Carbazole-Based Ester Derivatives as Potential α-Glucosidase Inhibitors; Synthesis, Biological Evaluation, and Molecular Docking Studies

In this study, a new range of carbazole linked mono- and bis-ester derivatives were successfully synthesized and evaluated for their in vitro anti-diabetic activity through α-amylase and α-glucosidase inhibition. The synthetic approach for the preparation of mono-esters 5a–j and bis-esters 7a–j was achieved by the reaction of carbazole-3-methanol 4 and carbazole-3,6-dimethanol 6 with a variety of acyl chlorides. The targeted compounds displayed generally weak α-amylase inhibition but significant and selective inhibition against α-glucosidase. Among them, 7a, 7g, and 7j exhibited dual inhibitory activity, while 7f was selective for α-glucosidase, and 7d and 5g for α-amylase. Notably, 7g was the most potent compound (IC50 = 22.79 µM), surpassing Acarbose. In addition, molecular docking studies of the synthesized compounds were carried out to investigate their interactions with the α-glucosidase enzyme. Overall, targeted carbazole-based ester derivatives show promising results as selective anti-diabetic agents.