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Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE


Reidl, Cory T.; Heath, Tahirah; Darwish, Iman; Torrez, Rachel M. ; Moore, Maxwell; Gild, Elliot ; Nocek, Boguslaw; Starus, Anna; Holz, Richard C. ; Becker, Daniel


Inhibitors of the bacterial enzyme dapE-encodedN-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 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).