Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

Mohsin, Noor ul Amin; Ahmad, Matloob

doi:10.1590/s2175-97902019000418325

Cited by 17 publications

(7 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…León et al developed a series of tacrine-dihydropyridine hybrids decorated with pyrin scaffolds. 226 The series was evaluated for inhibitory potential against acetylcholinesterase. Compound 86 had tenfold the activity (IC 50 = 0.0048±0.001) of the donepezil standard (0.049±0.005; Figure 44).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

Ling

Hao

Liang

et al. 2021

DDDT

220

114

View full text Add to dashboard Cite

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

show abstract

Section: Alzheimer's Diseasementioning

confidence: 99%

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

Ling

Hao

Liang

et al. 2021

DDDT

220

114

View full text Add to dashboard Cite

show abstract

“…Donepezil hydrochloride with the formula of C 24 H 30 ClNO 3 and molecular weight of 416 Dalton is a second-generation acetylcholine esterase inhibitor (AChEI) that was first produced by the Eisai Company (1)(2)(3). This drug consists of a benzylpiperidine part bound to dimethoxy indanone via the methylene group (4). Donepezil binds selectively, reversibly, and noncompetitively to the peripheral anionic site of acetylcholine esterase (AChE) (2,5).…”

Section: Contextmentioning

confidence: 99%

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

et al. 2022

View full text Add to dashboard Cite

: Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer's disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson's disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer's and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer's diseases, and more comprehensive studies are needed.

show abstract

“…Diverse structural characteristics of the both enzymes contribute to their substrate particularity: Small molecules such as ACh have a higher affinity toward AChE, whereas numerous peptides have more selectivity for BuChE (Taylor and Radic, 1994). Based on studies, the benzylic moiety of donepezil interacts with the CAS and dimethoxyindanone moiety interacts with the PAS of the AChE (Mohsin and Ahmad, 2020). Donepezil (donepezil hydrochloride, under the brand name Aricept) is a medication used for the symptomatic treatment of mild-to-moderate AD, which was introduced in 1996 (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…As anti-AD activity of donepezil has been proven from various mechanistic points of view, it has been considered as the main scaffold in the design and synthesis of a varied range of compounds against AD ( Sugimoto et al, 2002 ; Agatonovic-Kustrin et al, 2018 ; Piemonyese et al, 2018 ; Mohsin and Ahmad, 2020 ). Herein, we focused on the benzylpyridinium salts, which have shown very good ChE inhibitory activity mimicking the structure of donepezil.…”

Section: Introductionmentioning

confidence: 99%

Recent developments in the design and synthesis of benzylpyridinium salts: Mimicking donepezil hydrochloride in the treatment of Alzheimer’s disease

et al. 2022

View full text Add to dashboard Cite

Background: Alzheimer’s disease (AD) is an advanced and irreversible degenerative disease of the brain, recognized as the key reason for dementia among elderly people. The disease is related to the reduced level of acetylcholine (ACh) in the brain that interferes with memory, learning, emotional, and behavior responses. Deficits in cholinergic neurotransmission are responsible for the creation and progression of numerous neurochemical and neurological illnesses such as AD.Aim: Herein, focusing on the fact that benzylpyridinium salts mimic the structure of donepezil hydrochlorideas a FDA-approved drug in the treatment of AD, their synthetic approaches and inhibitory activity against cholinesterases (ChEs) were discussed. Also, molecular docking results and structure–activity relationship (SAR) as the most significant concept in drug design and development were considered to introduce potential lead compounds. Key scientific concepts: AChE plays a chief role in the end of nerve impulse transmission at the cholinergic synapses. In this respect, the inhibition of AChE has been recognized as a key factor in the treatment of AD, Parkinson’s disease, senile dementia, myasthenia gravis, and ataxia. A few drugs such as donepezil hydrochloride are prescribed for the improvement of cognitive dysfunction and memory loss caused by AD. Donepezil hydrochloride is a piperidine-containing compound, identified as a well-known member of the second generation of AChE inhibitors. It was established to treat AD when it was assumed that the disease is associated with a central cholinergic loss in the early 1980s. In this review, synthesis and anti-ChE activity of a library of benzylpyridinium salts were reported and discussed based on SAR studies looking for the most potent substituents and moieties, which are responsible for inducing the desired activity even more potent than donepezil. It was found that linking heterocyclic moieties to the benzylpyridinium salts leads to the potent ChE inhibitors. In this respect, this review focused on the recent reports on benzylpyridinium salts and addressed the structural features and SARs to get an in-depth understanding of the potential of this biologically improved scaffold in the drug discovery of AD.

show abstract

Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

Cited by 17 publications

References 62 publications

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Recent developments in the design and synthesis of benzylpyridinium salts: Mimicking donepezil hydrochloride in the treatment of Alzheimer’s disease

Contact Info

Product

Resources

About