Donepezil: An Important Prototype to the Design of New Drug Candidates for Alzheimer’s Disease

Simões, Maria Cecília R.; Viegas, Flávia Pereira Dias; Moreira, Marcella S.; Silva, Matheus de Freitas; Riquiel, Mariana M.; Rosa, Patricia Mattos da; Castelli, Maísa Rosa; Santos, Marcelo H. dos; Soares, Marisi G.; Viegas, Cláudio

doi:10.2174/1389557513666131119201353

Cited by 61 publications

(29 citation statements)

References 31 publications

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“…Acetyl-cholinesterase inhibitors (AChEIs), which delay the cognitive decline of AD (100), have a protective effect on the development of glaucoma. Topical rivastigmine lowered intraocular pressure (IOP) in rabbits (101).…”

Section: Visual System In Aging and Admentioning

confidence: 99%

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Albers

Gilmore

Kaye

et al. 2014

Alzheimer's & Dementia

485

379

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Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer’s disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and Alzheimer’s Disease”. The scientific sessions of the workshop focused on age-related and neuropathological changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the CNS are affected by Alzheimer pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.

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Section: Visual System In Aging and Admentioning

confidence: 99%

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Albers

Gilmore

Kaye

et al. 2014

Alzheimer's & Dementia

485

379

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“…The FDA approved anti-Alzheimer's drug, donepezil (Aricept) is cis1-benzil-4-[5,6-dimethoxy-(1-indanone)-2-yl]-methylpiperidine hydrochloride (Figure 14, Table 4), which is reversible, non-competitive and very effective AChE inhibitor (IC 50 = 5.7 nM) with less toxicity [107,108]. This drug is clinically used for the treatment of AD in patients with mild, moderate and severe stages of cognitive impairment at maximum 23mg/day dose [107].…”

Section: Donepezil Analogsmentioning

confidence: 99%

“…The majority of novel donezepil analogs were achieved by structural modifications in these two sub-structures and the spacer. These novel donepezil analogs are discussed below [108].…”

Section: Donepezil Analogsmentioning

confidence: 99%

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Saxena¹

2019

AND

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Alzheimer's Disease (AD) is characterized by the loss of memory and learning ability in elderly patients affecting large population worldwide. The enzyme Acetylcholinesterase (AChE), (E.C.3.1.1.7) plays a major role in the hydrolysis of the released neurotransmitter acetylcholine. Most of the clinically used drugs to treat AD are Acetylcholinesterase Inhibitors (AChEIs). These drugs can provide symptomatic benefits only and suffer with loss of therapeutic potential with time. Therefore, there is an urgent need of novel cholinesterase inhibitors with wider therapeutic window for the treatment of AD. The strategies targeting the AChE enzyme along with other target(s) like Butyrylcholinesterase (BChE), amyloid-β (Aβ), β-secretase-1 (BACE), metals (Cu 2+ , Zn 2+ , or Fe 2+), antioxidant properties and free radical scavenging capacity have been mainly focused in the last five years. A number of hybrid molecules incorporating sub-structures with the desired well-established pharmacological profile into a single scaffold have been investigated. The main sub structures used in developing these molecules are derived from diverse chemical classes such as acridine, quinoline, carbamates, huperzine and other heterocyclic analogs. It has been followed by optimization of activity through structural modifications of the prototype molecules for developing the Structure Activity Relationship (SAR). This has led to the development of novel molecules with desired AChE inhibitory activity along with other desirable pharmacological properties. This review summarizes the current therapeutic strategies for the development of these AChEI in the last seven years.

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“…Two examples of such inhibitors are physostigmine, used to treat glaucoma, and galantamine, a drug investigated for the treatment of moderate Alzheimer's disease 24 . In the case of minaprine, an antidepressant, it was just recently shown that this drug is also a cognitive enhancer that may halt the progression of Alzheimer's disease 25 . It is thus attractive that CRANK identified minaprine as a member of a community of primarily cholinesterase inhibitors, which suggests minaprine's potential for drug repurposing for Alzheimer's disease.…”

Section: Network Of Medical Drugs With Shared Target Proteinsmentioning

confidence: 99%

Prioritizing network communities

Žitnik

Sosič

Leskovec

2018

Preprint

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Uncovering modular structure in networks is fundamental for advancing the understanding of complex systems in biology, physics, engineering, and technology. Community detection provides a way to computationally identify candidate modules as hypotheses, which then need to be experimentally validated. However, validation of detected communities requires expensive and time consuming experimental methods, such as mutagenesis in a wet biological laboratory. As a consequence only a limited number of communities can be experimentally validated, and it is thus important to determine which communities to select for downstream validation and experimentation. Here we develop CRANK, an automatic method for prioritizing network communities and identifying the most promising ones for further experimentation. CRANK efficiently evaluates robustness and magnitude of structural features of each community and then combines these features to obtain the community prioritization. CRANK can be used with any community detection method and scales to large networks. It needs only information provided by the network structure and does not require any additional metadata or labels. However, when available, CRANK can incorporate domain-specific information to further boost performance. Experiments on many diverseand important biological networks demonstrate that the proposed approach effectively prioritizes communities, yielding a near 50-fold improvement in community prioritization over a baseline ordering of detected communities. Taken together, CRANK represents a networkbased approach to identify high-quality communities, even for domains at the frontier of science where supervised meta information is not available.

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Donepezil: An Important Prototype to the Design of New Drug Candidates for Alzheimer’s Disease

Cited by 61 publications

References 31 publications

At the interface of sensory and motor dysfunctions and Alzheimer's disease

At the interface of sensory and motor dysfunctions and Alzheimer's disease

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Prioritizing network communities

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