title: Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases.
abstract: To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12±0.01, 8.12±0.01 and 8.41±0.06μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85±0.0001μM). Three compounds 13, 24 and 3 having IC50 values 6.51±0.01, 9.22±0.07 and 37.82±0.14μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04±0.0001μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan. Electronic address: fazalstar@gmail.com.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Hayat
authors.initials: H
authors.lastname: Ullah
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: Department of Biohemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Muhammad Tariq
authors.initials: MT
authors.lastname: Javed
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Wajid
authors.initials: W
authors.lastname: Rehman
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Mohsan
authors.initials: M
authors.lastname: Nawaz
authors.affiliation: Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Sajid
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Farman
authors.initials: F
authors.lastname: Ali
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
authors.forename: Muhammad Naseem
authors.initials: MN
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D006834:Hydrazines; D012545:Schiff Bases; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Butyrylcholinesterase; Molecular docking; SAR; Schiff bases; Synthesis