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Issue 28, 2015
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Design, synthesis and biological evaluation of 5′-C-piperidinyl-5′-O-aminoribosyluridines as potential antibacterial agents

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Abstract

The discovery of new antibiotics is critical because the emergence of drug-resistant bacteria has posed a serious public health problem. Caprazamycins, which are nucleoside antibiotics, are a promising lead with a novel mode of action, and we have designed simplified analogues containing a piperidine as a scaffold linking the crucial structural units of caprazamycins. These analogues were step-economically synthesized via a sequential aza-Prins–Ritter reaction. Among the tested compounds, the analogue 7 exhibited good MraY inhibitory activity, antibacterial activity against Gram-positive bacterial strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci, and metabolic stability. The observed cytotoxicity of 7 against HepG2 cells was overcome by modulating the fatty acyl side chain. The knowledge obtained from our structure–activity relationship studies of the caprazamycins will provide further direction toward the design of potent MraY inhibitors.

Graphical abstract: Design, synthesis and biological evaluation of 5′-C-piperidinyl-5′-O-aminoribosyluridines as potential antibacterial agents

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Article information


Submitted
22 May 2015
Accepted
09 Jun 2015
First published
09 Jun 2015

Org. Biomol. Chem., 2015,13, 7720-7735
Article type
Paper

Design, synthesis and biological evaluation of 5′-C-piperidinyl-5′-O-aminoribosyluridines as potential antibacterial agents

T. Nakaya, A. Matsuda and S. Ichikawa, Org. Biomol. Chem., 2015, 13, 7720
DOI: 10.1039/C5OB01037C

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