Discovery of a New Donepezil-like Acetylcholinesterase Inhibitor for Targeting Alzheimer’s Disease: Computational Studies with Biological Validation

Akhoon, Bashir Akhlaq; Choudhary, Sushil; Tiwari, Harshita; Kumar, Ajay; Barik, Manas Ranjan; Rathor, Laxmi; Pandey, Rakesh; Nargotra, Amit

doi:10.1021/acs.jcim.0c00496

Cited by 28 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Docking results for betanin, myricetin and folic acid indicated their minimal binding score (< -18) as compared to standard drug, donepezil ( Table 3 ). Previous in silico studies are in line with our study revealed the interaction of drugs with AChE not only elevate the acetylcholine levels but also reduce Aβ accumulation in Caenorhabditis elegans [ 37 ]. Our study depicts that few of phytochemicals are highly selective to their targeted enzyme.…”

Section: Discussionsupporting

confidence: 89%

The Insight of In Silico and In Vitro evaluation of Beta vulgaris phytochemicals against Alzheimer’s disease targeting acetylcholinesterase

et al. 2022

View full text Add to dashboard Cite

B. vulgaris extracts possess antioxidant, anti-inflammatory along with its role in improving memory disorders. Subsequently, in vitro and in silico studies of its purified phytochemicals may expand complementary and alternative Alzheimer’s therapeutic option. Super activation of acetylcholinesterase enzyme is associated explicitly with Alzheimer’s disease (AD) ultimately resulting in senile dementia. Hence, acetylcholinesterase enzyme inhibition is employed as a promising approach for AD treatment. Many FDA approved drugs are unable to cure the disease progression completely. The Present study was devised to explore the potential bioactive phytochemicals of B. vulgaris as alternative therapeutic agents against AD by conducting in vitro and in silico studies. To achieve this, chemical structures of phytochemicals were recruited from PubChem. Further, these compounds were analyzed for their binding affinities towards acetylcholinesterase (AChE) enzyme. Pharmacophoric ligand-based models showed major characteristics like, HBA, HBD, hydrophobicity, aromaticity and positively ionizable surface morphology for receptor binding. Virtual screening identified three hit compounds including betanin, myricetin and folic acid with least binding score compared to the reference drug, donepezil (-17 kcal/mol). Further, in vitro studies for anti-acetylcholinesterase activity of betanin and glycine betaine were performed. Dose response analysis showed 1.271 μM and 1.203 μM 50% inhibitory concentration (IC50) values for betanin and glycine betaine compounds respectively. Our findings indicate that phytoconstituents of B. vulgaris can be implicated as an alternative therapeutic drug candidate for cognitive disorders like Alzheimer’s disease.

show abstract

Section: Discussionsupporting

confidence: 89%

The Insight of In Silico and In Vitro evaluation of Beta vulgaris phytochemicals against Alzheimer’s disease targeting acetylcholinesterase

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Acetylcholinesterase is an enzyme that hydrolyzes acetylcholine, an essential neurotransmitter, at neuronal synapses, and at neuromuscular junctions, during signaling process [22]. In certain neurological disorders such as Alzheimer's disease (AD), acetyl cholinesterase is over activated in the synapses so that levels of acetylcholine in the brains is significantly diminished, which leads to weakened neurotransmission and thereby memory loss and other adverse effects [22].…”

Section: Discussionmentioning

confidence: 99%

Herbal snuff (AK-47 and HAM) induce oxidative stress and increase acetylcholinesterase enzyme activity in rat brain

Muhammad¹,

Barau²,

Zaruwa³

et al. 2021

GSC Biol. and Pharm. Sci.

View full text Add to dashboard Cite

Snuff has resurfaced not only in western countries but in Africa including Nigeria. It is now almost generally acceptable, among young and old in Nigeria. This research was designed to investigate the Effect of Hajiya Aisha Manpower (HAM) and AK-47 on Antioxidant Status and Acetylcholinesterase enzyme activity (AchE) of Wister Albino Rats. Thirty (30) Wister rats (110-120 g) were arbitrarily divided into five groups. Group1 (control); received only distilled water. Groups 2 and 3 (received 6 mg and 3 mg/kg b.w.t of HAM respectively). Groups 4 and 5 (received 6 mg and 3 mg/kg b.w.t AK-47 of respectively). After two months of treatments, the rats were anesthetized, blood samples were taken through heart puncture and brains of all rats were isolated and homogenized. The Result revealed Non-significant decrease in Superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and concomitant increase in GSH levels in treatment groups were observed in relation to the control. While a substantial increase (p˂ 0.5) in MDA was detected in treatment groups. Brain AchE activity increased significantly in all treatment groups in relation to the control. We conclude that Both AK-47 and HAM at high concentration induce oxidative stress, decreased antioxidant enzyme activities and promote degradation of acetylcholine in rat brain homogenate.

show abstract

“…Since we didn't have the human AChE protein, the purified enzyme from Electrophorus electricus (EeAChE) was chosen for the assay due to its relatively low cost compared to other sources. As the overall sequence identity and binding pocket sequence identity between these two proteins is very high (more than 88 % and 95 % respectively), EeAChE is often used as replacement for hAChE [36] in AChE inhibitory assays. Donepezil was used as the positive control.…”

Section: In Vitro Acetylcholinesterase (Ache) Inhibition Assaymentioning

confidence: 99%

Identification of 1,2,4‐Triazolylthioethanone Scaffold for the Design of New Acetylcholinesterase Inhibitors

Muhammad

Kumar

Wahab

et al. 2021

Molecular Informatics

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) inhibitors are the most effective drugs for Alzheimer's disease treatment. However, considering the potential and failure rates of AChE inhibitors, chemical scaffolds targeting cholinesterase specifically are still very limited. Herein, we report a new class of AChE inhibitors identified by employing a virtual screening approach that combines shape similarity with molecular docking calculations. Virtual screening followed by the evaluation of AChE inhibitory activity allowed us to identify 1,2,4-triazolylthioethanones as a novel class of AChE inhibitors. Thirteen compounds with 1,2,4-triazolylthiothanone core and IC 50 values in the range of 0.15 � 0.07 to 3.32 � 0.92 μM have been reported here. Our findings shed light into a class of AChE inhibitors that could be useful starting point for the development of novel therapeutics to tackle Alzheimer's disease.

show abstract

Discovery of a New Donepezil-like Acetylcholinesterase Inhibitor for Targeting Alzheimer’s Disease: Computational Studies with Biological Validation

Cited by 28 publications

References 31 publications

The Insight of In Silico and In Vitro evaluation of Beta vulgaris phytochemicals against Alzheimer’s disease targeting acetylcholinesterase

The Insight of In Silico and In Vitro evaluation of Beta vulgaris phytochemicals against Alzheimer’s disease targeting acetylcholinesterase

Herbal snuff (AK-47 and HAM) induce oxidative stress and increase acetylcholinesterase enzyme activity in rat brain

Identification of 1,2,4‐Triazolylthioethanone Scaffold for the Design of New Acetylcholinesterase Inhibitors

Contact Info

Product

Resources

About