A novel serie of escitalopram triazoles (60-88) and a tetrazole (89) have been synthesized and subjected to a study to establish the inhibitory potential of these compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some selectivity in inhibition has been observed. The 4-chlorophenyl- (75, IC50, 6.71+/-0.25muM) and 2-methylphenyl- (70, IC50, 9.52+/-0.23muM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50=4.52+/-0.17muM) and 4-fluorophenyl- (78, IC50=5.31+/-0.43muM) have found to be excellent BChE inhibitors. It has also been observed that ortho, meta and para substituted electron donating groups increase the inhibition, while electron withdrawing groups reduce the inhibition. Docking analyses of inhibitors with AChE have depicted the binding energies for 70 and 75 as DeltaGbind -6.42 and -6.93kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity DeltaGbind -9.04 and -8.51kcal/mol, respectively, for BChE.
        
Related information
Citations formats
Mehr Un N, Munawar MA, Chattha FA, Kousar S, Munir J, Ismail T, Ashraf M, Khan MA (2015) Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors Bioorganic & Medicinal Chemistry23: 6014-24
Mehr Un N, Munawar MA, Chattha FA, Kousar S, Munir J, Ismail T, Ashraf M, Khan MA (2015) Bioorganic & Medicinal Chemistry23: 6014-24