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Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE
Cory T Reidl1,2, Tahirah K Heath1, Iman Darwish1
1Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
Abstract:
Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).
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