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

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 IC50 values in the range of 97.87 ± 0.01 μM-353.34 ± 0.06 μM, vastly outperforming the standard inhibitor acarbose (IC50 = 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.