Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

Muhammad Yar; Marek Bajda; Sohail Shahzad; Nisar Ullah; Mazhar Amjad Gilani; Muhammad Ashraf; Abdul Rauf; Ayesha Shaukat

doi:10.1016/j.bioorg.2014.11.006

Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

Bioorg Chem. 2015 Feb:58:65-71. doi: 10.1016/j.bioorg.2014.11.006. Epub 2014 Nov 21.

Authors

Muhammad Yar¹, Marek Bajda², Sohail Shahzad³, Nisar Ullah⁴, Mazhar Amjad Gilani⁵, Muhammad Ashraf⁶, Abdul Rauf⁷, Ayesha Shaukat⁶

Affiliations

¹ Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
² 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.
³ 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.
⁴ Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
⁵ Department of Chemical Engineering, COMSATS Institute of Information Technology, Lahore 54000, Pakistan.
⁶ Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁷ Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.

PMID: 25462626
DOI: 10.1016/j.bioorg.2014.11.006

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.

Keywords: Baker’s yeast; Diabetes; Imidazoles; Molecular modeling; Organocatalysis; α-glucosidase inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catalysis
Diabetes Mellitus / drug therapy*
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Glycoside Hydrolase Inhibitors / therapeutic use
Humans
Imidazoles / chemistry
Imidazoles / pharmacology*
Imidazoles / therapeutic use
Models, Molecular
Proton Magnetic Resonance Spectroscopy
Solvents / chemistry
Spectrometry, Mass, Electrospray Ionization
Spectroscopy, Fourier Transform Infrared
Structure-Activity Relationship

Substances

Glycoside Hydrolase Inhibitors
Imidazoles
Solvents