Synthesis and Evaluation of Novel Ligustrazine Derivatives as Multi-Targeted Inhibitors for the Treatment of Alzheimer's Disease.

ABSTRACT: A series of novel ligustrazine derivatives 8a⁻r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC₅₀ values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC₅₀ BuChE/IC₅₀ AChE = 2.91 × 10⁶; for 8r, IC₅₀ BuChE/IC₅₀ AChE = 1.32 × 10⁷). Of note, 8q and 8r also presented potent inhibitory activities against Aβ aggregation, with IC₅₀ values of 17.36 µM and 4

SUBMITTER: Wu W 

PROVIDER: S-EPMC6222487 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature