Indoline‐6‐sulfonamide inhibitors of the bacterial enzyme dape

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).