Xanthenone-based hydrazones as potent α-glucosidase inhibitors: Synthesis, solid state self-assembly and in silico studies

[Display omitted] •A new series of Xanthenone based hydrazones (5a–n) was synthesized.•New hydrazones were screened for their in vitro α-glucosidase inhibitory activity.•Structure activity relationship established.•In silico, molecular docking was carried out to study putative binding of potent hydr...

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Bibliographic Details
Published in:Bioorganic chemistry 2019-03, Vol.84, p.372-383
Main Authors: Tariq, Qamar-un-Nisa, Malik, Sana, Khan, Ajmal, Naseer, Muhammad Moazzam, Khan, Shafi Ullah, Ashraf, Abida, Ashraf, Muhammad, Rafiq, Muhammad, Mahmood, Khalid, Tahir, Muhammad Nawaz, Shafiq, Zahid
Format: Article
Language:English
Subjects:
Acarbose
alpha-Glucosidases - chemistry
alpha-Glucosidases - metabolism
Binding Sites
Catalytic Domain
Crystallography, X-Ray
Glycoside Hydrolase Inhibitors - chemical synthesis
Glycoside Hydrolase Inhibitors - metabolism
Hydrazone
Hydrazones - chemistry
Hydrazones - metabolism
Inhibitory Concentration 50
Molecular Conformation
Molecular Docking Simulation
Molecular docking study
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae Proteins - antagonists & inhibitors
Saccharomyces cerevisiae Proteins - metabolism
Structure-Activity Relationship
Xanthenes - chemistry
Xanthenone
α-glucosidase inhibitor
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Summary:[Display omitted] •A new series of Xanthenone based hydrazones (5a–n) was synthesized.•New hydrazones were screened for their in vitro α-glucosidase inhibitory activity.•Structure activity relationship established.•In silico, molecular docking was carried out to study putative binding of potent hydrazones with target enzyme.•Solid state self-assembly studies to explore the role of iminoamide dimer synthon in crystal packing. Xanthenone based hydrazone derivatives (5a–n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a–n) are characterized by their FTIR, 1H NMR, 13C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC50 = 375.38 ± 0.12 µM). Amongst the series, compound 5l (IC50 = 62.25 ± 0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2018.11.053