Synthesis, characterization, hypoglycemic and aldose reductase inhibition activity of arylsulfonylspiro[fluorene-9,5′-imidazolidine]-2′,4′-diones

A series of 3-arylsulfonylspiroimidazolidine-2,4-diones (2a-g) and their corresponding rearranged products, 1-arylsulfonylspiroimidazolidine-2,4-diones (3a-g) were synthesized and evaluated for antidiabetic and aldose reductase inhibition activity. Three of the compounds (2b, 2c and 3c) were found more potent in-vivo hypoglycemic agents than the commercial drug glibenclamide. The free energy of binding (ΔG) values showed that the compounds are active against aldose reductase and aldehyde reductase enzymes, which was also estimated using molecular mechanics Poisson-Boltzmann surface area method. Of the tested compounds, 2b was found to be the most potent in-vitro selective inhibitor of ALR2 possessing an IC50 value of 0.89 μm. Structure activity relationship and molecular docking revealed the importance of substitution features of aryl group of aryllsulfonylimidazolidine-2,4-dione scaffold. It was observed that the substitution with a halogen at para position of the aryl group had a remarkable effect on ALR2 inhibition potency. Three of the synthesized sulfonyclyclic urea derivatives were found more potent in-vivo hypoglycemic agents than glibenclamide. In in-vitro ARI assay, the compounds 3a-g were found more ACR1 inhibitors than the standard. [Display omitted] •Two series of sulfonylcyclic ureas (2a-g and 3a-g) were successfully synthesized.•The compounds were evaluated for hypoglycemic and ARI activity.•Compounds 2b, 2c and 3c were more potent hypoglycemic agents than glibenclamide.•The compounds are more active against aldose reductase than aldehyde reductase.•Compound 2b was found most potent selective inhibitor of ALR2.