Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is characterized by memory loss, cognitive impairment, and functional decline leading to dementia and death. AD imposes neuronal death by the intricate interplay of different neurochemical factors, which continue to inspire the medicinal chemist as molecular targets for the development of new agents for the treatment of AD with diverse mechanisms of action, but also depict a more complex AD scenario. Within the wide variety of reported molecules, this review summarizes and offers a global overview of recent advancements on naphthoquinone (NQ) and anthraquinone (AQ) derivatives whose more relevant chemical features and structure-activity relationship studies will be discussed with a view to providing the perspective for the design of viable drugs for the treatment of AD. In particular, cholinesterases (ChEs), β-amyloid (Aβ) and tau proteins have been identified as key targets of these classes of compounds, where the NQ or AQ scaffold may contribute to the biological effect against AD as main unit or significant substructure. The multitarget directed ligand (MTDL) strategy will be described, as a chance for these molecules to exhibit significant potential on the road to therapeutics for AD.
Highlights
Alzheimer’s disease is deemed by World Health Organization as one of the most common neurodegenerative diseases and more than 80% of total dementia cases in elderly people
Alzheimer’s disease (AD) progression is characterized by the concurrence of different pathological occurring in parallel, such as Aβ aggregation, tau hyperphosphorylation andevents oligomeriAD in progression is as characterized by tau the hyperphosphorylation concurrence of different pathological event occurring parallel, such and oligomerizazation, synaptic dysfunctions, and inflammation
The cause of Alzheimer’s disease is still unknown, and the discovery of factors related to the key pathophysiological hallmarks of AD has not been able to uncover the source of the neurodegenerative processes observed in patients
Summary
Alzheimer’s disease is deemed by World Health Organization as one of the most common neurodegenerative diseases and more than 80% of total dementia cases in elderly people. Pharmaceuticals 2021, 14, 33 mitogen-activated protein kinase (MAPK) and sirtuin 1 (SIRT1), as an example (clinicaltrials.gov). The synergistic bedonepezil and memantine in combination regimen is showing ameliorated outcomes for tween donepezil and memantine in combination regimen is showing ameliorated outcognition, global assessment, daily activities, and neuropsychiatric symptoms, but lower comes for cognition, global assessment, daily activities, and neuropsychiatric symptoms, acceptability than monotherapy [10] In this have been paid with a view to disclosIn this scenario, scenario,the themedicinal medicinalchemistry chemistryefforts efforts have been paid with a view to dising novel chemotypes which could include in their structures the required pharmacophoric closing novel chemotypes which could include in their structures the required pharmacofeaturesfeatures to targettoone or more ofmore theseof factors in AD.
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