Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors
- 30 March 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Medicinal Chemistry Letters
- Vol. 7 (5) , 470-475
Abstract
An ecofriendly synthetic pathway for the synthesis of donepezil precursors is described. Alternative energy sources were used for the total synthesis in order to improve yields, regioselectively, and rate of each synthetic step and to reduce the coproduction of waste at the same time. For all products, characterized by an improved structural rigidity respect to donepezil, the inhibitor activity on AChE, the selectivity vs BuChE, the side-activity on BACE-1, and the effect on SHSY-5Y neuroblastoma cells viability were tested. Two potential new lead compounds for a dual therapeutic strategy against Alzheimer’s disease were envisaged.Keywords
Funding Information
- European Social Fund Plus
- Regione Calabria
This publication has 28 references indexed in Scilit:
- From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffoldBioorganic & Medicinal Chemistry Letters, 2015
- Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernuaBioorganic & Medicinal Chemistry, 2015
- Computer-Aided Structure-Based Design of Multitarget Leads for Alzheimer’s DiseaseJournal of Chemical Information and Modeling, 2014
- Dual Inhibitors of β-Amyloid Aggregation and Acetylcholinesterase as Multi-Target Anti-Alzheimer Drug CandidatesCurrent Topics in Medicinal Chemistry, 2013
- Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrilsBioorganic & Medicinal Chemistry Letters, 2011
- Beyond the Cholinergic Hypothesis: Do Current Drugs Work in Alzheimer's Disease?CNS Neuroscience & Therapeutics, 2010
- Progress toward the development of a viable BACE‐1 inhibitorDrug Development Research, 2009
- Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and β-secretaseBioorganic & Medicinal Chemistry, 2009
- The significance of neuroinflammation in understanding Alzheimer’s diseaseJournal of Neural Transmission, 2006
- BACE1: The β-Secretase Enzyme in Alzheimer's DiseaseJournal of Molecular Neuroscience, 2004