Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors

• Published in: European journal of medicinal chemistry 2017-09, Vol.138, p.396-406
• Main Authors: Nisa, Mehr-un, Munawar, Munawar A., Iqbal, Amber, Ahmed, Asrar, Ashraf, Muhammad, Gardener, Qurra-tul-Ann A., Khan, Misbahul A.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Alzheimer's disease; Animals; Butyrylcholinesterase; Butyrylcholinesterase - metabolism; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Citalopram - analogs & derivatives; Citalopram - chemical synthesis; Citalopram - chemistry; Citalopram - pharmacology; Dose-Response Relationship, Drug; Electrophorus; Enzyme inhibition; Escitalopram; Horses; Molecular Structure; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2017.06.036

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. [Display omitted] •Novel 5-(aroylhydrazinocarbonyl)escitalopram have been designed and synthesized.•5-(Aroylhydrazinocarbonyl)escitalopram screened for their inhibitory potential against cholinesterases (ChE).•In silico studies of 5-(aroylhydrazinocarbonyl)escitalopram have also been carried out.