Parallel solid synthesis of inhibitors of the essential cell division FtsZ enzyme as a new potential class of antibacterials

Article abstract of DOI:10.1016/j.bmc.2006.11.015

As a model system for designing new inhibitors of bacterial cell division, we studied the essential and highly conserved FtsZ GTPase from Pseudomonas aeruginosa. A collection of GTP analogues were prepared using the solid-phase parallel synthesis approach. The synthesized GTP analogues inhibited the GTPase activity of FtsZ with IC₅₀ values between 450 μM and 2.6 mM, and 5 compounds inhibited Staphylococcus aureus growth in a biological assay. The FtsZ spectrophotometric assay developed for screening of synthesized compounds is the first step in identification of antibacterials targeting the bacterial cell division essential proteins.