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 |
|