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


Journal

The Journal of antibiotics
ISSN: 1881-1469
Titre abrégé: J Antibiot (Tokyo)
Pays: England
ID NLM: 0151115

Informations de publication

Date de publication:
09 2020
Historique:
received: 24 02 2020
accepted: 15 04 2020
revised: 26 03 2020
pubmed: 16 5 2020
medline: 29 12 2020
entrez: 16 5 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32409678
doi: 10.1038/s41429-020-0313-6
pii: 10.1038/s41429-020-0313-6
doi:

Substances chimiques

Anti-Bacterial Agents 0
Glycopeptides 0
Guanidines 0
Teicoplanin 61036-62-2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

603-614

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Auteurs

Zsolt Szűcs (Z)

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

Ilona Bereczki (I)

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

Erzsébet Rőth (E)

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

Márton Milánkovits (M)

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

Eszter Ostorházi (E)

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

Gyula Batta (G)

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

Lajos Nagy (L)

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

Zsuzsanna Dombrádi (Z)

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

Anikó Borbás (A)

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

Pál Herczegh (P)

Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, Egyetem tér 1, H-4032, Hungary. herczeghp@gmail.com.

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Classifications MeSH