New Approach in Development of Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease

Abstract

Acetylcholinesterase inhibitors (AChEIs) portray the main group ofdrugs currently used for the treatment of Alzheimer’s disease (AD).In this article we present new approaches for the development ofAChEIs including the design and synthesis of dual binding siteinhibitors and multi-target-directed ligands (MTDLs). Dual binding siteinhibitors can be designed as donepezil derivatives or as homo- orheterodimeric CAS ligands. MTDLs reveal AChEI moleculeinteracting with other targets relevant for the pathophysiology of ADor other symptoms commonly found in the AD patients. MTDLs canbe designed by linking AChEI molecules with pharmacophoricgroups of other active drug and by creating a hybrid molecule.These strategies lead to the development of new AChEIs withincreased potency, therapeutic efficacy for the treatment ofsymptoms and attenuating the pathogenesis of AD.Keywords: acetylcholinesterase inhibitor, Alzheimer’s disease, dualbinding site inhibitor, multi target-directed ligand