Screening and analysis of acetyl-cholinesterase (AChE) inhibitors in the context of Alzheimer's disease
| Autor: | Mohd Babu Khan, Naidu Subbarao, Dinakara Rao Ampasala, Bhagath Kumar Palaka, Tuleshwori Devi Sapam |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Binding free energy Aché Stereochemistry 03 medical and health sciences Hydrolase medicine Galantamine chemistry.chemical_classification Virtual screening MD simulations Chemistry General Medicine Hypothesis FEL analysis language.human_language CNS-BBB database 030104 developmental biology Enzyme Virtual Screening Docking (molecular) Tacrine language AChE Acetylcholine medicine.drug |
| Zdroj: | Bioinformation |
| ISSN: | 0973-2063 |
| Popis: | Acetyl-cholinesterase enzyme (AChE) is a known target for identifying potential inhibitors against Alzheimer diseases (AD). Therefore, it is of interest to screen AChE with the CNS-BBB database. An AChE enzyme is a member of hydrolase family is activated by acetylcholine (ACh), so, targeting the AChE enzyme with the potential inhibitor may block the binding of the ACh. In this study we carried out virtual screening of drug-like molecules from Chemical Diversity Database particularly CNS-BBB compounds, to identify potential inhibitors using Glide docking program. Top ranking ten compounds, which have lower Glide Score when compared to known drugs (Tacrine and Galantamine) for AChE. For top three molecules MD simulation was carried out and calculated binding free energy. We report the best binding compounds with AChE compared to known drugs (Taine and Galantamine) for AD. We further document the salient features of their molecular interaction with the known target. Three molecules (1-benzyl-3-(2- hydroxyethyl)-N-[2-(3-pyridyl)ethyl]-3-pyrrolidinecarboxamide, N-{3[benzyl(methyl)amino]propyl}-1,5-dimethyl-4-oxo-4,5-dihydro- 1H-pyrrolo[3,2-c]quinoline-2-carboxamide, and 6-chloro-N-[2-(diethylamino)-2-phenylethyl]-4-oxo-4H-chromene-2-carboxamide) have -196.36, -204.27, -214.40 kJ/mol, binding free energy values respectively which are much lower than values calculated for the reference ligands Tacrine and Galantamine having -119.65 and -142.18 kJ/mol respectively. Thus these molecules can be very novel potential inhibitors against AChE involved in Alzheimer's disease. |
| Databáze: | OpenAIRE |
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