Reactivation potency of fluorinated pyridinium oximes for acetylcholinesterases inhibited by paraoxon organophosphorus agent.
For the purpose of developing new oxime reactivators of acetylcholinesterases (AChE) that have been inhibited by organophosphorus agents, emphasis was given to the finding that the lipophilic nature of fluorinated compounds is responsible for their enhanced transport across the blood brain barrier (BBB). As a result, we have designed and synthesized the fluorinated oxime derivatives, which quantum mechanical calculations suggest should have a greater lipophilicity and BBB permeability than their non-fluorinated analogs. Among the compounds explored in this study, 4 was found to have the highest potency for reactivation of paraoxon-inhibited housefly (HF) AChE.
Jeong
Hee Chun
HC
Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong, Daejeon 305-600, Republic of Korea.
Kang
Nam Sook
NS
Park
No-Joong
NJ
Yum
Eul Kyun
EK
Jung
Young-Sik
YS
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006793:Houseflies / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D010261:Paraoxon / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D010091:Oximes; D010261:Paraoxon