Thiazole–Thiadiazole Compounds for Enzymatic Modulation and Therapeutic Targeting in Diabetes Mellitus

One of the most significant problems facing the scientific community in the 21st century is diabetes mellitus. There is an urgent need to create new powerful compounds that can fight this terrible disease because the number of instances of diabetes and drug-resistant diabetes is rising. We have synthesized a novel series of thiazole-derived thiadiazole-based Schiff base derivatives (1-10) in an effort to identify potential antidiabetic agents. The structures of these compounds were elucidated using a variety of analytical techniques, including ¹H NMR, ¹³C NMR, and HREI-MS. The compounds inhibitory potential against diabetes mellitus was contrasted with that of acarbose, the reference drug. When compared to the reference medication acarbose with IC₅₀ = 7.50 ± 0.10 and 7.80 ± 0.30 µM, analog 8 (IC₅₀ = 4.20 ± 0.10 and 4.80 ± 0.60 µM), analog 5 (IC₅₀ = 5.10 ± 0.30 and 5.60±0.30 µM), and analog 9 (IC₅₀ = 6.20 ± 0.10 and 6.90 ± 0.10 µM) appeared as the most promising inhibitor in this regard. These compounds pharmacological profiles were further investigated by employing molecular docking studies to assess the bonding interactions between ligands and enzymes, whereas dynamic simulations were used to analyze the structural variations and conformational changes of the protein complex. Potent scaffold nontoxic nature was demonstrated by ADMET analysis, which supports their usage as a treatment in the future. Furthermore, DFT analyses provided the charge distribution of the compounds that drive chemical reactivity and enzyme interactions.