Novel oxazole based oxadiazole conjugates: Synthesis, DFT study and in silico confirmation as potent anti-diabetic agents.

In an approach to combat Diabetes mellitus (a severe metabolic disorder), novel oxazole derived oxadiazole derivatives (1-16) were synthesized having improved biological profile and minimal side effects. These compounds were screened for their biological potential against alpha-amylase and alpha-glucosidase in comparison to standard drug acarbose (4.50 ± 0.20 and 5.10 ± 0.20 µM). All these derivatives exhibited moderate to excellent anti-diabetic activity and have inhibitory concentration range of (15.20 ± 0.20-2.10 ± 0.10 µM) for alpha-amylase and (15.70 ± 0.50-2.40 ± 0.20 µM) for alpha-glucosidase. Analog 8 (2.10 ± 0.10, 2.40 ± 0.20 µM) emerged as lead compound with strong anti-diabetic profile in comparison to all remaining analogues and acarbose. Moreover, these biological findings were correlated with computational approaches. Molecular docking revealed the feasible interactions between ligand and targeted enzymes suggesting the therapeutic potential of lead compounds. DFT calculation confirmed the electronic structure along with stability and reactivity of potent molecules, confirming the promising inhibition profile. The ADMET analysis provided insights into the predicted pharmacokinetic properties and toxicity profiles of these compounds, which play a critical role in evaluating their overall drug-like characteristics. The preclinical data from in-vitro and in-silico studies suggest that these novel compounds possess significant potential as safe and effective anti-diabetic therapies, meriting consideration for future clinical trials and potential therapeutic use.