4.8 Article

Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease

Journal

CHEMICAL SCIENCE
Volume 14, Issue 35, Pages 9293-9305

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d3sc00752a

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This study reports the design of flavonoids that can effectively target multiple pathological elements involved in Alzheimer's disease (AD). The findings reveal key structural features necessary for flavonoids to simultaneously regulate pathogenic targets. Mechanistic studies confirm that the versatile reactivities of the flavonoid are driven by its redox potential and direct interactions with pathogenic factors. This work highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD.
The underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological components, including oxidative stress, acetylcholinesterase, amyloid-& beta;, and metal ions, all playing a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple pathological elements involved in AD. Our systematic investigations revealed key structural features for flavonoids to simultaneously target and regulate pathogenic targets. Our findings led to the development of a highly promising flavonoid that exhibits a range of functions, based on a complete structure-activity relationship analysis. Furthermore, our mechanistic studies confirmed that this flavonoid's versatile reactivities are driven by its redox potential and direct interactions with pathogenic factors. This work highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD.

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