Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

K Musilek; K Kuca; D Jun; V Dohnal; M Dolezal

doi:10.1080/14756360500179762

Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

J Enzyme Inhib Med Chem. 2005 Oct;20(5):409-15. doi: 10.1080/14756360500179762.

Authors

K Musilek¹, K Kuca, D Jun, V Dohnal, M Dolezal

Affiliation

¹ Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.

PMID: 16335048
DOI: 10.1080/14756360500179762

Abstract

Nine potential AChE reactivators were synthesized using a modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by insecticide chlorpyrifos was tested in vitro. 2,2'-Bis(hydroxyiminomethyl)-1,1'-(1,4-phenylenedimethyl)-bispyridinium dibromide seems to be the most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as length of the linking chain between both pyridinium rings and position of the oxime moiety on the pyridinium ring.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism*
Animals
Chlorpyrifos / pharmacology*
Cholinesterase Inhibitors / pharmacology*
Cross-Linking Reagents / chemistry*
Enzyme Activation / drug effects
Molecular Structure
Oximes / chemistry
Pyridinium Compounds / chemical synthesis*
Pyridinium Compounds / chemistry
Pyridinium Compounds / pharmacology*
Rats
Structure-Activity Relationship
Xylenes / chemistry*

Substances

Cholinesterase Inhibitors
Cross-Linking Reagents
Oximes
Pyridinium Compounds
Xylenes
Acetylcholinesterase
Chlorpyrifos