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-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 microM for 3 and 3.6 +/- 1.8 microM 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 deltaG 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.
Correa-Basurto
José
J
Sección de Graduados y Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, México, D. F 11340, México.
Espinosa-Raya
Judith
J
González-May
Mario
M
Espinoza-Fonseca
L Michel
LM
Vázquez-Alcántara
Iván
I
Trujillo-Ferrara
José
J
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013816:Thermodynamics
C512573:3a-acetoxy-5H-pyrrolo(1,2-a)(3,1)benzoxazin-1,5-(3aH)-dione; D048588:Benzoxazines; D002800:Cholinesterase Inhibitors; D008301:Maleimides; C512574:N-p-acetoxyphenylisomaleimide; D011758:Pyrroles; D000110:Acetylcholinesterase