Journey on Naphthoquinone and Anthraquinone Derivatives: New Insights in Alzheimer’s Disease

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.

Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

“…In conclusion, we can say that the disease begins with the stress induced by the interaction between AGE and RAGE, and Aβ, HMGB1, and S100 make it progress. The reduction in the levels of AGEs and RAGE, the increase in sRAGE, and the use of antioxidants could really have benefits in the prevention and in slowing down the progression of AD [ 142 , 143 ]. Aβ extracellular fibrillar aggregates have characteristics of AGEs and bind to RAGE in neurons and brain endothelial cells.…”

Long-Term Treatment of Cuban Policosanol Attenuates Abnormal Oxidative Stress and Inflammatory Response via Amyloid Plaques Reduction in 5xFAD Mice

“…Recent investigations indicate that the number of dementia patients is projected to increase by more than 131 million worldwide by 2050, together with the cost of dementia [ 1 ]. AD has a neuropathological hallmark consisting of extracellular amyloid plaque deposition composed of amyloid beta (Aβ) peptide and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau [ 2 , 3 , 4 ]. Amyloid plaques and NFT are mainly deposited in the brain, such as the hippocampus, entorhinal cortex, and basal forebrain, which influence learning, memory, and emotional behavior [ 5 ].…”

Mild Cognitive Impairment and Mild Dementia: The Role of Ginkgo biloba (EGb 761®)

“…Neurodegenerative diseases involve different groups of pathologies of the central nervous system, characterized by a progressive loss of synaptic transmission in some specific neuronal circuits. This information flow deficit, without any clear structural damage, is then followed by progressive neuronal death with loss of volume and obvious accumulation of toxic substances in both extra-(e.g., amyloid beta plaques) and intra-neuronal spaces (e.g., neurofibrillary tangles) [17][18][19]. Moreover, these disorders are classified considering clinical features (Parkinson or dementia), anatomic distribution of neurodegeneration (frontotemporal degenerations, spinocerebellar degenerations), or as a result of molecular abnormalities [20].…”