In vitro reactivation of sarin-inhibited human acetylcholinesterase (AChE) by bis-pyridinium oximes connected by xylene linkers.

A series of bis-pyridinium oximes connected by xylene linkers were synthesized and their in vitro reactivation potential was evaluated against human acetylcholinesterase (hAChE) inhibited by nerve agent sarin and the data were compared with 2-PAM and obidoxime. Among the synthesized compounds, N,N'-p-xylene-bis-[(2,2'-hydroxyiminomethyl)pyridinium] dibromide (3c) was found to be the most potent reactivator for hAChE inhibited by sarin. The oxime 3c exhibited 45% regeneration of inhibited hAChE, in comparison to 34% and 24% regeneration by 2-PAM and obidoxime, respectively, at a concentration of 10(-3) M within 10 min.

In vitro evaluation of bis-pyridinium oximes bearing methoxy alkane linker as reactivators of sarin inhibited human acetylcholinesterase.

A series of bis-pyridinium oximes connected by methoxy alkane linkers were synthesized and their in vitro reactivation efficacy was evaluated against sarin-inhibited human AChE, and data were compared with 2-PAM and obidoxime. Among the synthesized compounds, 1,2-dimethoxy ethylene bis-[4,4'-(hydroxyiminomethyl) pyridinium] dichloride (4P-2) and 1,2-dimethoxy ethylene bis-[3,3'-(hydroxyiminomethyl) pyridinium] dichloride (3P-2) were found to be the most potent reactivators of human AChE inhibited by nerve agent sarin. The oximes 4P-2 and 3P-2 exhibited 41% and 36% regeneration of sarin-inhibited AChE, respectively, whereas 2-PAM showed 32% regeneration.

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.