“On water” synthesis of dibenzo-[1,4]-diazepin-1-ones using l-proline as an organocatalyst and under catalyst-free conditions, and their evaluation as α-glucosidase inhibitors

Abstract

Functionalized dibenzo-[1,4]-diazepin-1-ones were synthesized using the “on-water” concept in the presence of L-proline (organocatalyst; 20 mol%) and under catalyst free conditions (sealed tube) in an aqueous medium. The resulting molecules were tested (in vitro) for α-glucosidase (isolated from Saccharomyces cerevisiae) enzyme inhibition using acarbose as a standard drug (IC₅₀ 32.47 ± 1.64). The enzyme inhibition kinetic analysis of selected molecules showed the competitive mode of inhibition (best result; IC₅₀ 39.31 ± 1.68) against α-glucosidase. Molecular docking studies of these compounds with the MAL12 homology model showed HIS279A as a major interacting residue in the binding site of the protein which is a similar binding mode consistent with the binding of acarbose.