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Molecular modelling and synthesis of spiroimidazolidine-2,4-diones with dual activities as hypoglycemic agents and selective inhibitors of aldose reductase

Publication date:

September 2018


Source:Bioorganic Chemistry, Volume 79

Author(s): Manar G. Salem, Yasmine M. Abdel Aziz, Marwa Elewa, Hosam A. Elshihawy, Mohamed M. Said

Novel derivatives of spiroimidazolidinedione were synthesized and evaluated as hypoglycemic agents through binding to sulfonylurea receptor 1 (SUR1) in pancreatic beta-cells. Their selectivity index was calculated against both aldehyde reductase (ALR1) and aldose reductase (ALR2). Aldehyde reductase is a key enzyme in the polyol pathway that is involved in the etiology of the secondary diabetic complications. All structures were confirmed by microanalysis and by IR, 1H NMR, 13C NMR and EI-MS spectroscopy. The investigated compounds were subjected to molecular docking and an in silico prediction study to determine their free energy of binding (ΔG) values and predict their physicochemical properties and drug-likeness scores. Compound 1′-(5-chlorothiophene-2-ylsulfonyl)spiro[cyclohexane-1,5′-imidazolidine]-2′,4′-dione showed IC50 0.47 µM and 79% reduction in blood glucose level with a selectivity index 127 for ALR2.
Graphical abstract




Authors:   Author(s): Manar G. Salem, Yasmine M. Abdel Aziz, Marwa Elewa, Hosam A. Elshihawy, Mohamed M. Said
Journal:   Bioorganic Chemistry
Volume:   79
Year:   2018
Pages:   131
DOI:   10.1016/j.bioorg.2018.04.028
Publication date:   11-Jun-2018
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