Molecular modelling, synthesis and acetylcholinesterase inhibition of ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate.
In silico analysis of ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate (2) predicts that this molecule should be successfully docked in the PAS, and easily accommodated in the CAS of AChE. The synthesis and the AChE/BuChE inhibition studies are reported, confirming that compound 2 is a potent and selective AChE inhibitor, and consequently, a new lead compound for further development into new dual CAS/PAS cholinergic agents for the treatment of Alzheimer's disease.
Soriano
Elena
E
Laboratorio de Radicales Libres y Química Computacional (LRL-QC, IQOG, CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain.
Samadi
Abdelouahid
A
Chioua
Mourad
M
de los Ríos
Cristóbal
C
Marco-Contelles
José
J
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D009287:Naphthyridines; C551006:ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo(b)(1,8)naphthyridine-3-carboxylate; D000110:Acetylcholinesterase