‘Unlocking the potential of cefuroxime axetil metal complexes: a multifaceted approach to discovering <i>β</i> -glucosidase inhibitors through MD simulations, POM analyses, and pharmacophore site identification’

Due to the poor bioavailability of Cefuroxime axetil, the current study explored the synthesis of complexes of a Cefuroxime axetil with metal ions thereby increasing their biological activities. This structural modification on the one hand solves the solubility problem and on the other hand may tend to improve the pharmacology, toxicology, and other physio-chemical properties of the drug. Cefuroxime-loaded metal complexes <b>(1-6)</b> of CrBr₃.6H₂O, CoCl₂.6H₂O, CuCl₂, MnCl₂.H₂O, NiCl₂.H₂O, and ZnCl₂ were synthesized in equimolar ratios where the drug acts as a bis-bidentate ligand. These complexes were characterized by using UV-<i>Vis</i>, FT-IR, and TGA. The synthesized metal complexes were subjected to enzyme inhibition assay targeting <i>β</i>-glucosidase. The Cefuroxime-copper (II) complex was found to be 5 times more active as compared to the free ligand, and almost 1.2 times more active compared to the standard drug. The binding energy of a ligand with a metal ion provides insight into the complicated molecular processes involved in the binding of protein-metal complexes through in-silico study. The criteria set forth for the confirmation were binding energy ΔG, and root mean square deviation using MoE software. Molecular docking study reveals the binding energy of ligands with metal ions. MD simulations unveiled a robust binding affinity between the inhibitors and the active site of <i>β</i>-glucosidase, inducing notable structural conformational alterations within the protein. Conclusively, These metal complexes have a greater capacity to block <i>β</i>-glucosidase activity than standard drugs, as evidenced by their binding energy and interaction pattern inside the active pocket, making them a better drug candidate.