Modified Tacrine Derivatives as Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Synthesis, Biological Evaluation, and Molecular Modeling Study.

ABSTRACT: To develop multitarget-directed ligands (MTDLs) as potential treatments for Alzheimer's disease (AD) and to shed light on the effect of the chromene group in designing these ligands, 35 new tacrine-chromene derivatives were designed, synthesized, and biologically evaluated. Compounds 5c and 5d exhibited the most desirable multiple functions for AD; they were strong hAChE inhibitors with IC₅₀ values of 0.44 and 0.25 μM, respectively. Besides, their potent BuChE inhibitory activity was 10- and 5-fold more active than rivastigmine with IC₅₀ = 0.08 and 0.14 μM, respectively. Moreover, they could bind to the peripheral anionic site (PAS), influencing Aβ aggregation and decreasing Aβ-related neurodegeneration, especially compound 5d, which was 8

SUBMITTER: Fares S 

PROVIDER: S-EPMC10373466 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature