Synthesis and biological evaluation of some dibenzofuran-piperazine derivatives

Figures & data

Figure 1. The chemical structures of beraprost and aglafolin.

Scheme 1. Synthesis of the compounds (2a-m).

Table 1. Inhibitory data (100 µM) for compounds 2a-m against arachidonic acid (AA, 350 µM) and collogen (5 µg/ml) induced platelet aggregation.

	% Inhibition
Compounds	AA (350 µM)	Collagen (5 µg/ml)
2a	4.7 ± 6.7	3.08 ± 4.34
2b	10.2 ± 7.1	7.93 ± 0.96
2c	5.8 ± 8.2	4.41 ± 4.63
2d	1.1 ± 1.6	NI
2e	2.8 ± 3.9	8.59 ± 5.40
2f	1.6 ± 1.2	3.60 ± 3.20
2g	11.0 ± 3.4	4.49 ± 4.27
2h	7.38 ± 8.9	1.79 ± 1.71
2i	7.6 ± 10.8	1.19 ± 2.06
2j	3.6 ± 3.6	1.66 ± 1.50
2k	9.5 ± 3.6	3.56 ± 3.22
2l	0.3 ± 0.3	2.20 ± 3.25
2m	100	1.87 ± 2.70
Aspirin	100	–

NI: no inhibition.

Table 2. IC₅₀ (µM) of the compound 2m on 350 µM AA-induced platelet aggregation.

Compound	IC50 (µM)
2m	26.1
Aspirin	3.9

Table 3. % AChE inhibition of the compounds and IC₅₀ values.

	AChE inhibition (%)
Compounds	1 mM	0.1 mM	IC50 (mM)*
2a	42.0 ± 3.44	41.12 ± 1.34	>1
2b	27.37 ± 2.11	19.17 ± 4.45	>1
2c	20.23 ± 4.24	10.81 ± 2.49	>1
2d	31.27 ± 2.45	11.26 ± 3.14	>1
2e	46.64 ± 3.46	3.63 ± 1.17	>1
2f	15.89 ± 2.35	4.39 ± 2.40	>1
2g	12.89 ± 2.54	1.92 ± 3.48	>1
2h	ND	ND	ND
2i	41.35 ± 1.75	30.22 ± 2.19	>1
2j	5.79 ± 2.54	1.78 ± 3.45	>1
2k	41.24 ± 3.41	3.92 ± 4.12	>1
2l	12.80 ± 2.21	0.23 ± 2.43	>1
2 m	ND	ND	ND
Donepezil	99.01 ± 4.89	95.52 ± 5.01	0.054 ± 0.002 (µM)

ND: not determined.

*IC₅₀: 50% inhibitory concentration (means ± SD of three independent experiments) of AChE.