The effect of complexation of 3-formylrifamycin SV macrocyclic ether derivatives with metal cations and small nitrogen-containing organic molecules on antibacterial activity against S. aureus and S. epidermidis.

Bioorg Med Chem Lett

Department of Genetics and Pharmaceutical Microbiology, University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland; Institute of Human Genetics, Polish Academy of Science, Strzeszynska 32, 60-479 Poznan, Poland.

Published: September 2015

Spectroscopic studies of ether rifamycins (1-9) have shown that all these compounds tend to be zwitterions with different localizations of intramolecularly transferred proton, which influences their solubility and logP values. According to ESI MS studies, rifamycins 3 and 4 form complexes with Li(+) or Na(+), while the other ones (7-9) coordinate small organic molecules, which can be further replaced by Na(+) cation. Biological assays revealed that the use of 7-9 in the form of complexes with small organic molecules improves their antibacterial potency as a result of changed: logP, solubility and binding mode with bacterial RNA polymerases.

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http://dx.doi.org/10.1016/j.bmcl.2015.07.043DOI Listing

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