Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 18.104.22.168) 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).
Reidl, Cory T.; Heath, Tahirah K.; Darwish, Iman; Torrez, Rachel M.; Moore, Maxwell; Gild, Elliot; Nocek, Boguslaw P.; Starus, Anna; Holz, Richard C.; and Becker, Daniel P. Ph.D.. Indoline-6-Sulfonamide Inhibitors of the Bacterial Enzyme DapE. Antibiotics, 9, 9: , 2020. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.3390/antibiotics9090595
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
© The Author, 2020.