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Activity of singly and doubly modified derivatives of C20-epi-salinomycin against Staphylococcus strains

The Journal of Antibiotics volume 75, pages 445–453 (2022)Cite this article

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Abstract

Natural polyether ionophore salinomycin (Sal) has been widely used in veterinary medicine as an antibiotic effective in the treatment of coccidian protozoa and Gram-positive bacteria. Moreover, chemical modification of the Sal structure has been found to be a promising strategy to generate semisynthetic analogs with biological activity profiles improved relative to those of the native compound. In this context, we synthesized and thoroughly evaluated the antibacterial potential of a library of C1/C20 singly and doubly modified derivatives of C20-epi-salinomycin, that is, analogs of Sal with inversed stereochemistry at the C20 position. Among the synthesized analog structures, the most promising antibacterial active agents were those obtained via regioselective O-acylation of C20-epi-hydroxyl, particularly esters 7, 9, and 11. Such C20 singly modified compounds showed excellent inhibitory activity against planktonic staphylococci, both standard and clinical strains, and revealed potential in preventing the formation of bacterial biofilms. In combination with their non-genotoxic properties, these Sal derivatives represent attractive candidates for further antimicrobial drug development.

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Scheme 1
Scheme 2
Fig. 1

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Acknowledgements

The project was carried out using the infrastructure of the Centre for Preclinical Research and Technology financed by the European Union – European Regional Development Fund within the ‘Innovative Economy’ Operational Program for 2007–2013. DC wishes to acknowledge the scholarship no. POWR. 03.02.00-00-I026/16, co-financed by the European Union through the European Social Fund under the Operational Program Knowledge Education Development. DC also wishes to acknowledge the Polish Science Center (NCN) for the ETIUDA doctoral scholarship (2020/36/T/ST4/00041).

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Authors and Affiliations

  1. Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61–614, Poznań, Poland

    Dominika Czerwonka, Michał Antoszczak & Adam Huczyński

  2. Department of Biochemistry, Medical University of Warsaw, 02–097, Warsaw, Poland

    Małgorzata Podsiad

  3. Laboratory of Pharmaceutical Microbiology, Centre for Preclinical Research, Medical University of Warsaw, 02–097, Warsaw, Poland

    Joanna Stefańska

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  1. Dominika Czerwonka
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Correspondence to Michał Antoszczak.

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Czerwonka, D., Podsiad, M., Stefańska, J. et al. Activity of singly and doubly modified derivatives of C20-epi-salinomycin against Staphylococcus strains. J Antibiot 75, 445–453 (2022). https://doi.org/10.1038/s41429-022-00536-4

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