Synthesis and in vitro evaluation of xylene linked carbamoyl bis-pyridinium monooximes as reactivators of organophosphorus (OP) inhibited electric eel acetylcholinesterase (AChE).

A series of carbamoyl bis-pyridinium monooximes linked with xylene linker were synthesized and their in-vitro reactivation potential was evaluated against acetylcholinesterase (AChE) inhibited by organophosphorus inhibitors (OP) such as sarin, DFP and VX and the data were compared with reactivation obtained with 2-PAM and obidoxime. Amongst the synthesized compounds, 3-carbamoyl-2'hydroxyiminomethyl-1-1'-(1,4-phenylenedimethyl)-bispyridinium dibromide (5e) 3-carbamoyl-2'hydroxyiminomethy l-1-1'-(1,3-phenylenedimethyl)-bispyridinium dibromide (5k) and 4-carbamoyl-2'hydroxyiminomethyl-1-1'-(1,3-phenylenedimethyl)-bispyridinium dibromide (5l) were found to be the most potent reactivators for electric eel AChE inhibited by sarin and DFP. However, in case of VX inhibited AChE, none of the synthesized oximes could surpass the reactivation potential of 2-PAM and obidoxime. The pKa values of all the oximes were determined and correlated with their observed reactivation potential.