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

Piotr Przybylski; Krystian Pyta; Dominika Czerwonka; Marcelina M Kubicka; Marzena Gajecka

doi:10.1016/j.bmcl.2015.07.043

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. 2015 Sep 15;25(18):3903-9. doi: 10.1016/j.bmcl.2015.07.043. Epub 2015 Jul 22.

Authors

Piotr Przybylski¹, Krystian Pyta², Dominika Czerwonka², Marcelina M Kubicka³, Marzena Gajecka⁴

Affiliations

¹ Faculty of Chemistry, A. Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland. Electronic address: piotrp@amu.edu.pl.
² Faculty of Chemistry, A. Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland.
³ Department of Genetics and Pharmaceutical Microbiology, University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.
⁴ 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.

PMID: 26254943
DOI: 10.1016/j.bmcl.2015.07.043

Abstract

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.

Keywords: Antibacterial; Bacterial RNA polymerases; Complexes; LogP; Rifamycin antibiotics; Solubility.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Dose-Response Relationship, Drug
Ethers / chemistry*
Ethers / pharmacology
Lithium / chemistry
Lithium / pharmacology
Macrocyclic Compounds / chemistry*
Macrocyclic Compounds / pharmacology
Microbial Sensitivity Tests
Molecular Conformation
Nitrogen / chemistry*
Organometallic Compounds / chemical synthesis
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology*
Rifamycins / chemistry
Rifamycins / pharmacology
Sodium / chemistry
Sodium / pharmacology
Staphylococcus aureus / drug effects*
Staphylococcus epidermidis / drug effects*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Ethers
Macrocyclic Compounds
Organometallic Compounds
Rifamycins
3-formylrifamycin SV
Lithium
Sodium
Nitrogen