Title:Discovery of Anti-Alzheimer Agents: Current Ligand-Based Approaches toward the Design of Acetylcholinesterase Inhibitors
VOLUME: 12 ISSUE: 6
Author(s):A. Speck-Planche, F. Luan and M. N.D.S. Cordeiro
Affiliation:REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
Keywords:AChE inhibitors, QSAR, 3D-QSAR, linear discriminant analysis, fragments, AChE, anti-AD agents, Ligand-Based Virtual Screening (LB-VS), parsimony, ArOCON, LBDD
Abstract:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive dementia and loss of
cognitive abilities. Until now, AD remains incurable. The principal biological target for AD therapy is
acetylcholinesterase (AChE). Thus, the search for new drug candidates like AChE inhibitors constitutes an essential part
for the discovery of more potent anti-AD agents. In general terms, rational drug design methodologies have played a
decisive role. The present work is focused on the current state of the Ligand-Based Drug Design (LBDD) methods which
have been applied to the elucidation of new molecular entities with high anti-AChE activity. Also, as a contribution to this
field, we suggest a promising fragment-based approach for the search and prediction of new AChE inhibitors and for the
fast and efficient extraction of substructural alerts which are responsible for the anti-AChE activity.
