Citalopram is an antidepressant drug and cholinesterase inhibitor. Its S-enantiomer is very active in its action than R- enantiomers. Citalopram metabolizes into its desmethylescitalopram (4) and didesmethylescitalopram (5) metabolites, mediated by various cytochromes. Acetylcholinesterase is an enzyme that lyses the neurotransmitter acetylcholine into acetic acid and choline in brain. Absence of these neurotransmitters can cause serious diseases like dementia, anxiety attacks and Alzheimer’s disease. Citalopram and its metabolites act as cholinesterase inhibitors and make neurotransmitter available in brain by antagonizing the effect of cholinesterase. Desmethylescitalopram (4) is prepared by functionalizing escitalopram. Desmethylescitalopram analogues (40-41)
were prepared by refluxing this intermediate (4) with aromatic and aliphatic ketones. These compounds (40-41) are characterized by FTIR, UV, GC-MS and MS-ESI
spectroscopic analyses. Furthermore their biological activity is checked by structure and activity relationship (SAR). Novelty of the work is to investigate that to what extent the two derivatives (40) and (41) show cholinesterase activity. Structure and activity
relationship (SAR) revealed that the compound (40) showed best %age cholinesterase inhibition (93.51±0.51, 84.09±0.34) with IC50 (μM) values of (1.80±0.11, 2.11±0.31) for AChE and BChE respectively. The compound (41) showed comparatively less %age inhibition (86.07±0.15, 84.01±0.41) with IC50 (μM) value of (5.71±0.32, 3.90±0.66) for AChE and BChE respectively. But collectively both compounds showed best
cholinesterase inhibition as compared to desmethylescitalopram (4) showing %age inhibition (85.15±0.19, 85.52±0.63) with IC50 (μM) value of (7.81±0.33, 5.88±0.27) for AChE and BChE respectively. Concluding these two derivatives depicted good cholinesterase inhibition.