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

Abstract 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 1 H, 13 C NMR and LC/MS. These compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 7c , 7d , 7e , 7g , 7h , and 7i exhibited IC 50 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 (IC 50  = 115.8 μM). Molecular docking studies revealed the existence of potential hydrogen bonding and hydrophobic interaction between the enzyme and the active compound 7i .