A few atoms make the difference

Synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives

Ilona Bereczki, Attila Mándi, Erzsébet RÅ'Th, A. Borbás, Ádám Fizil, I. Komáromi, Attila Sipos, T. Kurtán, G. Batta, Eszter Ostorházi, F. Rozgonyi, Evelien Vanderlinden, Lieve Naesens, F. Sztaricskai, P. Herczegh

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silico conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity.

Original languageEnglish
Pages (from-to)73-86
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume94
DOIs
Publication statusPublished - Apr 13 2015

Fingerprint

Teicoplanin
Glycopeptides
Orthomyxoviridae
Antiviral Agents
Viruses
Nuclear magnetic resonance
Anti-Bacterial Agents
Derivatives
Atoms
Ristocetin
Conformations
Structure-Activity Relationship
Circular Dichroism
Computer Simulation
Bioactivity

Keywords

  • Antibacterial
  • Antiviral
  • Conformation
  • Ristocetin aglycon
  • Teicoplanin aglycon

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

A few atoms make the difference : Synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives. / Bereczki, Ilona; Mándi, Attila; RÅ'Th, Erzsébet; Borbás, A.; Fizil, Ádám; Komáromi, I.; Sipos, Attila; Kurtán, T.; Batta, G.; Ostorházi, Eszter; Rozgonyi, F.; Vanderlinden, Evelien; Naesens, Lieve; Sztaricskai, F.; Herczegh, P.

In: European Journal of Medicinal Chemistry, Vol. 94, 13.04.2015, p. 73-86.

Research output: Contribution to journalArticle

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