title: Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes.
abstract: A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32±0.59 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland; Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan; Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Sohail
authors.initials: S
authors.lastname: Shahzad
authors.affiliation: Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
authors.forename: Nisar
authors.initials: N
authors.lastname: Ullah
authors.affiliation: Department of Chemical Engineering, COMSATS Institute of Information Technology, Lahore 54000, Pakistan.
authors.forename: Mazhar Amjad
authors.initials: MA
authors.lastname: Gilani
authors.affiliation: Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Rauf
authors.affiliation: Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Shaukat
mesh_terms: D002384:Catalysis; D003920:Diabetes Mellitus / Q000188:drug therapy*; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008958:Models, Molecular; D066244:Proton Magnetic Resonance Spectroscopy; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D007093:Imidazoles; D012997:Solvents
keywords: Baker’s yeast; Diabetes; Imidazoles; Molecular modeling; Organocatalysis; α-glucosidase inhibition