Preparation, anticholinesterase activity, and docking study of new 2-butenediamide and oxalamide derivatives

Figures & data

Scheme 1. Synthesis of the target compounds 1a–h and 2a–h.

Table 1. Anticholinesterase activity of IC₅₀ (μM) and selectivity of compounds 1a–h and 2a–h on AChE and BuChE.

			IC50 (µM)
Compounds	R^1	R^2	AChE^a	BuChE^b	Selectivity index^c
1a	H	Cl	>100	1.86 ± 0.029	0.02
1b	CH3	Cl	>100	72.02 ± 0.058	0.72
1c	C2H5	Cl	>100	>100	–
1d	OCH3	Cl	>100	>100	–
1e	OC2H5	Cl	>100	>100	–
1f	F	Cl	>100	>100	–
1g	Cl	Cl	>100	>100	–
1h	Br	Cl	>100	>100	–
2a	H	Cl	1.51 ± 0.121	>100	62.11
2b	CH3	Cl	87.09 ± 0.011	11.22 ± 0.021	0.12
2c	C2H5	Cl	26.30 ± 0.045	35.48 ± 0.24	1.35
2d	OCH3	Cl	>100	>100	–
2e	OC2H5	Cl	>100	>100	–
2f	F	Cl	2.47 ± 0.18	>100	40.48
2g	Cl	Cl	8.31 ± 0.154	7.07 ± 0.065	0.85
2h	Br	Cl	5.49 ± 0.32	>100	18.21
Neostigmin			6.76 ± 0.012	14.45 ± 0.015	2.13
Ambenonium			4.07 ± 0.068	6.02 ± 0.045	1.48

^a50% inhibitory concentration (means ± SD of three experiments) of AChE.

^b50% inhibitory concentration (means ± SD of three experiments) of BuChE.

^cSelectivity for AChE = IC50 (BuChE)/IC50 (AChE).

Figure 1. Docking model of compound 2a and TcAChE complex.

Figure 2. Docking model of compound 1a and HuBuChE complex.

Figure 3. (a) UV spectrum of compound 1a (100 μM). (b) Spectrum of a mixture of 1a (100 μM) and ZnSO₄ (100 μM). (c) Spectrum of a mixture of 1a (100 μM) and CuSO₄. (d) Spectrum of a mixture of 1a (100 μM) and FeSO₄ (100 μM).

Figure 4. (a) UV spectrum of compound 2a (100 μM). (b) Spectrum of a mixture of 2a (100 μM) and ZnSO₄ (100 μM). (c) Spectrum of a mixture of 2a (100 μM) and CuSO₄. (d) Spectrum of a mixture of 2a (100 μM) and FeSO₄ (100 μM).