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

Abstract

Background and Aims: 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. Methods: 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 in vitro evaluation to assess their inhibitory effects on α-glucosidase activity. Results: Spectroscopic analyses confirmed the successful synthesis of the target compounds. Among them, compound 5e 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. Conclusion: In summary, a series of novel imidazo[2,1-b]thiazole-based 4-thiazolidinone derivatives (5a-e) were successfully synthesised, among which compound 5e emerged as the most potent α-glucosidase inhibitor, surpassing the activity of the reference drug acarbose. These findings position compound 5e as a promising lead candidate for developing new α-glucosidase inhibitory agents. To fully assess the therapeutic value of this scaffold, further in vitro investigations on structurally related analogs, followed by comprehensive in vivo assessments, are warranted.

Keywords

• Synthesis
• Imidazothiazole
• 4-Thiazolidinone
• α-Glucosidase Inhibitory Activity

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