The
bacterial cell division protein FtsZ is one of many potential
targets for the development of novel antibiotics. Recently, zantrin
Z3 was shown to be a cross-species inhibitor of FtsZ; however, its
specific interactions with the protein are still unknown. Herein we
report the synthesis of analogues that contain a more tractable core
structure and an analogue with single-digit micromolar inhibition
of FtsZ’s GTPase activity, which represents the most potent
inhibitor of <i>Escherichia coli</i> FtsZ reported to date.
In addition, the zantrin Z3 core has been converted to two potential
photo-cross-linking reagents for proteomic studies that could shed
light on the molecular interactions between FtsZ and molecules related
to zantrin Z3