title: Mannich-Benzimidazole Derivatives as Antioxidant and Anticholinesterase Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Study.
abstract: A series of Mannich bases of benzimidazole derivatives having a phenolic group were designed to assess their anticholinesterase and antioxidant activities. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds exhibited moderate to good AChE inhibitory activity (except for 2a), with IC50values ranging from 0.93 to 10.85 μM, and generally displayed moderate BuChE inhibitory activity. Also, most of the compounds were selective against BuChE. Compound 4b was the most active molecule on the AChE enzyme and also selective. In addition, we investigated the antioxidant effects of the synthesized compounds against FeCl2/ascorbic acid-induced oxidative stress in the rat brain in vitro, and the activity results showed that most of the compounds are effective as radical scavengers. Molecular docking studies and molecular dynamics simulations were also carried out.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University, Bornova, Izmir, Turkey.
authors.forename: Ayşe Selcen
authors.identifier: http://orcid.org/0000-0003-4412-3048
authors.initials: AS
authors.lastname: Alpan
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University, Bornova, Izmir, Turkey.
authors.forename: Görkem
authors.initials: G
authors.lastname: Sarıkaya
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University, Bornova, Izmir, Turkey.
authors.forename: Güneş
authors.initials: G
authors.lastname: Çoban
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University, Bornova, Izmir, Turkey.
authors.forename: Sülünay
authors.initials: S
authors.lastname: Parlar
authors.affiliation: Faculty of Pharmacy, Department of Biochemistry, Ege University, Bornova, Izmir, Turkey.
authors.forename: Güliz
authors.initials: G
authors.lastname: Armagan
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University, Bornova, Izmir, Turkey.
authors.forename: Vildan
authors.initials: V
authors.lastname: Alptüzün
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004593:Electrophorus; D005296:Ferrous Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006736:Horses; D008352:Mannich Bases / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001562:Benzimidazoles; D002800:Cholinesterase Inhibitors; D005296:Ferrous Compounds; D008352:Mannich Bases; D017382:Reactive Oxygen Species; C031000:benzimidazole; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D001205:Ascorbic Acid; C029451:ferrous chloride
keywords: Antioxidant activity; Benzimidazole; Cholinesterase inhibitors; Mannich bases; Molecular modeling