Synthesis, antidiabetic activity and molecular docking study of rhodanine-substitued spirooxindole pyrrolidine derivatives as novel ?-amylase inhibitors

In a sustained search for novel ?-amylase inhibitors the treatment of type 2 diabetes mellitus (T2DM), we report herein synthesis series nineteen rhodanine-fused spiro[pyrrolidine-2,3?-oxindoles]. They were obtained by one-pot three component [3 + 2] cycloaddition stabilized azomethine ylides, generated in situ condensation glycine methyl ester and cyclic ketones 1H-indole-2,3-dione (isatin), with (Z)-5-arylidine-2-thioxothiazolidin-4-ones. The highlight this protocol is efficient high-yield construction structurally diverse spiro[pyrrolidine-2,3?-oxindoles] scaffolds, including four contiguous stereocenters, along excellent regio- diastereoselectivities. stereochemistry all compounds was confirmed NMR corroborated an X-ray diffraction study performed on one derivative. All cycloadducts evaluated vitro their inhibitory activity showed good inhibition IC50 values ranging between 1.49 ± 0.10 3.06 0.17 µM, respect to control drug acarbose (IC50 = 1.56 µM). Structural relationships (SARs) also established synthesized binding interactions most active spiropyrrolidine derivatives modelled means molecular silico docking studies. potent 5 g, k, s l further screened vivo hypoglycemic alloxan-induced diabetic rats, showing reduction blood glucose level. Therefore, these may be considered as promising candidates development new classes antidiabetic drugs.