Novel harmine derivatives as potent acetylcholinesterase and amyloid beta aggregation dual inhibitors for management of Alzheimer's disease.

ABSTRACT: In this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Aβ_1 - 42 aggregation. Notably, compounds 13 and 17d displayed potent drug - likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC₅₀ = 58.76 nM and 89.38 nM, respectively) as well as Aβ aggregation (IC₅₀ = 9.31 μM and 13.82 μM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Aβ_1 - 42</

SUBMITTER: Du H 

PROVIDER: S-EPMC10653770 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature