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).

SUBMITTER: Reidl CT 

PROVIDER: S-EPMC7560015 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature