Synthesis and Multi‐Target Inhibition of <i>Bis</i> ‐Schiff Bases of Barbituric Acid: in Vitro α‐glucosidase, α‐amylase Inhibitory Activities With Docking and DFT Studies

Abstract The current research is based on the synthesis of some novel bis ‐Schiff bases bearing barbituric acid moiety followed by characterization through modern spectroscopic techniques and their in vitro inhibitory effects against the enzymes α‐glucosidase and α‐amylase were subsequently investigated. In the series, four compounds 8 (IC 50 = 5.62 ± 0.18 and 3.12 ± 0.13 µM), 10 (IC 50 = 7.13 ± 1.03 and 8.19 ± 1.11 µM), 9 (IC 50 = 12.81 ± 1.92 and 12.11 ± 1.32 µM), and 11 (IC 50 = 15.07 ± 0.38 and 16.01 ± 0.28 µM) attributed notable dual inhibition against α‐glucosidase and α‐amylase enzymes better than the standard acarbose drug (IC 50 = 16.16 ± 0.15 and 16.65 ± 0.17 µM). The molecular docking study was performed to explored the binding affinities and key interactions of synthesized compounds with targeted proteins (α‐amylase and α‐glucosidase). Furthermore, the stability of all the compounds were verified by density functional theory (DFT) method at B3LYP/6–311++G(d,p). For the account of intramolecular interaction, DFT‐D3 and reduced density gradient (RDG) methods were utilized. In addition, utilising the CAM‐B3LYP functional with 6–311++G(d,p), the TD‐DFT approach was used to examine different reactivity circumstances.