The preparation, in vitro screening and molecular docking of symmetrical bisquaternary cholinesterase inhibitors containing a but-(2E)-en-1,4-diyl connecting linkage

Figures & data

Figure 1.  Selected acetylcholinesterase inhibitors and reactivators.

Figure 2.  Prepared bisquaternary pyridinium salts.

Figure 3.  Docking results for compound 10 with hAChE.

Figure 4.  Penetration of compound 10 into the the hAChE active site gorge.

Table 1.  The IC₅₀ values of the tested compounds (a; no inhibition observed; b; not soluble in screening medium).

Compound	AChE IC50 ± SD (µM)	BChE IC50 ± SD (µM)	Ki1/Ki2 (µM)
pyridostigmine (1)	40 ± 7.8	16 000 ± 260.8	4.94/2.52
neostigmine(2)	0.1 ± 0.02	0.8 ± 0.13	0.44/0.07
pralidoxime (3)	878 ± 171	a	---
K203 (4)	566 ± 110	3 130 ± 510	---
5	0.9 ± 0.2	a	---
6	212 ± 41	850 ± 138	---
7	40 ± 8	169 ± 28	---
8	71 ± 14	18 ± 3	---
9	b	b	---
10	0.05 ± 0.01	22 ± 4	0.003/0.009
11	73 ± 14	18 ± 3	---
12	509 ± 99	a	---
13	799 ± 155	4 510 ± 735	---
14	54 ± 11	1 440 ± 234	---
15	1.2 ± 0.2	17 ± 3	---
16	189 ± 37	1 620 ± 264	---
17	139 ± 27	324 ± 53	---
18	3 870 ± 754	a	---
19	401 ± 78	a	---
20	1 200 ± 234	a	---
21	70 ± 14	514 ± 84	---