Abstract
Muraymycins are a subclass of antimicrobially active uridine-derived natural products. Biological data on several muraymycin analogues have been reported, including some inhibitory in vitro activities toward their target protein, the bacterial membrane enzyme MraY. However, a structure–activity relationship (SAR) study on naturally occurring muraymycins based on such in vitro data has been missing so far. In this work, we report a detailed SAR investigation on representatives of the four muraymycin subgroups A–D using a fluorescence-based in vitro MraY assay. For some muraymycins, inhibition of MraY with IC 50 values in the low-picomolar range was observed. These inhibitory potencies were compared with antibacterial activities and were correlated to modelling data derived from a previously reported X-ray crystal structure of MraY in complex with a muraymycin inhibitor. Overall, these results will pave the way for the development of muraymycin analogues with optimized properties as antibacterial drug candidates.
Original language | English |
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Pages (from-to) | 779-784 |
Number of pages | 6 |
Journal | ChemMedChem |
Volume | 13 |
Issue number | 8 |
DOIs | |
State | Published - Apr 23 2018 |
Bibliographical note
Publisher Copyright:© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords
- activity assays
- antibiotics
- natural products
- nucleosides
- structure–activity relationships
ASJC Scopus subject areas
- Drug Discovery
- General Pharmacology, Toxicology and Pharmaceutics
- Molecular Medicine
- Biochemistry
- Pharmacology
- Organic Chemistry