Design and Synthesis of Novel Imidazo[2,1-b]thiazole-Based 4- Thiazolidinone Derivatives as Potent α-Glucosidase Inhibitors

<strong>Background and Aims: </strong>Inhibiting the α-glucosidase reduces the rate at which glucose is absorbed, helping to control blood sugar levels. This strategy presents a potential alternative for managing type 2 diabetes, offering a promising approach with fewer adverse effects compared with conventional treatments. Based on this, we synthesised novel imidazo[2,1-b]thiazole-based 4-thiazolidinone derivatives (5a-e) and eval uated them for their α-glucosidase inhibitory activities. <strong>Methods:</strong> Structural confirmation of the synthesised compounds was carried out using various spectro scopic techniques, including IR, ¹H-NMR and ¹³C-NMR spectroscopy, elemental analysis and ESI-MS. The newly synthesised compounds were subjected to <em>in vitro</em> evaluation to assess their inhibitory effects on α-glucosidase activity. <strong>Results: </strong>Spectroscopic analyses confirmed the successful synthesis of the target compounds. Among them, compound <strong>5e </strong>exhibited the most potent α-glucosidase inhibitory effect, with a half-maximal inhibitory concentration (IC₅₀) value of 115.94 ± 0.58 µM, outperforming the standard drug acarbose, which showed an IC₅₀ of 179.25 ± 3.41 µM. <strong>Conclusion: </strong>In summary, a series of novel imidazo[2,1-<em>b</em>]thiazole-based 4-thiazolidinone derivatives (<strong>5a-e</strong>) were successfully synthesised, among which compound <strong>5e </strong>emerged as the most potent α-glucosidase inhibitor, surpassing the activity of the reference drug acarbose. These findings position compound <strong>5e</strong> as a promising lead candidate for developing new α-glucosidase inhibitory agents. To fully assess the therapeutic value of this scaffold, further<em> in vitro </em>investigations on structurally related analogs, followed by comprehensive <em>in vivo</em> assessments, are warranted.