Novel hybrids of thiazolidinedione-1,3,4-oxadiazole derivatives: synthesis, molecular docking, MD simulations, ADMET study, , and anti-diabetic assessment.

As compared to standard medicinal compounds, hybrid molecules that contain multiple biologically active functional groups have greater affinity and efficiency. Hence based on this concept, we predicted that a combination of thiazolidinediones and 1,3,4-oxadiazoles may enhance α-amylase and α-glucosidase inhibition activity. A series of novel 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)thiazolidine-2,5-dione derivatives (5a-5j) were synthesized and characterized using different spectroscopic techniques , FTIR, H-NMR, C-NMR and MS. To evaluate , molecular docking, MMGBSA, and MD simulations were carried out which were further evaluated inhibition of α-amylase and α-glycosidase enzyme inhibition assays. In addition, the study was performed on a genetic model of to assess the antihyperglycemic effects. The compounds (5a-5j) demonstrated α-amylase and α-glucosidase inhibitory activity in the range of IC values 18.42 ± 0.21-55.43 ± 0.66 μM and 17.21 ± 0.22-51.28 ± 0.88 μM respectively when compared to standard acarbose. Based on the studies, compounds 5a, 5b, and 5j were found to be potent against both enzymes. studies have shown that compounds 5a, 5b, and 5j lower glucose levels in Drosophila. These compounds could be further developed in the future to produce a new class of antidiabetic agents.