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dc.contributor.author | Ali S. | |
dc.contributor.author | Asad M.H.H.B. | |
dc.contributor.author | Khan F. | |
dc.contributor.author | Murtaza G. | |
dc.contributor.author | Rizvanov A.A. | |
dc.contributor.author | Iqbal J. | |
dc.contributor.author | Babak B. | |
dc.contributor.author | Hussain I. | |
dc.date.accessioned | 2021-02-25T21:01:16Z | |
dc.date.available | 2021-02-25T21:01:16Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 2314-6133 | |
dc.identifier.uri | https://dspace.kpfu.ru/xmlui/handle/net/162907 | |
dc.description.abstract | © 2020 Sayyad Ali et al. Proteases BACE1 (β-secretases) enzymes have been recognized as a promising target associated with Alzheimer's disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50=97±0.91 nM) and active to arrest (99%) β-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p<0.05). Improved pharmacokinetic parameters, viz., Log Po/w (1.76), Log S (-2.73), and better penetration to the brain (BBB permeation) with zero Lipinski violation, made it possible to hit the BACE1 as a potential therapeutic source for AD. | |
dc.relation.ispartofseries | BioMed Research International | |
dc.title | Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest β -Secretase Enzymatic Activity Involved in Alzheimer's Disease | |
dc.type | Article | |
dc.relation.ispartofseries-volume | 2020 | |
dc.collection | Публикации сотрудников КФУ | |
dc.source.id | SCOPUS23146133-2020-2020-SID85085588772 |