Novel Modified Piperacillin Inhibitors of Penicillin-Binding Protein 3 (PBP3) and Their Intermolecular Interactions

<b>Background and Objective:</b> Despite the rise of antibiotic resistance, penicillin and the broader group of β-lactams have continued to be the most crucial class of antibiotics. Penicillin-Binding Protein 3 (PBP3) in <i>Pseudomonas aeruginosa</i> is the specific molecule that β-lactam-based medicines target. The objective is to design and study several piperacillin derivatives to create novel antibacterial agents. <b>Materials and Methods:</b> Piperacillin derivatives were drawn using chem sketch and prepared using AutoDock 4.2.6 Tools. Molecular docking simulations were conducted on novel piperacillin derivatives and piperacillin (Control) against the 6r3x.PDB protein. The AutoDock log files were analyzed to determine the lowest energy of binding (LEB) values for each ligand. Consequently, the conformer with the most favorable binding energy may be identified. <b>Results:</b> All of the proposed piperacillin derivatives displayed improved binding energies when compared to the reference chemical piperacillin. This suggests the potential for stronger interactions between derivatives and proteins, resulting in an enhanced likelihood of biological effects. Compounds b, e and j, when used alongside piperacillin, showed similar binding sites inside the active site and have the potential for additional characterization. <b>Conclusion:</b> Compounds b, e and j are highly likely to exhibit inhibitory activity, indicating that they should be synthesized and tested for biological activity.