title: In vitro reactivation potency of novel symmetrical bis-pyridinium oximes for electric eel acetylcholinesterase inhibited by nerve agent sarin.
abstract: This communication describes synthesis and in vitro evaluation of 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 as reactivators of sarin inhibited acetylcholinesterase (AChE). The reactivation data of synthesized oximes were compared with those of 2-PAM and obidoxime. The efficacy of oximes such as 1,4-dimethoxy cis-but-2-ene bis-[4,4'-(hydroxyiminomethyl)-pyridinium] dichloride (3g), 1,4-dimethoxy benzene bis-[3,3'-(hydroxyimino-methyl) pyridinium] dichloride (3b) and 1,3-dimethoxy benzene bis-[3,3'-(hydroxy-iminomethyl) pyridinium] dichloride (3e) were found to be more than that of obidoxime in reactivating sarin inhibited AChE. The oxime 3g was able to reactivate 25% of AChE activity in comparison to 20% and 5% reactivation exhibited by 2-PAM and obidoxime respectively at a concentration of 10(-4) M. The pKa of the oximes were determined and correlated with the reactivation potential.
authors: Process Technology Development Division, Defence Research & Development Establishment, Jhansi Road, Gwalior 474 002, India. jracharya@rediffmail.com
authors: Jyotiranjan
authors: J
authors: Acharya
authors: Devendra Kumar
authors: DK
authors: Dubey
authors: M P
authors: MP
authors: Kaushik
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis / Q000737:chemistry*; D004593:Electrophorus; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D012524:Sarin / Q000737:chemistry*
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D012524:Sarin