact factor: 4.432

7.  Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes.

Authors:  Franz Worek; Horst Thiermann; Ladislaus Szinicz; Peter Eyer
Journal:  Biochem Pharmacol       Date:  2004-12-01       Impact factor: 5.858

8.  HLö 7 dimethanesulfonate, a potent bispyridinium-dioxime against anticholinesterases.

Authors:  P Eyer; I Hagedorn; R Klimmek; P Lippstreu; M Löffler; H Oldiges; U Spöhrer; I Steidl; L Szinicz; F Worek
Journal:  Arch Toxicol       Date:  1992       Impact factor: 5.153

9.  Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes.

Authors:  F J Ekström; C Astot; Y-P Pang
Journal:  Clin Pharmacol Ther       Date:  2007-04-18       Impact factor: 6.875

10.  Structure of HI-6*sarin-acetylcholinesterase determined by X-ray crystallography and molecular dynamics simulation: reactivator mechanism and design.

Authors:  Fredrik Ekström; Andreas Hörnberg; Elisabet Artursson; Lars-Gunnar Hammarström; Gunter Schneider; Yuan-Ping Pang
Journal:  PLoS One       Date:  2009-06-18       Impact factor: 3.240
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  3 in total

Review 1.  Organophosphorus compounds and oximes: a critical review.

Authors:  Franz Worek; Horst Thiermann; Timo Wille
Journal:  Arch Toxicol       Date:  2020-06-06       Impact factor: 5.153

2.  Demystifying Chronic Kidney Disease of Unknown Etiology (CKDu): Computational Interaction Analysis of Pesticides and Metabolites with Vital Renal Enzymes.

Authors:  Harindu Rajapaksha; Dinesh R Pandithavidana; Jayangika N Dahanayake
Journal:  Biomolecules       Date:  2021-02-10

3.  CdTe QD-based inhibition and reactivation assay of acetylcholinesterase for the detection of organophosphorus pesticides.

Authors:  Jyoti Korram; Lakshita Dewangan; Indrapal Karbhal; Rekha Nagwanshi; Sandeep K Vaishanav; Kallol K Ghosh; Manmohan L Satnami
Journal:  RSC Adv       Date:  2020-06-25       Impact factor: 4.036
  3 in total

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