(2014) Indolinone-based acetylcholinesterase inhibitors: Synthesis, biological activity and molecular modeling. European Journal of Medicinal Chemistry. pp. 375-381.
![[img]](http://eprints.ssu.ac.ir/style/images/fileicons/text.png) |
Text
259.pdf Download (990kB) |
Abstract
A series of indolinone-based compounds bearing benzylpyridinium moiety was designed as dual-binding inhibitors of acetylcholinesterase (AChE). The target compounds 3a-u were synthesized by condensation of oxindole and pyridin-4-carbalehyde, and subsequent N-benzylation. The anti-cholinesterase activity evaluation of synthesized compounds revealed that most of them had very potent inhibitory activity against AChE, superior to standard drug donepezil. Particularly, 2-chlorobenzyl derivative 3c was the most potent compound against AChE with IC50 value of 0.44 nM, being 32-fold more potent than donepezil. Also, most of compounds were more potent than standard drug donepezil against butyrylcholinesterase (BuChE). Docking study revealed that the hydrophobic aromatic part (indoline) of representative compound 3c binds to the PAS and the N-benzylpyridinium residue binds to the CAS of AChE. © 2014 Elsevier Masson SAS. All rights reserved.
| Item Type: | Article |
|---|---|
| Keywords: | 1 (2 bromobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl) pyridinium chloride; 1 (2 chloro 6 fluorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (2 chlorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl) pyridinium chloride; 1 (2 fluorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl) pyridinium chloride; 1 (2 methylbenzyl) 4 ((2 oxoindolin 3 ylidene)methyl) pyridinium chloride; 1 (2 nitrobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl) pyridinium bromide; 1 (2,6 dichlorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (3 bromobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (3 chlorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl) pyridinium bromide; 1 (3 fluorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (3 methoxylbenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (3 methylbenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (4 bromobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (4 chlorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (4 fluorobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (4 methoxybenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (4 nitrobenzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium chloride; 1 (benzyl) 4 ((2 oxoindolin 3 ylidene)methyl)pyridinium bromide; 3 (pyridin 4 ylmethylene)indolin 2 one; acetylcholinesterase; benzyl derivative; cholinesterase; cholinesterase inhibitor; donepezil; indole derivative; oxindole; pyridin 4 carbalehyde; pyridine derivative; pyridinium derivative; unclassified drug; unindexed drug; 1 (2 bromobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (2 chloro 6 fluorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (2 chlorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (2 fluorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (2 methylbenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (2 nitrobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium bromide; 1 (2,4 dichlorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (2,6 dichlorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (3 bromobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (3 chlorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium bromide; 1 (3 fluorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (3 methoxybenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (3 methylbenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (3,4 dichlorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (4 bromobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (4 chlorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (4 chloromethylbenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (4 fluorobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (4 methoxybenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (4 nitrobenzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium chloride; 1 (benzyl) 4 (2 oxoindolin 3 ylidene)methylpyridinium bromide; acetylcholinesterase; cholinesterase; indolinone; cholinesterase inhibitor; indole derivative, article; benzylation; binding site; biological activity; blood brain barrier; catalytic anionic site; chemistry; cholinesterase inhibition; drug absorption; drug distribution; drug excretion; drug metabolism; drug penetration; drug potency; drug structure; drug synthesis; IC 50; in vitro study; molecular docking; molecular model; n benzylation; peripheral anionic site; Article; cholinesterase inhibition; IC50; chemical structure; dose response; metabolism; structure activity relation; synthesis, Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Indoles; Models, Molecular; Molecular Structure; Structure-Activity Relationship |
| Page Range: | pp. 375-381 |
| Journal or Publication Title: | European Journal of Medicinal Chemistry |
| Volume: | 84 |
| Publisher: | Elsevier Masson SAS |
| Depositing User: | ms soheila Bazm |
| URI: | http://eprints.ssu.ac.ir/id/eprint/8905 |
Actions (login required)
 |
View Item |