title: Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors: characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity.
abstract: A series of novel carbonyl compounds was synthesized by a simple, eco-friendly and efficient method. These compounds were screened for anti-oxidant activity, in vitro cytotoxicity and for inhibitory activity for acetylcholinesterase and butyrylcholinesterase. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. Among them, compound 14 exhibited strong free radical scavenging activity (18.39 μM) while six compounds (1, 3, 4, 13, 14, and 19) were found to be the most protective against Aβ-induced neuronal cell death in PC12 cells. Compounds 4 and 14, containing N-methyl-4-piperidone linker, showed high acetylcholinesterase inhibitory activity as compared to reference drug donepezil. Molecular docking and QSAR (Quantitative Structure-Activity Relationship) studies were also carried out to determine the structural features that are responsible for the acetylcholinesterase and butyrylcholinesterase inhibitory activity.
authors: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. Electronic address: snab@pharmacy.ukm.my.
authors: Syed Nasir Abbas
authors: SN
authors: Bukhari
authors: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. Electronic address: ibj@pharmacy.ukm.my.
authors: Ibrahim
authors: I
authors: Jantan
authors: Department of Chemistry, Vidya Bharati Mahavidyalaya, Amravati, Maharashtra 444 602, India.
authors: Vijay H
authors: VH
authors: Masand
authors: Department of Chemistry, Vidya Bharati Mahavidyalaya, Amravati, Maharashtra 444 602, India.
authors: Devidas T
authors: DT
authors: Mahajan
authors: Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.
authors: Muhammad
authors: M
authors: Sher
authors: Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.
authors: M
authors: M
authors: Naeem-ul-Hassan
authors: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors: Muhammad Wahab
authors: MW
authors: Amjad
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055772:Green Chemistry Technology; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D007659:Ketones; D018696:Neuroprotective Agents; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 4-Piperidone; Alzheimer's disease; Neuroprotection; Oxidative stress; Synthesis