Diazo transfer-click reaction route to new, lipophilic teicoplanin and ristocetin aglycon derivatives with high antibacterial and anti-influenza virus activity: an aggregation and receptor binding study

J Med Chem. 2009 Oct 8;52(19):6053-61. doi: 10.1021/jm900950d.

Abstract

Semisynthetic, lipophilic ristocetin and teicoplanin derivatives were prepared starting from ristocetin aglycon and teicoplanin psi-aglycon (N-acetyl-D-glucosaminyl aglycoteicoplanin). The terminal amino functions of the aglycons were converted into azido form by triflic azide. Copper catalyzed 1,3-dipolar cycloaddition reaction with lipophilic alkynes resulted in the title compounds. Two of the teicoplanin derivatives showed very good MIC and MBC values against various Gram-positive bacteria, including vanA enterococci. The aggregation and interaction of a n-decyl derivative with bacterial cell wall components was studied. One of the lipophilic ristocetin derivatives displayed favorable anti-influenza virus activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Antiviral Agents / chemical synthesis*
  • Diazonium Compounds / chemistry*
  • Diazonium Compounds / pharmacology
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemical synthesis
  • Doxorubicin / pharmacology
  • Gram-Positive Bacteria / drug effects
  • Microbial Sensitivity Tests
  • Orthomyxoviridae / drug effects
  • Teicoplanin / analogs & derivatives*
  • Teicoplanin / chemical synthesis
  • Teicoplanin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antiviral Agents
  • Diazonium Compounds
  • ristocetin aglycon
  • Teicoplanin
  • Doxorubicin
  • teicoplanin aglycone