AUTHOR=Wang Wei , Pan Tingting , Su Rui , Chen Mingbin , Xiong Wandi , Xu Congjun , Huang Ling 

TITLE=Discovery of novel melatonin–mydroxyquinoline hybrids as multitarget strategies for Alzheimer’s disease therapy

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1374930

DOI=10.3389/fchem.2024.1374930

ISSN=2296-2646

ABSTRACT=<p>Alzheimer’s disease (AD) is a neurodegenerative disease that seriously affects human health, and current treatment strategies are far from meeting clinical needs. Inspired by multi-target drug design strategies, a series of novel natural products-based melatonin–hydroxyquinoline hybrids were designed and synthesized, targeting anti-oxidation and metal-chelating at the same time. Most of the compounds showed significant oxygen radical absorbance capacity and Aβ<sub>1–42</sub> aggregation inhibition. Moreover, the compounds possess good blood-brain barrier permeability. <bold>6b</bold> and <bold>6c</bold> have a good ability to alleviate oxidative stress induced by hydrogen peroxide. <bold>6b</bold> and <bold>6c</bold> possess metal-chelating properties with the chelation ratio being 2:1. Furthermore, <bold>6b</bold> can significantly mitigate metal-induced Aβ aggregation. This work may provide a new multi-target treatment strategy for Alzheimer’s disease.</p>