Chromones: privileged scaffolds for the production of multi-target-directed-ligand agents for the treatment of Alzheimer's disease

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder responsible for the great majority of age-related dementias affecting daily life through memory loss and cognitive impairment. From a molecular point of view, the most common neuropathological characteristics found in AD patients are abnormal protein deposits, particularly senile plaques (SP) and neurofibrillary tangles (NFT). Furthermore, the currently available pharmacological treatment only provides short-term improvements and is focused on the use of cholinesterase (ChEs) inhibitors or memantine, an approved medicine that is a glutamatergic N-methyl-D-aspartate (NMDA) receptor blocker. Areas covered: This review is focused on the relevance of chromones for future AD treatment. Structure-activity relationship (SAR) studies which look at the inhibition of amyloid-beta (A beta) plaque formation and aggregation and the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase are also discussed. Expert opinion: SAR studies are a useful strategy for the elucidation of structural features that improve compound-specific AD-related activities. The development of multi-target-directed ligands (MTDLs) represents an exciting challenge for organic chemists. As such, recently developed chromone-type compounds have a potential use as MTDLs for the treatment of AD.