title: A simple and efficient synthesis of novel inhibitors of alpha-glucosidase based on benzimidazole skeleton and molecular docking studies.
abstract: A novel series of benzimidazole derivatives were prepared starting from o-phenylenediamine and 4-nitro-o-phenylenediamine with iminoester hydrochlorides. Acidic proton in benzimidazole was exchanged with ethyl bromoacetate, then ethyl ester group was transformed into hydrazide group. Cyclization using CS2/KOH leads to the corresponding 1,3,4-oxadiazole derivative, which was treated with phenyl isothiocyanate resulted in carbothioamide group, respectively. As the target compounds, triazole derivative was obtained under basic condition and thiadiazole derivative was obtained under acidic condition from cyclization of carbothioamide group. Most reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. All compounds obtained in this study were investigated for α-glucosidase inhibitor activity. Compounds 6a, 8a, 4b, 5b, 6b and 7b were potent inhibitors with IC50 values ranging from 10.49 to 158.2μM. This has described a new class of α-glucosidase inhibitors. Molecular docking studies were done for all compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.
authors: Department of Chemistry, Recep Tayyip Erdogan University, 53100 Rize, Turkey. Electronic address: musa.ozil@erdogan.edu.tr.
authors: Musa
authors: M
authors: Özil
authors: Department of Chemistry, Recep Tayyip Erdogan University, 53100 Rize, Turkey.
authors: Mustafa
authors: M
authors: Emirik
authors: Department of Chemistry, Recep Tayyip Erdogan University, 53100 Rize, Turkey.
authors: Semiha Yılmaz
authors: SY
authors: Etlik
authors: Department of Biology, Recep Tayyip Erdogan University, 53100 Rize, Turkey.
authors: Serdar
authors: S
authors: Ülker
authors: Department of Nutrition and Dietetics, Faculty of Health Sciences, Karadeniz Technical University, Trabzon, Turkey.
authors: Bahittin
authors: B
authors: Kahveci
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D065089:Glycoside Hydrolase Inhibitors; D000520:alpha-Glucosidases
keywords: Benzimidazole; Microwave; Molecular docking; α-Glucosidase