Please use this identifier to cite or link to this item: doi:10.22028/D291-30135
Title: Muraymycin Nucleoside Antibiotics: Structure-Activity Relationship for Variations in the Nucleoside Unit
Author(s): Heib, Anna
Niro, Giuliana
Weck, Stefanie C.
Koppermann, Stefan
Ducho, Christian
Language: English
Title: Molecules
Volume: 25
Issue: 1
Publisher/Platform: MDPI
Year of Publication: 2019
Free key words: antibiotics
natural products
nucleoside analogues
structure–activity relationships
DDC notations: 500 Science
600 Technology
610 Medicine and health
Publikation type: Journal Article
Abstract: Muraymycins are a subclass of naturally occurring nucleoside antibiotics with promising antibacterial activity. They inhibit the bacterial enzyme translocase I (MraY), a clinically yet unexploited target mediating an essential intracellular step of bacterial peptidoglycan biosynthesis. Several structurally simplified muraymycin analogues have already been synthesized for structure–activity relationship (SAR) studies. We now report on novel derivatives with unprecedented variations in the nucleoside unit. For the synthesis of these new muraymycin analogues, we employed a bipartite approach facilitating the introduction of different nucleosyl amino acid motifs. This also included thymidine- and 5-fluorouridine-derived nucleoside core structures. Using an in vitro assay for MraY activity, it was found that the introduction of substituents in the 5-position of the pyrimidine nucleobase led to a significant loss of inhibitory activity towards MraY. The loss of nucleobase aromaticity (by reduction of the uracil C5-C6 double bond) resulted in a ca. tenfold decrease in inhibitory potency. In contrast, removal of the 20 -hydroxy group furnished retained activity, thus demonstrating that modifications of the ribose moiety might be well-tolerated. Overall, these new SAR insights will guide the future design of novel muraymycin analogues for their potential development towards antibacterial drug candidates.
DOI of the first publication: 10.3390/molecules25010022
Link to this record: urn:nbn:de:bsz:291--ds-301352
ISSN: 1420-3049
Date of registration: 9-Dec-2020
Description of the related object: Supplementary Materials
Related object:
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Christian Ducho
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Files for this record:
File Description SizeFormat 
molecules-25-00022-v2.pdf3,35 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons