title: Synthesis, characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors.
abstract: Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as (1)H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC50<10 μM. The highest inhibitory activity (IC50=5.12 μM for AChE and IC50=8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure-activity relationship was discussed.
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia. kyyeong@gmail.com
authors.forename: Yeong Keng
authors.initials: YK
authors.lastname: Yoon
authors.forename: Mohamed Ashraf
authors.initials: MA
authors.lastname: Ali
authors.forename: Ang Chee
authors.initials: AC
authors.lastname: Wei
authors.forename: Tan Soo
authors.initials: TS
authors.lastname: Choon
authors.forename: Kooi-Yeong
authors.initials: KY
authors.lastname: Khaw
authors.forename: Vikneswaran
authors.initials: V
authors.lastname: Murugaiyah
authors.forename: Hasnah
authors.initials: H
authors.lastname: Osman
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Masand
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D002800:Cholinesterase Inhibitors; C031000:benzimidazole; D002802:Cholinesterases
keywords: Acetylcholinesterase; Alzheimer’s Disease; Benzimidazoles; Butyrylcholinesterase; ULPRGUULPLUDKL-UHFFFAOYSA-N