Integrated Experimental and Computational Investigation of 7‐Bromoochromone Thiosemicarbazones as α‐Glucosidase Inhibitors

ABSTRACT Diabetes mellitus (DM) is a metabolic condition commonly marked by increased blood glucose levels and effectively managed with α‐glucosidase inhibitors. In this study, a novel series of 7‐bromochromone‐based thiosemicarbazones 4(a‐r) was synthesized and assessed for their α‐glucosidase inhibition. All the compounds demonstrated excellent inhibitory potential with IC 50 values in the range of 97.87 ± 0.01 μM—353.34 ± 0.06 μM, vastly outperforming the standard inhibitor acarbose (IC 50 = 871.40 ± 1.24 μM). Compound 4h , bearing a 2,3‐dichlorophenyl substituent, showed the highest potency (97.87 ± 0.01 μM). Molecular docking and molecular dynamics (MD) simulations were conducted to investigate the binding interactions of these compounds within the α‐glucosidase active site. Among the synthesized compounds, 4h demonstrated the most favorable docking configuration and stable binding interactions, suggesting its potential as a lead candidate in the development of novel antidiabetic agents.