Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE

oleh: 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

Format: Article
Diterbitkan: MDPI AG 2020-09-01

Deskripsi

Inhibitors of the bacterial enzyme dapE-encoded <i>N</i>-succinyl-<span style="font-variant: small-caps;">l,l</span>-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).