Citalopram (1) is an antidepressant drug and acts as cholinesterase inhibitor. It exists in two enantiomeric forms that are R-Citalopram (3) and S-Citalopram (2). The S-enantiomer is
biologically active and is known as Escitalopram (2). Citalopram (1) is metabolized to desmethylescitlopram (4) and didesmethylescitalopram (5) by three hepatic enzymes. Citalopram (1) and its metabolites antagonize the cholinesterase activity thus relaying acetylcholine for transmission of nerve impulse. Didesmethylescitalopram
(5) was prepared by didesmethylation of Escitalopram (2). Analogues of didesmethyescitalopram (36 & 37) were prepared by the reaction of didesmethylcitalopram (5) with ethyl methyl ketone and benzophenone respectively. The intermediate (5) and analogues (36 and 37) were analyzed and characterized by Ultraviolet spectrophotometer (UV), Forier transform spectrophotometer (FTIR) and Mass Spectrophotometer (Electron spray ionization) MS (ESI). Compounds (36 and 37) also showed inhibition of cholinesterase activity. Didesmethylescitalopram (5) showed percentage inhibition
of 89.15 ±0.19 and 87.52 ±0.63 with IC50 values of 6.85 ±0.33μM and 4.08 ±0.27μM for acetylcholinesterase and butyrylcholinesterase respectively. The compound 36 depicted
95.51±0.51% (IC50, 1.09μM) AChE inhibition while 90.09±0.34% (IC50, 1.11±0.31μM) BChE inhibition. Likewise, compound 37 showed 90.07±0.15% (IC50, 3.71±0.32μM) AChE inhibition while 88.01±0.41 (IC50, 2.90±0.66μM) BChE inhibition. So, compound 36 is the most potent compound of the series possessing highest cholinesterase inhibition.