Correction to Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3ß for the Treatment of Alzheimer's Disease.

[This corrects the article DOI: 10.1021/acsomega.2c03368.].

Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3ß for the Treatment of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD) is very complex, and there are many hypotheses. Therefore, the development of a multi-target-directed-ligand may be an effective therapeutic strategy. Our previous study showed that notopterol (a natural product from Notopterygium) is a dual BACE1/GSK3ß inhibitor. In this study, we designed and synthesized 48 notopterol derivatives with furacoumarin as a scaffold in order to enhance their balanced AChE/BACE1/GSK3ß inhibitory activity. Fortunately, 1c showed effective inhibitory activity against AChE (58.7% at 1.0 µM), BACE1 (48.3% at 20 µM), and GSK3ß (40.3% at 10 µM). Furthermore, 1c showed good blood-brain barrier penetrability, suitable bioavailability, and oral safety. More importantly, 1c could ameliorate the impaired learning and memory in Aß-induced AD mice. In conclusion, we reported the triple inhibitor of AChE/BACE1/GSK3ß lead compounds based on a furocoumarin scaffold of notopterol for the first time, which provides a potential new strategy for the treatment of AD.