Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE

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

doi:10.3390/antibiotics9090595

Title: Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE

Journal Article · Fri Sep 11 00:00:00 EDT 2020 · Antibiotics

DOI:https://doi.org/10.3390/antibiotics9090595· OSTI ID:1764848

Reidl, Cory T. ^[1]; Heath, Tahirah K. ^[2]; Darwish, Iman ^[2];

^[2]; Moore, Maxwell ^[2]; Gild, Elliot ^[2]; Nocek, Boguslaw P. ^[3]; Starus, Anna ^[2]; Holz, Richard C. ^[4];

^[2]

Loyola Univ., Chicago, IL (United States); Northwestern Univ., Evanston, IL (United States)
Loyola Univ., Chicago, IL (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)
Colorado School of Mines, Golden, CO (United States)

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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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: AC02-06CH11357; HHSN272200700058C; HHSN272201200026C; CHE-1412443

OSTI ID:: 1764848

Journal Information:: Antibiotics, Vol. 9, Issue 9; ISSN 2079-6382

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
DapE
antibiotic
diaminopimelate desuccinylase
enzyme inhibition
indoline
ninhydrin enzyme assay
sulfonamide

Title: Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE

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References (27)

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