Design, synthesis, and neuroprotective activity of salidroside-based dual inhibitors of selective monoamine oxidase B and amyloid-β aggregation

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Research Pub Date : 2025-01-02 DOI:10.1007/s00044-024-03367-0

Juan Zhang, Kong-Kai Zhu, Kai-Ming Wang, Cheng-Shi Jiang

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Abstract

This study focuses on the design, synthesis, and evaluation of a series of salidroside derivatives (pOBZ-1~pOBZ-11) for their potential as inhibitors of monoamine oxidase B (MAO-B) and amyloid beta (Aβ₄₂) aggregation, and neuroprotective agents. Among the synthesized derivatives, pOBZ-1 and pOBZ-2 exhibited superior MAO-B inhibitory activity compared to salidroside, with notable selectivity over MAO-A. These compounds demonstrated linear competitive inhibition. Additionally, the derivatives effectively inhibited Aβ₄₂ aggregation and protected SH-SY5Y cells from Aβ₄₂ and hydrogen peroxide (H₂O₂)-induced neurotoxicity. The findings suggest that pOBZ-2, in particular, holds promise as a therapeutic candidate for Alzheimer’s disease.

Graphical abstract

Novel dual inhibitors of selective MAO-B/amyloid-β aggregation

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来源期刊

Medicinal Chemistry Research 医学-医药化学

CiteScore

4.70

自引率

3.80%

发文量

162

审稿时长

5.0 months

期刊介绍： Medicinal Chemistry Research (MCRE) publishes papers on a wide range of topics, favoring research with significant, new, and up-to-date information. Although the journal has a demanding peer review process, MCRE still boasts rapid publication, due in part, to the length of the submissions. The journal publishes significant research on various topics, many of which emphasize the structure-activity relationships of molecular biology.