Synthesis and biological evaluation of novel N,N′-bis-methylenedioxybenzyl-alkylenediamines as bivalent anti-Alzheimer disease ligands

Figures & data

Scheme 1.  Reagent and condition: (i) Br₂, AcOH, rt, 1h; 95% (ii) NaOH, Cu, H₂O, reflux, 18h; 60% (iii) CH₂Br₂,CuO, K₂CO₃, DMF, 140°C, 4h; 70% (iv) MeOH, diamine, rt, 4h (v) NaBH₄, rt, 4h, 80–90%.

Table 1.  Inhibition activity of AChE and BuChE.

Compound	Chain length (n)	IC50 (µM)±SEM
		AChE^1	BuChE^2
5a	3	>125	52.31 ± 1.52
5b	4	119.96 ± 5.04	12.13 ± 0.51
5c	5	13.25 ± 1.19	3.35 ± 0.10
5d	6	9.78 ± 0.22	2.07 ± 0.11
5e	7	4.24 ± 0.08	3.02 ± 0.18
5f	8	2.79 ± 0.02	3.11 ± 0.06
5g	9	2.76 ± 0.02	5.14 ± 0.31
Rivastigmine		5.50 ± 1.50	1.60 ± 0.03

¹AChE from electric eel, IC₅₀, 50% inhibitory concentration (means ± SEM of three experiments) of AChE.

²BuChE from equine serum, IC₅₀, 50% inhibitory concentration (means ± SEM of three experiments) of BuChE.

Figure 1.  Lineweaver–Burk plot for the inhibition of acetylcholinesterase by 5g.

Figure 2.  Compounds 5a–5g Aβ_1-42 fibril inhibition compared with that of curcumin. The test was conducted in the presence of 20 μM compounds.

Table 2.  MTT assay of SH-SY5Y cell viability.

Compound	5a	5b	5c	5d	5e	5f	5g	Curcumin
Chain length (n)	3	4	5	6	7	8	9	-
IC50 (µM)	19.38	12.79	13.44	9.16	>50	>50	>50	40.00