Indoline‐6‐Sulfonamide Inhibitors of the Bacterial Enzyme DapE

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

doi:10.3390/antibiotics9090595

Indoline‐6‐Sulfonamide Inhibitors of the Bacterial Enzyme DapE

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

Department of Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

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).

Original language	American English
Journal	Chemistry: Faculty Publications and Other Works
Volume	9
Issue number	9
DOIs	https://doi.org/10.3390/antibiotics9090595
State	Published - Sep 11 2020

Keywords

diaminopimelate desuccinylase
DapE
ninhydrin enzyme assay
indoline
sulfonamide
enzyme inhibition
antibiotic

Disciplines

Biochemistry
Chemistry

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Indoline 6 Sulfonamide Inhibitors of the Bacterial Enzyme DapEFinal published version, 1.98 MBLicense: Unspecified

Cite this

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title = "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).",

keywords = "diaminopimelate desuccinylase, DapE, ninhydrin enzyme assay, indoline, sulfonamide, enzyme inhibition, antibiotic",

author = "Reidl, \{Cory T\} and Heath, \{Tahirah K\} and Iman Darwish and Torrez, \{Rachel M\} and Maxwell Moore and Elliot Gild and Nocek, \{Boguslaw P\} and Anna Starus and Holz, \{Richard C\} and Becker, \{Daniel P\}",

year = "2020",

month = sep,

day = "11",

doi = "10.3390/antibiotics9090595",

language = "American English",

volume = "9",

journal = "Chemistry: Faculty Publications and Other Works",

number = "9",

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TY - JOUR

T1 - Indoline‐6‐Sulfonamide Inhibitors of the Bacterial Enzyme DapE

AU - Reidl, Cory T

AU - Heath, Tahirah K

AU - Darwish, Iman

AU - Torrez, Rachel M

AU - Moore, Maxwell

AU - Gild, Elliot

AU - Nocek, Boguslaw P

AU - Starus, Anna

AU - Holz, Richard C

AU - Becker, Daniel P

PY - 2020/9/11

Y1 - 2020/9/11

N2 - 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).

AB - 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).

KW - diaminopimelate desuccinylase

KW - DapE

KW - ninhydrin enzyme assay

KW - indoline

KW - sulfonamide

KW - enzyme inhibition

KW - antibiotic

UR - https://ecommons.luc.edu/chemistry_facpubs/114

UR - https://ecommons.luc.edu/chemistry_facpubs/121

U2 - 10.3390/antibiotics9090595

DO - 10.3390/antibiotics9090595

M3 - Article

VL - 9

JO - Chemistry: Faculty Publications and Other Works

JF - Chemistry: Faculty Publications and Other Works

IS - 9

ER -

Indoline‐6‐Sulfonamide Inhibitors of the Bacterial Enzyme DapE

Abstract

Keywords

Disciplines

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