Synthesis and evaluation of novel bis-pyridinium oximes as reactivators of DFP-inhibited acetylcholinesterase.
A series of novel bis-pyridinium oximes connected by bis-methoxymethyl benzene, 1,4-bis-methoxymethyl (cis)-but-2-ene and 1,4-bis-methoxymethyl but-2-yne linkers were synthesized and their in vitro reactivation efficacy was evaluated against diisopropyl phosphorofluoridate (DFP) inhibited acetylcholinesterase (AChE) and compared with the established antidote 2-PAM and obidoxime. However, the best reactivation was observed with the standard oxime 2-PAM. The reactivation efficacy of 1,3-dimethoxymethyl benzene bis-[4,4'-(hydroxyiminomethyl) pyridinium] dichloride (3d) and 1,4-dimethoxy but-2-ene bis-[4,4'-(hydroxyiminomethyl) pyridinium] dichloride (3g) was comparable with that of obidoxime, another standard antidote.
Acharya
Jyotiranjan
J
Process Technology Development Division, Defence Research and Development Establishment, Jhansi Road, Gwalior, Madhya Pradesh 474002, India. jracharya@rediffmail.com
Gupta
Arvind Kumar
AK
Dubey
Devendra Kumar
DK
Raza
Syed Kalbey
SK
D000110:Acetylcholinesterase / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007531:Isoflurophate / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D007531:Isoflurophate; D000110:Acetylcholinesterase