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N-Terminal guanidine derivatives of teicoplanin antibiotics strongly active against glycopeptide resistant Enterococcus faecium

The Journal of Antibiotics volume 73, pages 603–614 (2020)Cite this article

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Abstract

Antibiotic resistance is one of the major challenges in healthcare of our time. To meet this challenge, we designed and prepared guanidine and lipophilic guanidine derivatives of the glycopeptide antibiotic teicoplanin to armed them with activity against the most threatening nosocomial bacteria, multiresistant enterococci. From teicoplanin and its pseudoaglycone, a series of N-terminal guanidine derivatives have been prepared with free and amide C-terminal parts. Six aliphatic and aromatic lipophilic carbodiimides were prepared and used for the synthesis of lipophilic guanidine teicoplanin conjugates. All new N-terminal guanidine antibiotics showed high activity against a standard panel of Gram-positive bacteria. Four selected derivatives displayed excellent antibacterial activity against a series of nosocomial VanA Enterococcus faecium strains.

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Acknowledgements

This work was supported by the European Regional Development Fund under the projects GINOP-2.3.2-15-2016-00044 and GINOP-2.3.3-15-2016-00004 and by the European Social Fund under the project EFOP-3.6.3-VEKOP-16-2017-00009. This research was also funded by the National Research, Development and Innovation Office of Hungary (K119509).

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, Egyetem tér 1, H-4032, Hungary

    Zsolt Szűcs, Ilona Bereczki, Erzsébet Rőth, Anikó Borbás & Pál Herczegh

  2. Doctoral School of Pharmaceutical Sciences, University of Debrecen, Debrecen, Hungary

    Zsolt Szűcs

  3. Department of Medical Microbiology, Semmelweis University, Budapest, Nagyvárad tér 4, H-1089, Hungary

    Márton Milánkovits & Eszter Ostorházi

  4. Department of Organic Chemistry, University of Debrecen, Debrecen, Egyetem tér 1, H-4032, Hungary

    Gyula Batta

  5. Department of Applied Chemistry, University of Debrecen, Debrecen, Egyetem tér 1, H-4032, Hungary

    Lajos Nagy

  6. Department of Medical Microbiology, University of Debrecen, Debrecen, Egyetem tér 1, H-4032, Hungary

    Zsuzsanna Dombrádi

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  1. Zsolt Szűcs
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Correspondence to Pál Herczegh.

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Szűcs, Z., Bereczki, I., Rőth, E. et al. N-Terminal guanidine derivatives of teicoplanin antibiotics strongly active against glycopeptide resistant Enterococcus faecium. J Antibiot 73, 603–614 (2020). https://doi.org/10.1038/s41429-020-0313-6

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