Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents

Figures & data

Scheme 1. General synthetic route to 3-arylcoumarin, reagents, and conditions: (a) sulphur, p-toluenesulfonic acid, morpholine, 120 °C; (b) sodium hydroxide solution, tetrabutylammonium bromide, 100 °C; (c) acetic anhydride, triethylamine, 112 °C.

Table 1. Compounds 1–24.

Product	R1	R2	R3	R4	R5	R6	R7	R8
1	H	H	H	H	H	OH	H	H
2	H	H	H	H	OH	H	H	H
3	H	H	H	H	OH	OH	H	H
4	H	H	OH	H	H	OH	H	H
5	H	H	OH	H	H	H	H	H
6	H	H	OH	H	OH	H	H	H
7	H	H	OH	H	H	OH	H	OH
8	H	H	OH	H	OH	OH	H	H
9	H	H	OH	H	H	OCH3	H	H
10	H	H	OH	H	H	H	OCH3	H
11	H	H	OH	H	H	H	OH	H
12	H	H	OCH3	OCH3	OH	OH	H	H
13	H	H	OCH3	H	H	OH	H	H
14	H	H	OCH3	H	OH	H	H	H
15	H	H	OCH3	H	OH	OH	H	H
16	H	H	CH3	H	H	OH	H	H
17	H	H	CH3	H	OH	OH	H	H
18	H	H	F	H	H	OH	H	H
19	H	H	F	H	OH	OH	H	H
20	H	H	Br	H	H	H	H	H
21	H	H	Br	H	OH	OH	H	H
22	H	H	OH	OH	OH	OH	H	H
23	CH3	H	H	CH3	OH	OH	H	H
24	H	OH	OH	H	H	OH	H	H

Table 2. Biological evaluation in vitro.

Product	IC50 value (μM)			FRAP value(mmol/g)
	AChE inhibitory activity	BuChE inhibitory activity	MAO-B inhibitory activity	Antioxidant activity
1	78.49 ± 2.84	44.82 ± 2.35	>700	0.51 ± 0.09
2	>100	13.06 ± 0.03	>700	0.16 ± 0.05
3	17.97 ± 1.13	16.15 ± 2.18	73.45 ± 11.97	15.43 ± 0.19
4	105.42 ± 2.92	34.71 ± 1.87	>700	7.73 ± 0.12
5	>100	14.39 ± 1.94	>700	0.42 ± 0.01
6	68.25 ± 0.72	21.17 ± 0.65	>700	0.66 ± 0.08
7	16.39 ± 0.19	2.76 ± 0.57	204.61 ± 6.92	2.29 ± 0.02
8	13.13 ± 1.35	18.86 ± 0.43	65.75 ± 4.61	10.51 ± 0.23
9	100.59 ± 2.02	30.14 ± 3.06	>700	0.67 ± 0.04
10	>100	10.57 ± 0.85	>700	1.47 ± 0.04
11	40.37 ± 2.09	75.60 ± 4.01	>700	0.41 ± 0.08
12	8.45 ± 0.16	24.81 ± 3.81	63.36 ± 4.04	11.75 ± 0.12
13	42.44 ± 3.16	70.70 ± 5.75	>700	0.61 ± 0.11
14	84.57 ± 1.67	46.35 ± 6.78	503.05 ± 12.56	2.98 ± 0.22
15	13.31 ± 2.26	26.53 ± 0.98	562.06 ± 7.13	10.40 ± 0.48
16	82.81 ± 1.43	21.82 ± 2.54	>700	0.35 ± 0.05
17	12.58 ± 1.28	13.15 ± 0.35	>700	13.16 ± 0.68
18	74.29 ± 3.72	29.27 ± 4.41	>700	0.38 ± 0.07
19	27.12 ± 0.66	25.76 ± 3.61	231.62 ± 17.19	12.75 ± 0.65
20	19.21 ± 0.68	>100	>700	0.42 ± 0.06
21	8.75 ± 0.63	20.25 ± 1.60	>700	14.64 ± 0.53
22	3.04  ±  0.32	8.37 ± 0.68	27.03 ± 0.50	41.42 ± 0.35
23	13.74 ± 0.32	9.92 ± 0.54	>700	12.84 ± 0.13
24	30.90 ± 1.27	70.92 ± 4.22	330.04 ± 6.49	8.41 ± 0.11
Donepezil	0.021  ±  0.001	4.10  ±  0.18
Rasagiline			0.125 ± 0.005
Ascorbic Acid				3.79 ± 0.08

Each value represents the mean  ±  SD (n = 3).

Figure 1. Effect of compounds 2, 20, 22 on the average total distance of zebrafish juveniles. (Compared with the control group, *p < .05 had a significant difference, **p < .01 had a very significant difference; compared with the model group, ^#p < .05 had a significant difference, ^##p < .01 had a very significant difference).

Figure 2. Statistical graph of the total trajectory of zebrafish juveniles exposed to different concentrations of compound 22 for 72 hpf.