Design, synthesis and anti-Alzheimer's disease activity evaluation of cinnamyl triazole compounds
10.16438/j.0513-4870.2024-0724
- VernacularTitle:肉桂酰三氮唑化合物的设计、合成及抗阿尔茨海默症活性评价
- Author:
Wen-ju LEI
;
Zhong-di CAI
;
Lin-jie TAN
;
Mi-min LIU
;
Li ZENG
;
Ting SUN
;
Hong YI
;
Rui LIU
;
Zhuo-rong LI
- Publication Type:Research Article
- Keywords:
cinnamamide/ester triazole;
esign and synthesis;
acetylcholine- sterase;
italic>β amyloid protein;
Alzheimer's disease
- From:
Acta Pharmaceutica Sinica
2025;60(1):150-163
- CountryChina
- Language:Chinese
-
Abstract:
19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC50 = 2.03 ± 2.45 μmol·L-1) in APPswe cells and acetylcholinesterase inhibiton (IC50 = 4.88 ± 4.70 μmol·L-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.
