Quaternary salts of 3,3'-bis-pyridinium monooximes: synthesis and biological activity

Two new series of asymetrically substituted 3,3'-bis-pyridinium monooximes bridged by oxopropane and propane groups were synthesized and characterized by spectral data and acid dissociation constants (pKas). Both the in vitro reactivation potency, in experiments with lyophilized electric eel acetylcholinesterase (AChE) inhibited by diisopropylfluorophosphate, and in vivo protection efficacy against diisopropylfluorophosphate intoxication in mice of these compounds were evaluated and compared with those of trimedoxime and 2-pyridine-aldoxime methiodide. The compounds were also evaluated for in vitro inhibition of AChE. The compounds with the oxopropane link were stronger inhibitors and weaker reactivators than the corresponding propane derivatives. No significant correlation was observed among pKa, oxime inhibition of AChE, reactivation of inhibited AChE, and protection index. Changing substituents in pyridine rings or altering linking groups between pyridine rings did not improve antidotal efficacy compared with trimedoxime and 2-pyridine-aldoxime methiodide.