New ?-carboline derivatives as potential ?-glucosidase inhibitor: Synthesis and biological activity evaluation

alpha-Glucosidase is an important therapeutic target of diabetes mellitus. To find potent alpha-glucosidase in-hibitors, thirty-one $-carboline derivatives containing piperazine moieties (6a-6u, 7a-7j) were synthe-sized and evaluated their alpha-glucosidase inhibitory activity. Most $-carboline derivatives showed poten-tial alpha-glucosidase inhibitory activity, especially, compound 7c presented obvious alpha-glucosidase inhibitory activity (IC50: 8.9 +/- 0.2 mu M), similar to 69 folds stronger than acarbose (IC50: 610.7 +/- 0.1 mu M). Inhibition mecha-nism and kinetics explained compound 7c to be a reversible and mixed-type inhibitor. CD spectra, 3D flu-orescence, and molecular docking were employed to reveal the mechanisms of 7c against alpha-glucosidase. Cell cytotoxicity assay ascertained low cytotoxicity of 7c. (c) 2023 Elsevier B.V. All rights reserved.