New Imidazo[2,1-b]thiazole Linked Hydrazide–Hydrazones as Potent α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and Docking Insights

Inhibition of the α-glucosidase enzyme slows glucose absorption, thereby aiding in the regulation of blood sugar levels. This approach offers a promising way to manage type 2 diabetes with fewer side effects than traditional treatments. Based on this rationale, we designed, synthesised, and characterised a novel series of hydrazide–hydrazone-linked imidazo[2,1-b]thiazole derivatives. Inhibiting the α-glucosidase enzyme slows down glucose absorption, thereby helping to regulate blood sugar levels. This approach offers a promising way to manage type 2 diabetes with fewer side effects than traditional treatments. Based on this, we designed, synthesized, and characterized a new series of hydrazide–hydrazone-linked imidazo[2,1-b]thiazole derivatives. In addition, their efficacy as α-glucosidase inhibitors was evaluated, and several of the synthesized compounds exhibited impressive in vitro α-glucosidase inhibitory activity, with compound 4j (IC₅₀: 0.0284 ± 0.0006 mM) being the most potent among them. To determine the key interactions between compound 4j and the enzyme and to shed light on its mechanism of action, docking studies were conducted. As a result, we found that the derivative containing the 2,6-dichlorophenyl moiety exhibited the highest affinity for the α-glucosidase enzyme and could inhibit it by binding to either the active or allosteric site.