التفاصيل البيبلوغرافية
| العنوان: |
Combining Virtual Screening Protocol and In Vitro Evaluation towards the Discovery of BACE1 Inhibitors |
| المؤلفون: |
Coimbra, Judite R. M., Baptista, Salete, Dinis, Teresa, Silva, Maria M. C., Moreira, Paula I., Santos, Armanda Emanuela Castro e, Salvador, Jorge A. R. |
| بيانات النشر: |
MDPI, 2020. |
| سنة النشر: |
2020 |
| مصطلحات موضوعية: |
Alzheimer’s disease (AD), amyloid- (A ), BACE1, small bioactive molecules, virtual screening, pharmacophore modelling, molecular docking, structure- and ligand-based methods, Amyloid Precursor Protein Secretases, Blood-Brain Barrier, Drug Evaluation, Preclinical, Ligands, Molecular Docking Simulation, Protease Inhibitors, Protein Conformation, User-Computer Interface |
| الوصف: |
The treatment options for a patient diagnosed with Alzheimer's disease (AD) are currently limited. The cerebral accumulation of amyloid-β (Aβ) is a critical molecular event in the pathogenesis of AD. When the amyloidogenic β-secretase (BACE1) is inhibited, the production of Aβ peptide is reduced. Henceforth, the main goal of this study is the discovery of new small bioactive molecules that potentially reach the brain and inhibit BACE1. The work was conducted by a customized molecular modelling protocol, including pharmacophore-based and molecular docking-based virtual screening (VS). Structure-based (SB) and ligand-based (LB) pharmacophore models were designed to accurately screen several drug-like compound databases. The retrieved hits were subjected to molecular docking and in silico filtered to predict their ability to cross the blood-brain barrier (BBB). Additionally, 34 high-scoring compounds structurally distinct from known BACE1 inhibitors were selected for in vitro screening assay, which resulted in 13 novel hit-compounds for this relevant therapeutic target. This study disclosed new BACE1 inhibitors, proving the utility of combining computational and in vitro approaches for effectively predicting anti-BACE1 agents in the early drug discovery process. |
| نوع الوثيقة: |
journal article |
| اللغة: |
English |
| العلاقة: |
2218-273X |
| DOI: |
10.3390/biom10040535 |
| الإتاحة: |
http://hdl.handle.net/10316/105820Test |
| حقوق: |
open access |
| رقم الانضمام: |
rcaap.com.uc.estudogeral.sib.uc.pt.10316.105820 |
| قاعدة البيانات: |
RCAAP |
