Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease

Zhang, Honghua; Wang, Yuying; Wang, Yuqing; Li, Xuelin; Wang, Shuzhi; Wang, Zhen

doi:10.1016/j.ejmech.2022.114606

Cited by 42 publications

(37 citation statements)

References 275 publications

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“…Several key enzymes that are frequently screened in the enzyme inhibition assays include cholinesterase for Alzheimer’s, amylase for diabetes, and lipase for obesity. In this respect, several inhibitors have been chemically designed, but many of them exhibit various side effects [ 51 , 52 ]. Thus, safe and effective inhibitors derived from natural sources represent a promising research direction.…”

Section: Resultsmentioning

confidence: 99%

Exploring the Artemisia Genus: An Insight into the Phytochemical and Multi-Biological Potential of A. campestris subsp. lednicensis (Spreng.) Greuter & Raab-Straube

Trifan

Czerwińska

Mardari³

et al. 2022

Plants

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The Artemisia L. genus includes over five hundred species with great economic and medicinal properties. Our study aimed to provide a comprehensive metabolite and bioactivity profile of Artemisia campestris subsp. lednicensis (Spreng.) Greuter & Raab-Straube collected from north-eastern Romania. Liquid chromatography with tandem high-resolution mass spectrometry (LC-HRMS/MS) analysis of different polarity extracts obtained from the aerial parts led to the identification of twelve flavonoids, three phenolic acids, two sesquiterpene lactones, two fatty acids, one coumarin, and one lignan. The antioxidant and enzyme inhibitory properties were shown in the DPPH (0.71–213.68 mg TE/g) and ABTS (20.57–356.35 mg TE/g) radical scavenging, CUPRAC (38.56–311.21 mg TE/g), FRAP (121.68–202.34 mg TE/g), chelating (12.88–22.25 mg EDTAE/g), phosphomolybdenum (0.92–2.11 mmol TE/g), anti-acetylcholinesterase (0.15–3.64 mg GALAE/g), anti-butyrylcholinesterase (0–3.18 mg GALAE/g), anti-amylase (0.05–0.38 mmol ACAE/g), anti-glucosidase (0.43–2.21 mmol ACAE/g), and anti-tyrosinase (18.62–48.60 mg KAE/g) assays. At 100 μg/mL, Artemisia extracts downregulated the secretion of tumor necrosis factor (TNF)-α in a lipopolysaccharide (LPS)-stimulated human neutrophil model (29.05–53.08% of LPS+ control). Finally, the Artemisia samples showed moderate to weak activity (minimum inhibitory concentration (MIC) > 625 mg/L) against the seventeen tested microbial strains (bacteria, yeasts, and dermatophytes). Overall, our study shows that A. campestris subsp. lednicensis is a promising source of bioactives with putative use as food, pharmaceutical and cosmetic ingredients.

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Section: Resultsmentioning

confidence: 99%

Exploring the Artemisia Genus: An Insight into the Phytochemical and Multi-Biological Potential of A. campestris subsp. lednicensis (Spreng.) Greuter & Raab-Straube

Trifan

Czerwińska

Mardari³

et al. 2022

Plants

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“…AD is a common long-term neurological disorder in the elderly, which is generally connected with the gradual decline in understanding, judgment, memory, and executive ability until complete loss. AD is known as the leading cause of death among old people worldwide (Zhang et al, 2022 ), and its great harmfulness brings heavy psychological pressure and economic burden to the families of patients. According to literature (Derby, 2020 ), the number of people suffering from AD and other dementias in the world currently exceeds 50 million, and the aging population further aggravates the rise of the patient population.…”

Section: Introductionmentioning

confidence: 99%

Constructing brain functional network by Adversarial Temporal-Spatial Aligned Transformer for early AD analysis

et al. 2022

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IntroductionThe brain functional network can describe the spontaneous activity of nerve cells and reveal the subtle abnormal changes associated with brain disease. It has been widely used for analyzing early Alzheimer's disease (AD) and exploring pathological mechanisms. However, the current methods of constructing functional connectivity networks from functional magnetic resonance imaging (fMRI) heavily depend on the software toolboxes, which may lead to errors in connection strength estimation and bad performance in disease analysis because of many subjective settings.MethodsTo solve this problem, in this paper, a novel Adversarial Temporal-Spatial Aligned Transformer (ATAT) model is proposed to automatically map 4D fMRI into functional connectivity network for early AD analysis. By incorporating the volume and location of anatomical brain regions, the region-guided feature learning network can roughly focus on local features for each brain region. Also, the spatial-temporal aligned transformer network is developed to adaptively adjust boundary features of adjacent regions and capture global functional connectivity patterns of distant regions. Furthermore, a multi-channel temporal discriminator is devised to distinguish the joint distributions of the multi-region time series from the generator and the real sample.ResultsExperimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) proved the effectiveness and superior performance of the proposed model in early AD prediction and progression analysis.DiscussionTo verify the reliability of the proposed model, the detected important ROIs are compared with clinical studies and show partial consistency. Furthermore, the most significant altered connectivity reflects the main characteristics associated with AD.ConclusionGenerally, the proposed ATAT provides a new perspective in constructing functional connectivity networks and is able to evaluate the disease-related changing characteristics at different stages for neuroscience exploration and clinical disease analysis.

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“…Many neurodegenerative illnesses, including AD, PD, and HD, have been linked to cholinergic system alterations, and the loss of cholinergic transmission, including acetylcholine (ACh), is crucial for cognitive function ( Hampel et al, 2018 ; Petrova et al, 2020 ; van der Zee et al, 2021 ; Bohnen et al, 2022 ). As a preferred pharmacophore of cholinesterase (ChE) inhibitors, carbamate fragments have been extensively exploited to produce extremely potent ChE inhibitors for the treatment of a wide range of ailments, including AD, HIV inhibitors, pesticides, and chemotherapeutic agents against various cancers ( Scheme 1B ) ( Matosevic and Bosak, 2020 ; Martins et al, 2021 ; Mishra et al, 2021 ; Zhang et al, 2022b ; Mdeni et al, 2022 ). This is mostly because of the structural properties of carbamate fragments, which can form bidentate H-bonds to anchor more firmly in the active pocket and act as an H-bond acceptor and donor.…”

Section: Introductionmentioning

confidence: 99%

From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders

Zhang

Wang

et al. 2022

Front. Pharmacol.

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A novel class of benzyl-free and benzyl-substituted carbamylated tryptamine derivatives (CDTs) was designed and synthesized to serve as effective building blocks for the development of novel multi-target directed ligands (MTDLs) for the treatment of neurological disorders linked to cholinesterase (ChE) activity. The majority of them endowed butyrylcholinesterase (BuChE) with more substantial inhibition potency than acetylcholinesterase (AChE), according to the full study of ChE inhibition. Particularly, hybrids with dibenzyl groups (2b-2f, 2j, 2o, and 2q) showed weak or no neuronal toxicity and hepatotoxicity and single-digit nanomolar inhibitory effects against BuChE. Through molecular docking and kinetic analyses, the potential mechanism of action on BuChE was first investigated. In vitro H2O2-induced HT-22 cells assay demonstrated the favorable neuroprotective potency of 2g, 2h, 2j, 2m, 2o, and 2p. Besides, 2g, 2h, 2j, 2m, 2o, and 2p endowed good antioxidant activities and COX-2 inhibitory effects. This study suggested that this series of hybrids can be applied to treat various ChE-associated neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), as well as promising building blocks for further structure modification to develop efficient MTDLs.

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Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease

Cited by 42 publications

References 275 publications

Exploring the Artemisia Genus: An Insight into the Phytochemical and Multi-Biological Potential of A. campestris subsp. lednicensis (Spreng.) Greuter & Raab-Straube

Exploring the Artemisia Genus: An Insight into the Phytochemical and Multi-Biological Potential of A. campestris subsp. lednicensis (Spreng.) Greuter & Raab-Straube

Constructing brain functional network by Adversarial Temporal-Spatial Aligned Transformer for early AD analysis

From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders

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