title: Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors.
abstract: 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 ± 0.25 μM) and 2-methylphenyl- (70, IC50, 9.52 ± 0.23 μM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50 = 4.52 ± 0.17 μM) and 4-fluorophenyl- (78, IC50 = 5.31 ± 0.43 μM) 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 ΔG(bind) -6.42 and -6.93 kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity ΔG(bind) -9.04 and -8.51 kcal/mol, respectively, for BChE.
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
authors.lastname: Mehr-un-Nisa
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan. Electronic address: mamunawar.chem@pu.edu.pk.
authors.forename: Munawar A
authors.initials: MA
authors.lastname: Munawar
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
authors.forename: Fauzia A
authors.initials: FA
authors.lastname: Chattha
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
authors.forename: Samina
authors.initials: S
authors.lastname: Kousar
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan; Institute of Molecular Sciences & Bioinformatics, Lahore 54000, Pakistan.
authors.forename: Jawaria
authors.initials: J
authors.lastname: Munir
authors.affiliation: Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Tayaba
authors.initials: T
authors.lastname: Ismail
authors.affiliation: Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan; Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Misbahul A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D002800:Cholinesterase Inhibitors / Q000737:chemistry; D015283:Citalopram / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D014230:Triazoles; D015283:Citalopram
keywords: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase; Escitalopram; Triazoles