Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening

Liu, Guangpu; Jiao, Yang; Lin, Yanping; Hao, Haifang; Dou, Yanli; Yang, Juan; Jiang, Cheng‐Shi; Chang, Ping

doi:10.1248/cpb.c19-00927

Cited by 4 publications

(3 citation statements)

References 33 publications

(33 reference statements)

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“…Kumarasiri M et al reported by virtual screening that seven drug-like molecules, identified as potential cyclin-dependent kinase (CDK) 8 inhibitors, were active against colorectal cancer cell lines [26]. Another virtual screening model was established to successfully find acetylcholinesterase (AChE) inhibitors with the ability of protecting human neuroblastoma cells from Aβ-induced injury for Alzheimer's disease treatment [27]. Furthermore, in the onset of the COVID-19 pandemic, there was a strong interest in rapidly and economically finding effective anti-coronavirus agents.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays

Chen

Chi

Zhang

et al. 2023

IJMS

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The Zika virus (ZIKV) epidemic poses a significant threat to human health globally. Thus, there is an urgent need for developing effective anti-ZIKV agents. ZIKV non-structural protein 5 RNA-dependent RNA polymerase (RdRp), a viral enzyme for viral replication, has been considered an attractive drug target. In this work, we screened an anti-infection compound library and a natural product library by virtual screening to identify potential candidates targeting RdRp. Then, five selected candidates were further applied for RdRp enzymatic analysis, cytotoxicity, and binding examination by SPR. Finally, posaconazole (POS) was confirmed to effectively inhibit both RdRp activity with an IC50 of 4.29 μM and the ZIKV replication with an EC50 of 0.59 μM. Moreover, POS was shown to reduce RdRp activity by binding with the key amino acid D666 through molecular docking and site-directed mutation analysis. For the first time, our work found that POS could inhibit ZIKV replication with a stronger inhibitory activity than chloroquine. This work also demonstrated fast anti-ZIKV screening for inhibitors of RdRp and provided POS as a potential anti-ZIKV agent.

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Section: Discussionmentioning

confidence: 99%

Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays

Chen

Chi

Zhang

et al. 2023

IJMS

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“…Butyrylcholinesterase (BuChE) has also had a great effect on the advancement of AD. BuChE inhibitors could retrieve cholinergic activity via restoring the proportions of AChE/BuChE activity like in a normal brain ( Liu et al, 2020 ). As a consequence, dual AChE/BuChE inhibitors have drawn great interest in the management of AD ( Davidsson et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Coumarin–Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer’s Disease

et al. 2022

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In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2–144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9–123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce β-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.

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“…These biochemical reactions are very vital to allow a cholinergic neuron to return to its normal resting state after activation [ 11 ]. For example, acetylcholine at a motor enclave triggers muscle contraction, for the muscle to relax afterward cholinesterase has to act to neutralize acetylcholine rather than remaining locked in a tense state [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model

Hassan

Ibrahim

Yusuf

et al. 2020

Journal of Toxicology

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Background. Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed. Methods. The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC). Results. The result shows activities with high significant differences at P<0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method. Conclusion. The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements.

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Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening

Cited by 4 publications

References 33 publications

Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays

Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays

Novel Coumarin–Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer’s Disease

Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model

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