Green synthesis, inhibition studies of yeast α-glucosidase and molecular docking of pyrazolylpyridazine amines

Faryal Chaudhry; Abdul Qayuum Ather; Mohammad Javaid Akhtar; Ayesha Shaukat; Mohammad Ashraf; Mariya Al-Rashida; Munawar Ali Munawar; Misbahul Ain Khan

doi:10.1016/j.bioorg.2017.02.003

Green synthesis, inhibition studies of yeast α-glucosidase and molecular docking of pyrazolylpyridazine amines

Bioorg Chem. 2017 Apr:71:170-180. doi: 10.1016/j.bioorg.2017.02.003. Epub 2017 Feb 9.

Authors

Faryal Chaudhry¹, Abdul Qayuum Ather², Mohammad Javaid Akhtar³, Ayesha Shaukat⁴, Mohammad Ashraf⁵, Mariya Al-Rashida⁶, 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. Electronic address: frylchaudhry@yahoo.com.
² Applied Chemistry Research Center, PCSIR Laboratories Complex, Lahore, Pakistan.
³ Department of Chemistry, Stony Brook University, Long Island, NY 11794-3400, USA.
⁴ Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁵ Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁶ Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan.
⁷ Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
⁸ Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan; Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.

PMID: 28259376
DOI: 10.1016/j.bioorg.2017.02.003

Abstract

An efficient and environmentally benign simple fusion reaction of 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (1a) or 3-chloro-6-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)pyridazine (2a) with different aliphatic/aromatic amines have produced a series of novel pyrazolylpyridazine amines (4a-4c &5a-5m). All compounds exhibited moderate in vitro yeast α-glucosidase inhibition except m-chloro derivative 5g, which was found potent inhibitor of this enzyme with IC₅₀ value of 19.27±0.005µM. The molecular docking further helped in understanding the structure activity relationship of these compounds including 5g.

Keywords: Docking; Green chemistry; Nucleophilic substitution; Pyrazolylpyridazine amines; α-Glucosidase inhibitors.

MeSH terms

Amination
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry*
Glycoside Hydrolase Inhibitors / pharmacology*
Green Chemistry Technology / methods
Molecular Docking Simulation
Pyridazines / chemical synthesis
Pyridazines / chemistry*
Pyridazines / pharmacology*
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / drug effects
Saccharomyces cerevisiae / enzymology*
Structure-Activity Relationship
alpha-Glucosidases / chemistry
alpha-Glucosidases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
Pyridazines
alpha-Glucosidases