Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors.
Eur J Med Chem
; 138: 396-406, 2017 Sep 29.
Article
in En
| MEDLINE
| ID: mdl-28688279
ABSTRACT
A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58-84) have been designed, synthesized and tested for their inhibitory potential against cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound of this series having IC50 1.80 ± 0.11 µM for acetylcholinesterase (AChE) inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76) was the most active compound of the series with IC50 2.11 ± 0.31 µM. Structure-activity relationship illustrated that mild electron donating groups enhanced enzyme inhibition while electron withdrawing groups reduced the inhibition except o-NO2. However, size and position of the substituents affected enzyme inhibitions. . In docking study of AChE, the ligands 71, 72 and 76 showed the scores of 5874, 5756 and 5666 and ACE of -64.92,-203.25 and -140.29 kcal/mol, respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016, 6150 and 5994 with ACE values -170.91, -256.84 and -235.97 kcal/mol, respectively.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Acetylcholinesterase
/
Butyrylcholinesterase
/
Citalopram
/
Cholinesterase Inhibitors
Limits:
Animals
Language:
En
Year:
2017
Type:
Article