Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents

Zsolt Szűcs, Viktor Kelemen, Son Le Thai, Magdolna Csávás, Erzsébet Rőth, G. Batta, Annelies Stevaert, Evelien Vanderlinden, Lieve Naesens, P. Herczegh, A. Borbás

Research output: Contribution to journalArticle

Abstract

Six series of semisynthetic lipophilic glycopeptide antibiotic derivatives were evaluated for in vitro activity against influenza A and B viruses. The new teicoplanin pseudoaglycon-derived lipoglycopeptides were prepared by coupling one or two side chains to the N-terminus of the glycopeptide core, using various conjugation methods. Three series of derivatives bearing two lipophilic groups were synthesized by attaching bis-alkylthio maleimides directly or through linkers of different lengths to the glycopeptide. Access to the fourth and fifth series of compounds was achieved by click chemistry, introducing single alkyl/aryl chains directly or through a tetraethylene glycol linker to the same position. A sixth group of semisynthetic derivatives was obtained by sulfonylation of the N-terminus. Of the 42 lipophilic teicoplanin pseudoaglycon derivatives tested, about half showed broad activity against influenza A and B viruses, with some of them having reasonable or no cytotoxicity. Minor differences in the side chain length as well as lipophilicity appeared to have significant impact on antiviral activity and cytotoxicity. Several lipoglycopeptides were also found to be active against human coronavirus.

Original languageEnglish
Pages (from-to)1017-1030
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume157
DOIs
Publication statusPublished - Sep 5 2018

Fingerprint

Teicoplanin
Glycopeptides
Structure-Activity Relationship
Orthomyxoviridae
Viruses
Influenza B virus
Influenza A virus
Derivatives
Maleimides
Cytotoxicity
Click Chemistry
Coronavirus
Glycols
Bearings (structural)
Antiviral Agents
Chain length
Anti-Bacterial Agents

Keywords

  • Coronavirus
  • Influenza virus inhibitor
  • Lipoglycopeptide
  • Maleimide
  • Sulfonamide
  • Teicoplanin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents. / Szűcs, Zsolt; Kelemen, Viktor; Le Thai, Son; Csávás, Magdolna; Rőth, Erzsébet; Batta, G.; Stevaert, Annelies; Vanderlinden, Evelien; Naesens, Lieve; Herczegh, P.; Borbás, A.

In: European Journal of Medicinal Chemistry, Vol. 157, 05.09.2018, p. 1017-1030.

Research output: Contribution to journalArticle

Szűcs, Zsolt ; Kelemen, Viktor ; Le Thai, Son ; Csávás, Magdolna ; Rőth, Erzsébet ; Batta, G. ; Stevaert, Annelies ; Vanderlinden, Evelien ; Naesens, Lieve ; Herczegh, P. ; Borbás, A. / Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents. In: European Journal of Medicinal Chemistry. 2018 ; Vol. 157. pp. 1017-1030.
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