An In Silico Study Based on QSAR and Molecular Docking and Molecular Dynamics Simulation for the Discovery of Novel Potent Inhibitor against AChE DOI Creative Commons

Meriem Khedraoui,

Oussama Abchır, Hassan Nour

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(7), P. 830 - 830

Published: June 25, 2024

Acetylcholinesterase (AChE) is one of the main drug targets for treating Alzheimer’s disease. This current study relies on multiple molecular modeling approaches to develop new potent inhibitors AChE. We explored a 2D QSAR using statistical method linear regression based set substituted 5-phenyl-1,3,4-oxadiazole and N-benzylpiperidine analogs, which were recently synthesized proved their inhibitory activities against acetylcholinesterase (AChE). The descriptors, polar surface area, dipole moment, weight are key structural properties governing AChE inhibition activity. MLR model was selected its parameters: R2 = 0.701, R2test 0.76, Q2CV 0.638, RMSE 0.336, demonstrating predictive reliability. Randomization tests, VIF applicability domain tests adopted verify model’s robustness. As result, 11 molecules designed with higher anti-Alzheimer’s than molecule. demonstrated improved pharmacokinetic through an in silico ADMET study. A docking conducted explore mechanisms binding affinities active site. scores compounds M1, M2, M6 (−12.6 kcal/mol), (−13 (−12.4 respectively, standard inhibitor Donepezil score (−10.8 kcal/mol). Molecular dynamics simulations over 100 ns used validate results, indicating that M1 M2 remain stable site, confirming potential as promising anti-AChE inhibitors.

Language: Английский

Quinoline–sulfonamides as a multi-targeting neurotherapeutic for cognitive decline:in vitro,in silicostudies and ADME evaluation of monoamine oxidases and cholinesterases inhibitors DOI Creative Commons
Saquib Jalil, Zahid Hussain,

Syed Mobashir Ali Abid

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(13), P. 8905 - 8920

Published: Jan. 1, 2024

Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder with multiple enzymes involved.

Language: Английский

Citations

9
Identification of acetylcholinesterase inhibitors from traditional medicinal plants for Alzheimer's disease using in silico and machine learning approaches DOI Creative Commons
Md. Tarikul Islam, Md. Aktaruzzaman,

Ahmed Saif

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(47), P. 34620 - 34636

Published: Jan. 1, 2024

Acetylcholinesterase (AChE) holds significance in Alzheimer's disease (AD), where cognitive impairment correlates with insufficient acetylcholine levels. AChE's role involves the breakdown of acetylcholine, moderating cholinergic neuron activity to prevent overstimulation and signal termination. Hence, inhibiting AChE emerges as a potential treatment avenue for AD. A library 2500 compounds, derived from 25 traditionally used medicinal plants, was constructed using IMPAAT database traditional plants. The canonical SMILES these compounds were collected underwent virtual screening based on physicochemical properties, subsequent determination IC

Language: Английский

Citations

9
MicroRNAs and synapse turnover in Alzheimer’s disease DOI

Sarthak Dalal,

Jaime Ramirez-Gomez, Bhupender Sharma

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102377 - 102377

Published: June 12, 2024

Language: Английский

Citations

8
The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses DOI Creative Commons
Elana R. Lockshin, Nicole Calakos

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 87, P. 102886 - 102886

Published: June 19, 2024

The integrated stress response (ISR) is a highly conserved biochemical pathway that regulates protein synthesis. ISR activated in to diverse stressors restore cellular homeostasis. As such, the implicated wide range of diseases, including brain disorders. However, brain, also has potent influence on processes beyond proteostasis, namely synaptic plasticity, learning and memory. Thus, setting activity may have dual effects proteostasis function. In this review, we consider ISR's contribution disorders through lens its potential plasticity. From these examples, illustrate at times be "double-edged sword". We highlight as therapeutic target improve circuit function diseases independent role disease pathogenesis.

Language: Английский

Citations

8
An In Silico Study Based on QSAR and Molecular Docking and Molecular Dynamics Simulation for the Discovery of Novel Potent Inhibitor against AChE DOI Creative Commons

Meriem Khedraoui,

Oussama Abchır, Hassan Nour

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(7), P. 830 - 830

Published: June 25, 2024

Acetylcholinesterase (AChE) is one of the main drug targets for treating Alzheimer’s disease. This current study relies on multiple molecular modeling approaches to develop new potent inhibitors AChE. We explored a 2D QSAR using statistical method linear regression based set substituted 5-phenyl-1,3,4-oxadiazole and N-benzylpiperidine analogs, which were recently synthesized proved their inhibitory activities against acetylcholinesterase (AChE). The descriptors, polar surface area, dipole moment, weight are key structural properties governing AChE inhibition activity. MLR model was selected its parameters: R2 = 0.701, R2test 0.76, Q2CV 0.638, RMSE 0.336, demonstrating predictive reliability. Randomization tests, VIF applicability domain tests adopted verify model’s robustness. As result, 11 molecules designed with higher anti-Alzheimer’s than molecule. demonstrated improved pharmacokinetic through an in silico ADMET study. A docking conducted explore mechanisms binding affinities active site. scores compounds M1, M2, M6 (−12.6 kcal/mol), (−13 (−12.4 respectively, standard inhibitor Donepezil score (−10.8 kcal/mol). Molecular dynamics simulations over 100 ns used validate results, indicating that M1 M2 remain stable site, confirming potential as promising anti-AChE inhibitors.

Language: Английский

Citations

8