Synthesis of a novel series of non-symmetrical bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase

Figures & data

Scheme 1 AChE inhibited by nerve agent tabun.

Scheme 2 Oxime induced reactivation of tabun-inhibited AChE.

Figure 1 Examples of oxime reactivators currently used against OP intoxications.

Scheme 3 Potential oxime reactivators tested against tabun- and paraoxon-inhibited AChE.

Scheme 4 Two step synthesis of non-symmetrical bisquaternary compounds.

Table I.  Reactivation potencies of tested oximes (%, mean value of three independent determinations) – time of inhibition – 30 min; time of reactivation by AChE reactivators – 10 min; pH 8; temperature 25°C.

	Reactivation (%)
Inhibitor	Tabun		Paraoxon
Reactivator/Concentration	10^− 3 M	10^− 5 M	10^− 3 M	10^− 5 M
pralidoxime (1)	4 ± 1	0	42 ± 1	0
HI-6 (2)	2 ± 1	4 ± 1	35 ± 2	0
obidoxime (3)	11 ± 0	0	76 ± 2	37 ± 2
4	0	0	0	0
5	0	0	0	0
6	0	0	0	0
7	0	0	0	49 ± 4
8	0	0	0	53 ± 3
9	0	0	0	0
10	0	0	0	46 ± 1
11	0	0	0	53 ± 6
12	0	0	0	0
13	0	6 ± 2	0	5 ± 0
14	0	0	3 ± 0	0
15	0	3 ± 1	44 ± 0	17 ± 0
16	0	13 ± 2	12 ± 0	65 ± 0
17	0	0	8 ± 0	6 ± 0
18	0	10 ± 1	7 ± 2	51 ± 1
19	0	19 ± 2	0	63 ± 0
20	0	3 ± 1	0	8 ± 0
21	0	7 ± 1	0	27 ± 1