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

Two arylderivatives, 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-l,5-(3aH)-dione 3 and cis-N-p-Acetoxy-phenylisoma-leimide 4, were synthesized from anthranilic acid and para-aminophenol, respectively. The inhibitory effects of these compounds on acetylcholinesterase (AChE) activity were evaluated in vitro as well as by docking simulations. Both compounds showed inhibition of AChE activity (K-i = 4.72 +/- 2.3 mu M for 3 and 3.6 +/- 1.8 mu M for 4) in in vitro studies. Moreover, they behaved as irreversible inhibitors and made pi-pi interaction with W84 and hydrogen bonded with S200 and Y337 according to experimental data and docking calculations. The docking calculations showed Delta G bind (kcal/mol) of - 9.22 for 3 and - 8.58 for 4. These two compounds that can be use as leads for a new family of anti-Alzheimer disease drugs.