Show simple item record

dc.contributor.authorGalster, Magdalena
dc.contributor.authorLoeppenberg, Marius
dc.contributor.authorGalla, Fabian
dc.contributor.authorBörgel, Frederik
dc.contributor.authorAgoglitta, Oriana
dc.contributor.authorKirchmair, Johannes
dc.contributor.authorHoll, Ralph
dc.PublishedGalster, Loeppenberg, Galla, Börgel, Agoglitta, Kirchmair J, Holl. Phenylethylene glycol-derived LpxC inhibitors with diverse Zn2+-binding groups. Tetrahedron. 2019;75(4):486-509eng
dc.descriptionUnder embargo until: 10.12.2020
dc.description.abstractThe Zn2+-dependent bacterial deacetylase LpxC is a promising target for the development of novel antibiotics. Most of the known LpxC inhibitors carry a hydroxamate moiety as Zn2+-binding group. However, hydroxamic acids generally exhibit poor pharmacokinetic properties. (S)-N-Hydroxy-2-{2-hydroxy-1-[4-(phenylethynyl)phenyl]ethoxy}acetamide (3) is a known phenylethylene glycol derivative potently inhibiting LpxC with a Ki of 66 nM. In vitro experiments have confirmed in silico predictions that the hydroxamate moiety of 3 is indeed metabolically labile. In this study, several strategies were explored to replace the hydroxamate moiety by other Zn2+-binding groups while maintaining target activity. In total, 15 phenylethylene glycol derivatives with diverse Zn2+-binding groups like carboxylate, hydrazide, carboxamide, sulfonamide, vicinal diol, thiol, thioester, and hydroxypyridinone moieties were prepared in divergent syntheses. However, their biological evaluation revealed that the replacement of the hydroxamate moiety of 3 by any of the investigated Zn2+-binding groups is detrimental for LpxC inhibitory and antibacterial activity.en_US
dc.rightsAttribution CC BY-NC-NDeng
dc.titlePhenylethylene glycol-derived LpxC inhibitors with diverse Zn2+-binding groupsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 Elsevieren_US
dc.relation.projectBergens forskningsstiftelse: BFS2017TMT01

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution CC BY-NC-ND
Except where otherwise noted, this item's license is described as Attribution CC BY-NC-ND