Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase

Figures & data

Figure 1 Examples of organophosphorus compounds.

Figure 2 Currently used AChE reactivators.

Figure 3 Promising oximes tested on tabun-inhibited AChE.

Figure 4 Six oxime reactivators tested against tabun and paraoxon-inhibited AChE.

Scheme 1 Two step synthesis of monooxime-monocarbamoyl bisquaternary compounds with (E)-but-2-ene linker.

Table I.  Reactivation potencies of tested oximes.

	Reactivation (%)
Inhibitor	Tabun		Paraoxon
Reactivator/Concentration	10^− 3 M	10^− 5 M	10^− 3 M	10^− 5 M
K048 (1)	25 ± 0	0	57 ± 3	5 ± 2
K075 (2)	16 ± 1	23 ± 1	60 ± 1	46 ± 2
pralidoxime (3)	4 ± 1	0	42 ± 1	0
HI-6 (4)	2 ± 1	4 ± 1	35 ± 2	0
obidoxime (5)	11 ± 0	0	76 ± 2	37 ± 2
6	0	0	44 ± 1	39 ± 3
7	0	0	16 ± 0	0
8	55 ± 0	18 ± 0	64 ± 2	23 ± 1
9	0	0	18 ± 1	33 ± 3
10	0	0	0	25 ± 0
11	8 ± 0	5 ± 0	53 ± 0	49 ± 0

%, mean value of three independent determinations) – time of inhibition – 30 min; time of reactivation by AChE reactivators – 10 min; pH 7.6; temperature 25°C.