In search of new α-glucosidase inhibitors: Imidazolylpyrazole derivatives

Faryal Chaudhry; Sadia Naureen; Rahila Huma; Ayesha Shaukat; Mariya Al-Rashida; Nadia Asif; Mohammad Ashraf; Munawar Ali Munawar; Misbahul Ain Khan

doi:10.1016/j.bioorg.2017.01.017

In search of new α-glucosidase inhibitors: Imidazolylpyrazole derivatives

Bioorg Chem. 2017 Apr:71:102-109. doi: 10.1016/j.bioorg.2017.01.017. Epub 2017 Jan 23.

Authors

Faryal Chaudhry¹, Sadia Naureen², Rahila Huma³, Ayesha Shaukat⁴, Mariya Al-Rashida⁵, Nadia Asif², Mohammad Ashraf⁶, Munawar Ali Munawar⁷, Misbahul Ain Khan⁸

Affiliations

¹ Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan; Department of Chemistry, Kinnaird College for Women, Lahore 54000, Pakistan.
² Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
³ Department of Chemistry, Kinnaird College for Women, Lahore 54000, Pakistan.
⁴ Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁵ Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan.
⁶ Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁷ Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan. Electronic address: mamunawar.chem@pu.edu.pk.
⁸ Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan; Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.

PMID: 28160945
DOI: 10.1016/j.bioorg.2017.01.017

Abstract

Under three different reaction conditions (conventional heating, microwave irradiations and amino acid catalysis), a series of imidazolylpyrazoles (2a-2k) were synthesized in good to excellent yields from a mixture of three precursors: aryl(hetaryl)pyrazole-4-carbaldehydes (1a-1k), benzil and ammonium acetate. α-Glucosidase inhibition assay revealed a new class of highly potent agents wherein each compound displayed significant inhibitory potentials (in terms of percentage inhibition and relative IC₅₀ values) as compared to that of the reference drug (Acarbose). Moreover, molecular modelling of most potent compounds 2h, 2j and 2k also helped in understanding the structure and activity relationship.

Keywords: Diabetes; Docking; Imidazolylpyrazoles; Multicomponent reaction; α-Glucosidase inhibition.

MeSH terms

Diabetes Mellitus, Type 2 / drug therapy
Diabetes Mellitus, Type 2 / enzymology
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry*
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Molecular Docking Simulation
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / pharmacology*
Saccharomyces cerevisiae / drug effects
Saccharomyces cerevisiae / enzymology*
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
Pyrazoles
alpha-Glucosidases