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<p>α-Glucosidase has always been one essential target for clinical prevention and treatment of diabetes. To develop effective α-glucosidase inhibitors, twenty-seven thiadiazole based β-carboline derivatives (TC1–TC27) were designed and synthesized by pharmacophore hybridization strategy, and systematically evaluated their inhibitory activity and binding characteristics against α-glucosidase. All synthesized derivatives (TC1–TC27) displayed significant inhibitory activity against α-glucosidase, with TC16 emerging as the most potent compound (IC<sub>50</sub> = 2.62 ± 0.21&#xa0;μM), far surpassing the reference inhibitor acarbose (IC<sub>50</sub> = 210.75 ± 9.52&#xa0;μM). Furthermore, fluorescence spectra and CD spectra results illustrated the binding of TC16 onto α-glucosidase, which caused the enzyme conformation transition to induce activity decrease. Finally, molecular docking elucidated hydrogen bonds and hydrophobic interactions kept the binding of TC16 onto α-glucosidase. In summary, this work provides a class of thiadiazole based β-carboline derivatives as potential α-glucosidase inhibitors.</p>

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Thiadiazole based β-carboline derivatives as potential α-glucosidase inhibitors: design, synthesis, and bioactivity evaluation

  • 期刊论文

  • 发表日期：

    2025年10月5日

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  • Huan Zhou,
  • Yaxin Wen,
  • Shao-Hua Wang,
  • Yan Liu,
  • Baoqiong Li,
  • Xuetao Xu

摘要

α-Glucosidase has always been one essential target for clinical prevention and treatment of diabetes. To develop effective α-glucosidase inhibitors, twenty-seven thiadiazole based β-carboline derivatives (TC1–TC27) were designed and synthesized by pharmacophore hybridization strategy, and systematically evaluated their inhibitory activity and binding characteristics against α-glucosidase. All synthesized derivatives (TC1–TC27) displayed significant inhibitory activity against α-glucosidase, with TC16 emerging as the most potent compound (IC50 = 2.62 ± 0.21 μM), far surpassing the reference inhibitor acarbose (IC50 = 210.75 ± 9.52 μM). Furthermore, fluorescence spectra and CD spectra results illustrated the binding of TC16 onto α-glucosidase, which caused the enzyme conformation transition to induce activity decrease. Finally, molecular docking elucidated hydrogen bonds and hydrophobic interactions kept the binding of TC16 onto α-glucosidase. In summary, this work provides a class of thiadiazole based β-carboline derivatives as potential α-glucosidase inhibitors.