title: Ethyl nitrobenzoate: A novel scaffold for cholinesterase inhibition.
abstract: A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia; School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway, 47500 Selangor, Malaysia. Electronic address: Yeong.KengYoon@monash.edu.
authors.forename: Keng Yoon
authors.initials: KY
authors.lastname: Yeong
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
authors.forename: Wai-Lam
authors.initials: WL
authors.lastname: Liew
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
authors.forename: Vikneswaran
authors.initials: V
authors.lastname: Murugaiyah
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
authors.forename: Chee Wei
authors.initials: CW
authors.lastname: Ang
authors.affiliation: Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
authors.forename: Hasnah
authors.initials: H
authors.lastname: Osman
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
authors.forename: Soo Choon
authors.initials: SC
authors.lastname: Tan
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus; D006801:Humans; D062105:Molecular Docking Simulation; D009579:Nitrobenzoates / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D009579:Nitrobenzoates; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Ethyl nitrobenzoate