Design and synthesis of donepezil analogues as dual AChE and BACE-1 inhibitors

Gabr, Moustafa T.; Abdel-Raziq, Mohammed S.

doi:10.1016/j.bioorg.2018.06.031

Cited by 38 publications

(21 citation statements)

References 45 publications

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“…Drugs that target at least two molecular targets of AD were tested for efficacy against AD. A series of hybrid compounds produced by combining two drugs that inhibit AChE and BACE1 has been reported [234,235,236,237,238,239]. Other combinations were found to be effective in metal chelating activity and antioxidant properties with less toxicity [237,239].…”

Section: Drug Combinations As a Strategy For Ad Therapymentioning

confidence: 99%

“…A series of hybrid compounds produced by combining two drugs that inhibit AChE and BACE1 has been reported [234,235,236,237,238,239]. Other combinations were found to be effective in metal chelating activity and antioxidant properties with less toxicity [237,239]. Similarly, combinations of AChE with GSK3β inhibitors, MAO inhibitors, metal chelators, NMDAR inhibitors, 5-HT receptor inhibitors, histaminic receptors inhibitors and phosphodiesterase inhibitors have been studied [240].…”

Section: Drug Combinations As a Strategy For Ad Therapymentioning

confidence: 99%

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Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

Dhakal

Kushairi

Phan

et al. 2019

IJMS

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Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Lewy body dementia, etc. Alzheimer’s Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer’s Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer’s Disease.

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Section: Drug Combinations As a Strategy For Ad Therapymentioning

confidence: 99%

Section: Drug Combinations As a Strategy For Ad Therapymentioning

confidence: 99%

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

Dhakal

Kushairi

Phan

et al. 2019

IJMS

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“…Another interesting series of analogues typified by structure 16 [33] possessed a favorable combination of groups, resulting in a dual AChE/BACE-1 inhibitor potentially endowed with chelating ability, thanks to the amidic portions. As a matter of fact, compound 16 was a low nanomolar inhibitor of the two target enzymes (IC 50 , AChE = 4:11 nM, BACE − 1 = 18:3 nM).…”

Section: Dual Che/bace-1 Inhibitorsmentioning

confidence: 99%

Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations

Maramai

Benchekroun

Gabr

et al. 2020

BioMed Research International

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Neurodegenerative diseases represent nowadays one of the major health problems. Despite the efforts made to unveil the mechanism leading to neurodegeneration, it is still not entirely clear what triggers this phenomenon and what allows its progression. Nevertheless, it is accepted that neurodegeneration is a consequence of several detrimental processes, such as protein aggregation, oxidative stress, and neuroinflammation, finally resulting in the loss of neuronal functions. Starting from these evidences, there has been a wide search for novel agents able to address more than a single event at the same time, the so-called multitarget-directed ligands (MTDLs). These compounds originated from the combination of different pharmacophoric elements which endowed them with the ability to interfere with different enzymatic and/or receptor systems, or to exert neuroprotective effects by modulating proteins and metal homeostasis. MTDLs have been the focus of the latest strategies to discover a new treatment for Alzheimer’s disease (AD), which is considered the most common form of dementia characterized by neurodegeneration and cognitive dysfunctions. This review is aimed at collecting the latest and most interesting target combinations for the treatment of AD, with a detailed discussion on new agents with favorable in vitro properties and on optimized structures that have already been assessed in vivo in animal models of dementia.

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“…Belluti and co-workers [36] reported that compound 38 (Figure 3) with a benzophenone core, showed dual-target inhibitory potency against human AChE and BACE-1 (IC50 = 1.57 μM for AChE, 10.72% inhibition at 3.38 μM for BACE-1). Recently, a new compound 39 (Figure 3) with a benzophenone core was reported by the Gabr group [37],…”

Section: Ache and Bace-1 Multi-target Strategymentioning

confidence: 99%

Multi-target design strategies for the improved treatment of Alzheimer's disease

Zhang

Zhu

et al. 2019

European Journal of Medicinal Chemistry

156

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Alzheimer's disease (AD) is a multifactorial syndrome resulting in profound misery and poses a substantial burden on human health, economy, and society throughout the world. Based on the numerous AD-related targets in the disease network, multi-target design strategy is a crucial direction to seek for enhanced therapy, and multi-target drugs have the ability to regulate more targets than single-target drugs, affecting the disease network with more potency. Herein, we highlight nine major targets associated with AD, which are acetylcholine esterase (AChE), beta-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE-1), glycogen synthase kinase 3 beta (GSK-3β), monoamine oxidases (MAOs), metal ions in the brain, N-methyl-D-aspartate (NMDA) receptor, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H3 receptor), and phosphodiesterases (PDEs), and their respective relationship to the disease network. Furthermore, eleven multi-target design strategies classified by the involvement of AChE and related promising compounds for improved therapy of AD in recent years are described based on the nine major targets.

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Design and synthesis of donepezil analogues as dual AChE and BACE-1 inhibitors

Cited by 38 publications

References 45 publications

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations

Multi-target design strategies for the improved treatment of Alzheimer's disease

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