Insights into the molecular basis of acetylcholinesterase inhibition by xanthones: an integrative <i>in silico</i> and <i>in vitro</i> approach

Alawi, Mohammed Saeed; Khalid, Asaad; Mohamed, Magdi A.; Khalid, Asaad; Ismail, Esraa; Alfatih, Fatima; Naz, Sehrish; Ul-Haq, Zaheer

doi:10.1080/08927022.2019.1691203

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…The derivatives also exhibited effects on BChE, but weaker than those against AChE. Derivatives of xanthones have also been studied in many other studies [532][533][534][535][536]. The results obtained in them were similar to each other.…”

Section: Xanthonessupporting

confidence: 53%

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka

Herbet

2021

IJMS

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Acetylcholinesterase (AChE) plays an important role in the pathogenesis of neurodegenerative diseases by influencing the inflammatory response, apoptosis, oxidative stress and aggregation of pathological proteins. There is a search for new compounds that can prevent the occurrence of neurodegenerative diseases and slow down their course. The aim of this review is to present the role of AChE in the pathomechanism of neurodegenerative diseases. In addition, this review aims to reveal the benefits of using AChE inhibitors to treat these diseases. The selected new AChE inhibitors were also assessed in terms of their potential use in the described disease entities. Designing and searching for new drugs targeting AChE may in the future allow the discovery of therapies that will be effective in the treatment of neurodegenerative diseases.

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Section: Xanthonessupporting

confidence: 53%

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka

Herbet

2021

IJMS

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“…Remarkably, all eighteen xanthone derivatives (2a-2r) have four different hydrocarbon substituents, including alkyl, alkenyl, alkynyl, and alkylated-phenyl groups possessed stronger AChE inhibitory effect than 1. In particular, 2g and 2j were found to exhibit an excellent inhibitory effect amongst the derivatives with the lowest IC 50…”

Section: Discussionmentioning

confidence: 96%

Synthesis of 1-Hydroxy-3-O-Substituted Xanthone Derivatives and their Structure-activity Relationship on Acetylcholinesterase Inhibitory Effect

Vanessa

Teh

Lam

et al. 2021

Preprint

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Xanthones are valuable compounds in drug design and development, attributed to their multi-dimensional pharmacological properties, including anti-cancer, anti-bacterial, anti-malarial, anti-inflammatory and anti-cholinesterase. This study focused on the synthesis of 1,3-dihydroxyxanthone (1) and its new 1-hydroxy-3-O-substituted derivatives with alkyl (2a-2f), alkenyl (2g-2k), alkynyl (2l-2n) and alkylated phenyl (2o-2r) groups and were synthesised in a high percentage yield of >70%, except for 2l and 2p. Their structures were confirmed by MS, NMR and FTIR spectroscopic techniques. The evaluation of acetylcholinesterase (AChE) inhibitory activities showed that all the substituted xanthones (2a-2r) are more potent than 1. Compounds 2g and 2j are the strongest AChE inhibitors with the IC50 values of 20.8 and 21.5 μM and their enzyme kinetic analyses indicated that these derivatives possess a mixed-mode inhibition, where they targeted both the active sites and allosteric sites of AChE. Molecular docking study revealed that 2g binds favourably to the active site of AChE via π–π stacking and hydrogen bonding, in addition to π-alkyl interaction and alkyl interaction from the substituent group. The xanthone derivatives are identified as potential lead compounds for further development of Alzheimer’s disease treatments.

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“…Xanthones, a class of oxygenated heterocyclic compounds with a dibenzo-γ-pyrone scaffold, were first isolated by Schmidt, in 1855, from the mangosteen fruit. Xanthones ( Figure 11 a) are commonly found in nature in higher plants, lichen, and fungi from terrestrial and marine sources [ 22 , 110 ]. Both natural and synthetic xanthones contain quite diverse biological activities, depending on the substitution on the scaffold and, because of that, the xanthonic scaffold is considered a “privileged structure”.…”

Section: Multitarget Therapymentioning

confidence: 99%

“…Both natural and synthetic xanthones contain quite diverse biological activities, depending on the substitution on the scaffold and, because of that, the xanthonic scaffold is considered a “privileged structure”. Some of these compounds have shown the ability to inhibit AChE and MAO enzymes, to act as antioxidants and to inhibit the aggregation of Aβ peptides [ 101 , 110 ]. The majority of xanthones with multiple activities are AChE/BChE and AChE/MAO inhibitors, but there are also reports of xanthones with AChE or MAO or Aβ disaggregation and antioxidant inhibitory activities [ 22 ].…”

Section: Multitarget Therapymentioning

confidence: 99%

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

et al. 2020

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Alzheimer’s disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for AD treatment. One of the most promising compounds, a marine-derived acidic oligosaccharide (GV-971) just passed phase III clinical trials with a unique mechanism of action. Combination therapy and multitargeted-directed ligand therapy (MTDL) are also two important strategies, with several examples in clinical trials, based on the belief that the best approach for AD is a therapy capable of modulating multiple target pathways. Drug repurposing, a strategy that requires a smaller investment and is less time consuming, is emerging as a strong contender with a variety of pharmacological agents resurfacing in an attempt to identify a therapeutic candidate capable of modifying the course of this disease.

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Insights into the molecular basis of acetylcholinesterase inhibition by xanthones: an integrative in silico and in vitro approach

Cited by 8 publications

References 37 publications

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Synthesis of 1-Hydroxy-3-O-Substituted Xanthone Derivatives and their Structure-activity Relationship on Acetylcholinesterase Inhibitory Effect

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

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