Synthesis and biological evaluation of new dihydroindolizino[8,7-b]indole derivatives as novel α-glucosidase inhibitors.

• A new series of dihydroindolizino[8,7- b ]indole derivatives 4a–r was synthesized as α -glucosidase inhibitors. • All synthesized compounds showed anti- α -glucosidase activity superior to standard drug (acarbose). • Compound 4o is the most active compound and a competitive inhibitor for α -glucosidase. • Compound 4o is around 7-fold more potent than acarbose. • Docking studies of the most active compounds 4o and 4 h were also performed. Eighteen dihydroindolizino[8,7- b ]indole derivatives 4a–r were designed, synthesized and evaluated as new α -glucosidase inhibitors. These derivatives were synthesized by an efficient one-pot two-step reaction under mild condition. All the synthesized compounds were found to be more active than the standard drug acarbose (IC 50 = 750.0 ± 1.5 µM) with IC 50 values in the range of 107.2 ± 1.0–275.4 ± 1.5 µM. Among the synthesized compounds, diethyl derivative 4o and dimethyl derivative 4 h exhibited the highest anti-α-glucosidase activities (IC 50 = 107.2 ± 1.0 and 118.0 ± 0.7 µM, respectively). Kinetic analysis of the compound 4o revealed that this compound is a competitive inhibitor for α -glucosidase with K i value of 113 µM. Furthermore, the docking study on the compounds 4o and 4 h revealed that these compounds interacted with the important residues in the active site of the homology model of α -glucosidase. [ABSTRACT FROM AUTHOR]