Synthesis, spectroscopy and biological investigation via DFT, ADMET and molecular docking of Thiadiazole/Oxadiazole based bis-Schiff bases: A potential towards diabetes and microbes

• Synthesis of Thiadiazole/Oxadiazole based bis- Schiff base derivatives. • Biologically investigation for their anti-diabetic potential. • Structural confirmation of the synthesized compounds via spectroscopic analysis. • Conducted in silico molecular docking study to gain insight into binding interactions with target enzymes. • Stability of the potent compounds was analyzed via Density Functional Theory (DFT). • Study of pharmacokinetic properties through ADME analysis for drug likeness attributes. A novel series of varied substituted thiadiazole/oxadiazole based bis-Schiff base derivatives (1–10) was synthesized and characterized using NMR ( 13 CNMR and 1 HNMR) and HREI-mass spectrometry. To determine their anti-diabetic potential, these analogues were examined against α-amylase and α-glucosidase. These compounds demonstrated varied inhibitory range between IC 50 = 1.10 ± 0.50 to 21.40 ± 0.20 µM (α-amylase) and 2.50 ± 0.05 to 21.40 ± 0.10 µM (α-glucosidase), when contrasted with Acarbose, a well-known marketed drug (IC 50 = 3.16 ± 0.22 & 4.8 ± 0.21 µM for α-amylase and α-glucosidase respectively). Analog- 9 having tri-fluoromethyl group at para position of benzene ring emerged as lead candidate among these synthesized compounds. The effective activity of compound- 9 may be due to involvement of fluoro atoms interacting via hydrogen-bonding with the selected sites of diabetic enzymes, α-amylase and α-glucosidase. Furthermore, for exploration of binding interactions of potent drugs and reactivity of potent analogues, molecular docking as well as DFT was performed. For investigation of drug likeness and toxicity, ADME analysis was also conducted.