Bromophenol derivatives were evaluated for their inhibitory effects on three key enzymes associated with diabetes: aldose reductase (AR), α-glycosidase, and α-amylase. In vitro enzyme inhibition assays revealed that Compound 6 exhibited the strongest α-glycosidase inhibition (IC50 = 11.948 nM), while Compound 5 showed the highest potency against AR (IC50 = 1.386 µM) and α-amylase (IC50 = 5.588 nM). Selected compounds (5, 6, 7, and 10) displayed low cytotoxicity against normal human fibroblast cells, indicating favorable safety profiles. Complementary induced-fit molecular docking analyses supported the experimental results, highlighting specific interactions between the compounds and the enzyme active sites. These findings demonstrate that bromophenol derivatives possess significant enzyme-inhibitory potential and may serve as promising multifunctional agents for diabetes management. Induced-fit docking studies revealed that Compounds 6, 10, 5, and 7 exhibited the most favorable binding energies across the tested enzymes, consistent with their high inhibitory potential. Compounds 6 and 10 showed strong α-glucosidase binding through key interactions such as π-π stacking with TRP539/PHE575 and TRP406, as well as extensive hydrogen and halogen bonding with catalytic residues including TYR299, ASP203, ASP327, and ARG526. Similarly, Compounds 5 and 7 formed stable docking poses within α-amylase and aldose reductase via multiple hydrogen bonds, halogen contacts, and π-π stacking with crucial residues like ASP197, GLH233, ASN160, TRP20, and TRP219, highlighting their strong affinity and target-specific interactions.
Serpil Gerni (2026) studied this question.