Discovery of a novel class of small-molecule antibacterial agents against Staphylococcus aureus

Background: With constantly increasing resistance against the known antibiotics, the search for novel antibacterial compounds is a challenge. The number of synthetic antibacterial agents is limited. Materials & methods: We discovered novel small-molecule antibacterial agents that are accessible via a simple two-step procedure. The evaluation against Staphylococcus aureus showed antibacterial effects depending on the substituent positioning at the residues of the molecular scaffold. Additionally, we investigated the potential of the compounds to increase the antibacterial activity of tetracycline. Results: The most effective antibacterial compounds possessed a 3-methoxy function at an aromatic residue. In combination with tetracycline, we found a strong effect for a few compounds in boosting the antibacterial activity, so the first promising lead compounds with dual activities could be identified.

Automated summary

Novel small-molecule antibacterial agents were synthesized via a two-step procedure, showing antibacterial effects on Staphylococcus aureus with activity depending on substituent positioning. Some compounds were found to enhance the antibacterial activity of tetracycline, leading to the identification of promising lead compounds with dual activities.