In vitro anti-acetylcholinesterase activity of an aqueous extract of Unicaria tomentosa and in silico study of its active constituents

Chowdhury, Suman; Shivani, .; Kumar, Suresh

doi:10.6026/97320630012112

Cited by 9 publications

(9 citation statements)

References 14 publications

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“…The important water molecules found to be interacting with the active site residues of the enzyme were retained. In case of 4EY6, seven water molecules [ 37 ]; for 1POM, two water molecules [ 38 ]; two water molecule in 4D8C, one in 3L5E [ 39 ] and one in 1PBQ [ 40 ]. No water molecules were retained in 2Z5X [ 41 ].…”

Section: Methodsmentioning

confidence: 99%

In silico repurposing of antipsychotic drugs for Alzheimer’s disease

2017

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BackgroundAlzheimer’s disease (AD) is the most prevalent form of dementia and represents one of the highest unmet requirements in medicine today. There is shortage of novel molecules entering into market because of poor pharmacokinetic properties and safety issues. Drug repurposing offers an opportunity to reinvigorate the slowing drug discovery process by finding new uses for existing drugs. The major advantage of the drug repurposing approach is that the safety issues are already investigated in the clinical trials and the drugs are commercially available in the marketplace. As this approach provides an effective solution to hasten the process of providing new alternative drugs for AD, the current study shows the molecular interaction of already known antipsychotic drugs with the different protein targets implicated in AD using in silico studies.ResultA computational method based on ligand–protein interaction was adopted in present study to explore potential antipsychotic drugs for the treatment of AD. The screening of approximately 150 antipsychotic drugs was performed on five major protein targets (AChE, BuChE, BACE 1, MAO and NMDA) by molecular docking. In this study, for each protein target, the best drug was identified on the basis of dock score and glide energy. The top hits were then compared with the already known inhibitor of the respective proteins. Some of the drugs showed relatively better docking score and binding energies as compared to the already known inhibitors of the respective targets. Molecular descriptors like molecular weight, number of hydrogen bond donors, acceptors, predicted octanol/water partition coefficient and percentage human oral absorption were also analysed to determine the in silico ADME properties of these drugs and all were found in the acceptable range and follows Lipinski’s rule.ConclusionThe present study have led to unravel the potential of leading antipsychotic drugs such as pimozide, bromperidol, melperone, anisoperidone, benperidol and anisopirol against multiple targets associated with AD. Benperidol was found to be the best candidate drug interacting with different target proteins involved in AD.

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Section: Methodsmentioning

confidence: 99%

In silico repurposing of antipsychotic drugs for Alzheimer’s disease

2017

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“…Water molecules and other heteroatoms were removed using Discovery Studio 2019 to avoid docking interference. Hydroalcoholic extract of M. pudica and its fractions were tested for in-vitro AChE activity as explained by Chowdhury S et al [21] . Donepezil was taken as standard and suitable controls for all tests.…”

Section: In Silico and In Vitro Ache Inhibitory Activitymentioning

confidence: 99%

Network pharmacology-based prediction and experimental validation of Mimosa pudica for Alzheimer's disease

Duyu¹,

Khatib²,

Khanal³

et al. 2020

J Phytopharmacol

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Mimosa pudica is a traditional folk medicine and has been reported to improve the memory in experimentally induced amnesia. However, present literature lacks the data for M. pudica compoundprotein interaction with targets related to Alzheimer's disease (AD) including cytotoxic profile. Hence, the present study aims to evaluate in silico and in vitro antioxidant, cytotoxicity, and acetylcholinesterase inhibitory activity and network evaluation of M. pudica with targets related to Alzheimer's disease. The whole plant of M. pudica was collected, authenticated and hydroalcoholic extract/fractions were prepared. The antioxidant activity of the hydroalcoholic extract was evaluated by DPPH֗ free radical scavenging assay (in vitro) and xanthine oxidase binding affinity (in silico). Acetylcholinesterase (AChE) inhibitors from M. pudica were identified from an open-source database and analyzed using a network among compounds, proteins, and modulated pathways. Docking was performed using autodock4 and AChE inhibitory activity of extract/fraction(s) was carried using the in vitro method. The cytotoxicity of M. pudica was assessed using CLC-Pred (in silico) and MTT assay (in vitro). Quercetin-3-O-β-Dxylopyranoside and myricetin-3-O-β-D-xylopyranoside showed the highest binding affinity with xanthine oxidase. AChE was majorly targeted by multiple phytoconstituents of M. pudica. Quercetin showed the highest binding affinity with AChE. Luteolin interacted with maximum proteins involved in the pathogenesis of AD. The compounds were predicted to be more cytotoxic in cancer cells compared to normal. The phytoconstituents from M. pudica were found to be safe in normal cells, and were potent antioxidants. Flavonoids showed highest binding affinity with xanthine oxidase and fraction rich in flavonoids showed the highest AChE inhibitory capacity.

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“…Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia [ 1 ]. AD is characterized by an insidious decrease or loss in memory, personality alteration, and decline of cognitive and non-cognitive functions, which thoroughly leads to disabling of the patient [ 2 ].…”

Section: Introductionmentioning

confidence: 99%