Inhibition of acetylcholinesterase by two arylderivatives: 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-1,5-(3aH)-dione and cis-N-p-Acetoxy-phenylisomaleimide

Figures & data

Scheme 1 Synthesis of arylderivatives 1, 2, 3 and 4.

Table I.  Inhibitory effects of 3 and 4 on AChE activity.

Compounds	^aKi (μM)	k+2 (s^− 1)	ΔGbind (kcal/mol)	Ntot	∫occ	^bKi (μM)
3	4.72 ± 2.3	2.4 × 10^− 2 ± 0.69	− 9.22	2	49	0.157
4	3.6 ± 1.8	1.2X10^− 2 ± 0.31	− 8.58	2	30	0.513

^a Experimental data and

^b calculated data, N_tot is the number of clusters by AutoDock; ∫_occ is the number of results in the top clusters.

Figure 1 Time and concentration dependent inhibition on AChE activity for 4. Plot A shows the progressive development of inhibition produced by reaction of AChE with four different concentrations of 4, plotted as a semilogarithmic curve in accordance with Equation 1. The results are the mean ± S. E. of three experiments, each one being performed in duplicate. There was a significant difference (*P < 0.05) in relation to the control (without inhibitor). Plot B shows the relationship between the Kapp ^{− 1} versus [I]^{− 1}. The plot was made in accordance with Equation 2.

Figure 2 Dialysis kinetic method that shows time dependent AChE activity: full circles = without inhibitors; triangles = 3+ edrophonium; clear circles = 3. Each value represents the mean ± S. E. n = 6, *P < 0.05 in respect to the control (without inhibitors).

Figure 3 Graphical representations of the binding modes of compounds 3 and 4 in the catalytic site of AChE (PDB 1B41).