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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

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Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE.

Reidl Cory T CT Heath Tahirah K TK Darwish Iman I Torrez Rachel M RM Moore Maxwell M Gild Elliot E Nocek Boguslaw P BP Starus Anna A Holz Richard C RC Becker Daniel P DP

Antibiotics (Basel, Switzerland) 20200911 9

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 ...[more]

PMID: 32933028

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