Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta.

ABSTRACT: Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer's disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention--compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM). Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE) (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM), and it inhibits amyloid beta aggregation (35.8% at 10 μM). Kinetic studies show that the developed compounds act as mixed or non-

SUBMITTER: Hebda M 

PROVIDER: S-EPMC6273065 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature