title: One-pot synthesis of tetrazole-1,2,5,6-tetrahydronicotinonitriles and cholinesterase inhibition: Probing the plausible reaction mechanism via computational studies.
abstract: In the present study, one-pot synthesis of 1H-tetrazole linked 1,2,5,6-tetrahydronicotinonitriles under solvent-free conditions have been carried out in the presence of tetra-n-butyl ammonium fluoride trihydrated (TBAF) as catalyst and solvent. Computational studies have been conducted to elaborate two plausible mechanistic pathways of this one-pot reaction. Moreover, the synthesized compounds were screened for cholinesterases (acetylcholinesterase and butyrylcholinesterase) inhibition which are consider to be major malefactors of Alzheimer's disease (AD) to find lead compounds for further research in AD therapy.
authors: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: abdul.hameed@iccs.edu.
authors: Abdul
authors: A
authors: Hameed
authors: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Syeda Tazeen
authors: ST
authors: Zehra
authors: Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors: Saba
authors: S
authors: Abbas
authors: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors: Riffat Un
authors: RU
authors: Nisa
authors: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors: Tariq
authors: T
authors: Mahmood
authors: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors: Khurshid
authors: K
authors: Ayub
authors: Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, 54600 Lahore, Pakistan.
authors: Mariya
authors: M
authors: Al-Rashida
authors: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmann str. 2, D-53113 Bonn, Germany.
authors: Jürgen
authors: J
authors: Bajorath
authors: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Khalid Mohammed
authors: KM
authors: Khan
authors: Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.
authors: Jamshed
authors: J
authors: Iqbal
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism*; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D009570:Nitriles; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 1,2,5,6-Tetrahydronicotinonitrile; Acetylcholinesterase (AChE); Butyrylcholinesterase (BChE); Click chemistry; Density Functional Theory (DFT); Ionic liquids; Tetrazole