Deciphering enzyme inhibition of thiazole assemblies for diabetes management via molecular docking, dynamic simulation, DFT and kinetic study: A computational therapeutic strategy.
PMID 42000651 | DOI 10.1016/j.compbiolchem.2026.109068 · Computational biology and chemistry · 2026
Diabetes mellitus is a chronic metabolic disorder characterized by impaired insulin secretion and/or insulin resistance, leading to persistent hyperglycemia. In the present study, a series of novel fused imidazole-thiazole-derived thiazole compounds were designed, synthesized, and biologically evaluated for their potential in managing diabetic complications. In vitro enzymatic assays revealed that the synthesized compounds exhibited potent inhibitory activity against key carbohydrate-hydrolyzing enzymes, namely α-glucosidase and α-amylase, which are directly involved in postprandial hyperglycemia. Among the tested compounds, the most active analogue 2 demonstrated superior inhibitory potential with IC₅₀ values of 4.60 ± 0.30 µM (α-glucosidase) and 5.10 ± 0.20 µM (α-amylase), outperforming the standard drug acarbose (IC₅₀ = 7.40 ± 0.20 µM and 8.10 ± 0.10 µM, respectively). The enhanced activity was attributed to the presence of a para-substituted trifluoromethyl (-CF₃) group, which favorably modulates the electronic properties and strengthens enzyme binding interactions. To further validate the experimental findings, molecular docking studies were conducted, which confirmed strong binding affinities of the active compounds within the enzyme active sites through key hydrogen bonding and hydrophobic interactions. Additionally, ADMET analysis suggested favorable pharmacokinetic properties and a promising safety profile of the lead compounds. Overall, the combined in vitro and in silico results indicate that these newly synthesized imidazole-thiazole derivatives represent promising candidates for the development of effective therapeutic agents aimed at the prevention and management of diabetes and its associated complications.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| phenotype | diabetes mellitus | “Deciphering enzyme inhibition of thiazole assemblies for diabetes management via molecular docking, dynamic simulation, DFT and kinetic study: A computational therapeutic strategy.” | 0.93 | phenotype_alias_lexicon_v2 |