Discovery of novel <scp>MurB</scp> inhibitors through common feature pharmacophore–based virtual screening and in vitro biological evaluation

Abstract MurB, a key enzyme involved in bacterial cell wall synthesis, has become an important target in antibacterial drug research due to its crucial role in inhibiting peptidoglycan biosynthesis. In this study, a virtual screening workflow based on common‐feature pharmacophore models was established using Discovery Studio software. Molecular docking was subsequently performed with FRED, and 13 potential active compounds were successfully identified through visual inspection and structural clustering. These compounds were then subjected to in vitro biological activity evaluation, from which two active compounds, A1 and A10, were ultimately identified. Furthermore, molecular dynamics simulations were employed to investigate the binding modes between the protein and ligands in greater detail. The physicochemical properties and potential toxicity of A1 and A10 were also predicted and analyzed. In summary, this study successfully identified novel MurB inhibitors through a combination of virtual screening and in vitro biological evaluation, providing valuable support for further research and development of antibacterial agents and demonstrating promising application potential.