Novel Imidazo[2,1‐ b ]thiazole Based 4‐Thiazolidinones: Molecular Dynamics Guided Design, Synthesis, and α‐Glucosidase Inhibitory Evaluation

Abstract Inhibition of α‐glucosidase offers a promising strategy to reduce the enzymatic breakdown of complex carbohydrates into glucose, thereby moderating postprandial blood sugar levels and potentially offering a safer approach for managing type 2 diabetes compared to conventional therapies. In this study, we designed, synthesized, and thoroughly characterized a novel series of imidazo[2,1‐ b ]thiazole based 4‐thiazolidinones. These compounds were evaluated for their α‐glucosidase inhibitory potential, and several exhibited exceptional activity, with IC 50 values ranging from 0.0625 ± 0.0019 mM for compound 6g to 0.1412 ± 0.0009 mM for compound 6e , surpassing the potency of the standard inhibitor acarbose (IC 50 : 0.1793 ± 0.0034 mM). Molecular docking studies were carried out to explore the key interactions at the enzyme's active site, providing insight into their mechanism of action. Additionally, molecular dynamics simulations were performed to assess the stability and dynamic behavior of the most potent compounds within the enzyme's binding pocket. Collectively, these findings underline the potential of imidazo[2,1‐ b ]thiazole‐based 4‐thiazolidinone derivatives as a promising new class of α‐glucosidase inhibitors.