N-Benzyl-3-sulfonamidopyrrolidines as novel inhibitors of cell division in E. coli

A new small molecule inhibitor of bacterial cell division has been discovered using a high-throughput screen in Escherichia coli. Although the lead screening hit (534F6) exhibited modest inhibition of the GTPase activity of FtsZ (20 ± 5% at 100 μM of compound), a primary target for bacterial cell division inhibitors, several analogs caused potent bacterial growth inhibition with negligible antagonism of FtsZ GTPase activity. A library of analogs has been prepared and several alkyne-tagged photoaffinity probes have been synthesized for use in experiments to elucidate the primary target of this compound.

Graphical abstractThe discovery and preliminary development of a new class of compounds that target bacterial cell division is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide