Molecules (Jul 2023)

Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

  • Mengyue Li,
  • Lin Li,
  • Li Lu,
  • Xuetao Xu,
  • Jinhui Hu,
  • Jin-Bao Peng

DOI
https://doi.org/10.3390/molecules28135282
Journal volume & issue
Vol. 28, no. 13
p. 5282

Abstract

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To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1–20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.

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