In vitro reactivation of sarin inhibited electric eel acetylcholinesterase by bis-pyridinium oximes bearing methoxy ether linkages.
Bis-pyridinium oximes connected by methoxy alkane ether linker were synthesized and their in vitro reactivation efficacy was evaluated for sarin inhibited AChE. Reactivation efficacy of synthesized compounds was compared with 2-PAM and obidoxime. Among the synthesized compounds, 1,2-dimethoxy ethylene bis-[3,3'-(hydroxyiminomethyl) pyridinium] dichloride (3P-2) and 1,3-dimethoxy propylene bis-[3,3'-(hydroxyiminomethyl) pyridinium] dichloride (3P-3) were found to be most potent reactivators for AChE inhibited by nerve agent sarin. 3P-2 and 3P-3, respectively exhibited 80% and 69% regeneration of inhibited AChE, whereas 2-PAM (well known antidote for nerve agent poisoning) showed 42% regeneration.
Acharya
Jyotiranjan
J
Process Technology Development Division, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India. jracharya@rediffmail.com
Gupta
Arvind Kumar
AK
Mazumder
Avik
A
Dubey
Devendra Kumar
DK
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D004593:Electrophorus / Q000502:physiology*; D009768:Obidoxime Chloride / Q000494:pharmacology; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D012524:Sarin / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D012524:Sarin; D000110:Acetylcholinesterase; C028797:pralidoxime