The exploration of novel Alzheimer’s therapeutic agents from the pool of FDA approved medicines using drug repositioning, enzyme inhibition and kinetic mechanism approaches - 09/12/18
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Graphical abstract |
Highlights |
• | Drug repositioning approach was used to predict the possible therapeutic effects of FDA approved drugs against AD disease. |
• | The screened drugs showed good binding interaction profiles within active region of AChE. |
• | Pharmacogenomics analysis depicted the possible associations between screened drugs and Alzheimer’s genes. |
• | Cinitapride showed a comparable results with standard and can be used as possible therapeutic agent in the treatment of AD. |
Abstract |
Novel drug development is onerous, time consuming and overpriced process with particularly low success and relatively high enfeebling rates. To overcome this burden, drug repositioning approach is being used to predict the possible therapeutic effects of FDA approved drugs in different diseases. Herein, we designed a computational and enzyme inhibitory mechanistic approach to fetch the promising drugs from the pool of FDA approved drugs against AD. The binding interaction patterns and conformations of screened drugs within active region of AChE were confirmed through molecular docking profiles. The possible associations of selected drugs with AD genes were predicted by pharmacogenomics analysis and confirmed through data mining. The stability behaviour of docked complexes (Drugs-AChE) were checked by MD simulations. The possible therapeutic potential of repositioned drugs against AChE were checked by in vitro analysis. Taken together, Cinitapride displayed a comparable results with standard and can be used as possible therapeutic agent in the treatment of AD.
Le texte complet de cet article est disponible en PDF.Keywords : Acetylcholinesterase, Drug-repositioning, Alzheimer’s disease, Molecular docking, Enzyme kinetics
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Vol 109
P. 2513-2526 - janvier 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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