Next Article in Journal
l-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway
Next Article in Special Issue
Biosynthetic and Synthetic Strategies for Assembling Capuramycin-Type Antituberculosis Antibiotics
Previous Article in Journal
A Null B-Ring Improves the Antioxidant Levels of Flavonol: A Comparative Study between Galangin and 3,5,7-Trihydroxychromone
Previous Article in Special Issue
Novel 5′-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents
Open AccessArticle

Aminoribosylated Analogues of Muraymycin Nucleoside Antibiotics

Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123 Saarbrücken, Germany
Author to whom correspondence should be addressed.
Molecules 2018, 23(12), 3085;
Received: 10 November 2018 / Revised: 21 November 2018 / Accepted: 22 November 2018 / Published: 26 November 2018
(This article belongs to the Special Issue Bioactive Nucleosides and Nucleotides)
Nucleoside antibiotics are uridine-derived natural products that inhibit the bacterial membrane protein MraY. MraY is a key enzyme in the membrane-associated intracellular stages of peptidoglycan biosynthesis and therefore considered to be a promising, yet unexploited target for novel antibacterial agents. Muraymycins are one subclass of such naturally occurring MraY inhibitors. As part of structure-activity relationship (SAR) studies on muraymycins and their analogues, we now report on novel derivatives with different attachment of one characteristic structural motif, i.e., the aminoribose moiety normally linked to the muraymycin glycyluridine core unit. Based on considerations derived from an X-ray co-crystal structure, we designed and synthesised muraymycin analogues having the aminoribose attached (via a linker) to either the glycyluridine amino group or to the uracil nucleobase. Reference compounds bearing the non-aminoribosylated linker units were also prepared. It was found that the novel aminoribosylated analogues were inactive as MraY inhibitors in vitro, but that the glycyluridine-modified reference compound retained most of the inhibitory potency relative to the unmodified parent muraymycin analogue. These results point to 6′-N-alkylated muraymycin analogues as a potential novel variation of the muraymycin scaffold for future SAR optimisation. View Full-Text
Keywords: antibiotics; natural products; nucleoside analogues; structure-activity relationships antibiotics; natural products; nucleoside analogues; structure-activity relationships
Show Figures

Graphical abstract

MDPI and ACS Style

Wiegmann, D.; Koppermann, S.; Ducho, C. Aminoribosylated Analogues of Muraymycin Nucleoside Antibiotics. Molecules 2018, 23, 3085.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop