The bacterial resistance to antibiotics is becoming an increasing health problem. The main reasons are inappropriate use of antibiotics and the decreasing number of novel antibiotics. For this reason, the development and synthesis of new antibacterial agents is required. Studies have shown that enzymes involved in intracellular levels of peptidoglycan biosynthesis have a great potential for the development of new antibacterial agents.
In our work we synthesized new pyridinostylbene inhibitors of ATP dependent MurC–F ligases, which catalyses the addition of peptides to peptidoglycan precursor. A new series of inhibitors was designed and synthesized, based on the structure of the known inhibitor, which was identified in the screening of the library of protein kinase inhibitors against Mur ligases at the Faculty of Pharmacy. First, we replaced the furan ring with various aromatic fragments and synthesized five new MurC–F inhibitors. Additionally, the tetrazole moiety of the molecule was changed, and two additional MurC–F inhibitors were synthesized.
By replacing the furan fragment, a MurC–F enzyme inhibitor was obtained which had similar activity to the starting compound (compound 4b). Pyridinostylbene derivatives with altered tetrazole moiety 5 and 6 were also proven to be good inhibitors.
Synthesized derivatives provide a good starting point for further synthesis and design of multiple inhibitors of the MurC-F ligases.