title: N-Benzyl-3-sulfonamidopyrrolidines as novel inhibitors of cell division in E. coli.
abstract: 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.
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Shubhasish
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Robinson
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Howe
authors.forename: Tali
authors.initials: T
authors.lastname: Mazor
authors.forename: Peter A
authors.initials: PA
authors.lastname: Wood
authors.forename: Sameer
authors.initials: S
authors.lastname: Urgaonkar
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hebert
authors.forename: Debabrata
authors.initials: D
authors.lastname: Raychaudhuri
authors.forename: Jared T
authors.initials: JT
authors.lastname: Shaw
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D006131:Growth Inhibitors; D011759:Pyrrolidines; D013449:Sulfonamides