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

Abstract

Two arylderivatives, 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-1,5-(3aH)-dione 3 and cis-N-p-Acetoxy-phenylisomaleimide 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 μM for 3 and 3.6 ± 1.8 μM for 4) in in vitro studies. Moreover, they behaved as irreversible inhibitors and made π–π interaction with W84 and hydrogen bonded with S200 and Y337 according to experimental data and docking calculations. The docking calculations showed ΔG 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.

Keywords::

• AChE
• Inhibitors
• Docking
• Alzheimer
• Anilines
• Arylderivatives
• Acetylcholinesterase

Acknowledgements

We are grateful to CONACyT and COFAA and SIP-IPN for scholarships and financial support to the Authors. L.M.E.F's research is supported by grants from the Department of Biochemistry, Structural Biology and Biophysics, and the Minnesota Supercomputing Institute, University of Minnesota, USA.