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 100microM 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.
Mukherjee
Shubhasish
S
Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
Robinson
Carolyn A
CA
Howe
Andrew G
AG
Mazor
Tali
T
Wood
Peter A
PA
Urgaonkar
Sameer
S
Hebert
Alan M
AM
Raychaudhuri
Debabrata
D
Shaw
Jared T
JT
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006131:Growth Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D006131:Growth Inhibitors; D011759:Pyrrolidines; D013449:Sulfonamides