8-Hydroxyquinoline Derivatives as Drug Candidates for the Treatment of Alzheimer's Disease

Alzheimer's disease (AD) is the most prevalent form of dementia among older adults worldwide. Amidst several hypotheses to explain the pathobiology of the disease are biochemical indicators such as β-amyloid (Aβ) plaques; neurofibrillary tangles, caused by hyperphosphorylated tau protein; oxidative stress; metal dyshomeostasis; low levels of acetylcholine, and neuroinflammation. Considering the multifactorial nature of AD, there has been an increase in research for novel multitarget compounds, mainly utilizing molecular hybridization for drug design. In this review, we focus on the 8-hydroxyquinoline moiety, a privileged metal-binding agent with Aβ antiaggregating properties, and its derivatives, aiming to have an effect on multiple molecular targets. Furthermore, the most prominent structure-activity relationships found on the analyzed compounds, along with the most promising strategies explored by researchers, are discussed. That way, we hope to provide a comprehensive perspective on the development of anti- Alzheimer agents based on the 8-hydroxyquinoline moiety in the last decade.