Multifunctional Inhibitors of Cholinesterases for the Therapy of Alzheimer’s Disease (A Review)

An analysis of the results of the author’s research on the development of multifunctional compounds based on the cholinesterase inhibitors tacrine and amiridine as potential drugs for Alzheimer’s disease is presented. The screening system developed by the authors was used to study three series of tacrine conjugates and three series of amiridine conjugates. Effective cholinesterase inhibitors were found, that are capable of blocking AChE-induced and self-aggregation of beta-amyloid, of chelating metals and have a high antioxidant activity and favorable ADMET profile. It was shown that the spectrum of biological activity of the conjugates depends on both the structure of the second pharmacophore and the structure of the spacer.