Design, synthesis and docking study of novel tetracyclic oxindole derivatives as α-glucosidase inhibitors

A series of novel tetracyclic oxindole derivatives were synthesized via tandem Suzuki coupling–Michael addition reaction catalyzed by palladium. Twenty derivatives were designed and synthesized in 6–8 steps in 8–20% overall yields. Their structures were confirmed by 1H, 13C NMR and LC/MS. These compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 7c, 7d, 7e, 7g, 7h, and 7i exhibited IC50 values of 32.3, 12.1, 15.7, 29.0, 16.0, and 4.8 μM, respectively, with potency all higher than that of the control standard acarbose (IC50 = 115.8 μM). Molecular docking studies revealed the existence of potential hydrogen bonding and hydrophobic interaction between the enzyme and the active compound 7i.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide