8-HYDROXYQUINOLINES: A PROMISING PHARMACOPHORE POTENTIALLY DEVELOPED AS DISEASE-MODIFYING AGENTS FOR NEURODEGENERATIVE DISEASES: A REVIEW

Abstract

8-Hydroxyquinoline (8HQ) is an attractive heterocyclic scaffold with well-known metal chelating property, broad-ranging pharmacological activities, and preferrable drug-likeness, thus, it had gained a continual attention in areas of drug development, especially, drug repurposing. Alzheimer’s disease (AD) is one of globally health concern in an era of aging society and its management is considered challenging as effective disease-modifying drugs are still clinically unavailable. Loss of metal ion homeostasis is one of key factors contributing to pathogenesis and progression of AD in which its imbalance could trigger many related key factors and harmful events, especially, oxidative neuronal damages. Hence, restoration of homeostasis and distribution of brain’s metal ions served to be a promising strategy for development of disease-modifying agents. In this review, essential key points relating to AD pathogenesis, roles of metal ions in AD, and pioneer 8HQ-based compounds are introduced. A series of recently reported 8HQ-based neuroprotective compounds (i.e., derivatives, hybrids, conjugates, and metal complexes) focusing on compounds acting as metal chelators are reviewed. Related 8HQ-based neuroprotective compounds with other mechanisms of actions are also discussed. Additionally, summary of key contents is included to provide an overview of current development situations. Taken together, this article would be beneficial and inspiring for the related future drug design and development to tackling an increasing prevalence of neurodegenerations in the global aging society. © 2022 The Japan Institute of Heterocyclic Chemistry.