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 |
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| Authors: | José Correa-Basurto Judith Espinosa-Raya Mario González-May L. Michel Espinoza-Fonseca Iván Vázquez-Alcántara José Trujillo-Ferrara |
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| Affiliation: | 1. Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Graduados y Departamento de Bioquímica, Plan de San Luis y Díaz Mirón, México, D.F., 11340, México;2. University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, MinneapolisMN 55455, USA |
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| 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 (Ki = 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. |
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| Keywords: | AChE Inhibitors Docking Alzheimer Anilines Arylderivatives Acetylcholinesterase |
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