145
Views
1
CrossRef citations to date
0
Altmetric
Patent Evaluations

Glycopeptide antibiotic analogs efficient against vancomycin-resistant bacteria: a patent evaluation (WO2013022763)

&
Pages 1625-1634 | Published online: 23 Aug 2013
 

Abstract

The patent claims the preparation of vancomycin analogs equally active against bacterial strains that are primarily sensitive or resistant to this antibiotic. The pseudopeptide core of new compounds carries the amidine group that replaces the carboxamide linking group in the D ring-bearing amino acid residue of the glycopeptide. An elegant method of synthesis of amidine containing glycopeptides via thioamides was developed. The key glycopeptide thioamide analogs were prepared by total multistep synthesis. These analogs can be readily converted to the antibiotic's amidine as well as to alkylamidines, amidrazones, hydroxyamidines and similar analogs. The new analogs are capable of circumventing bacterial resistance derived from the D-Ala-D-Ala to D-Ala-D-Lac alteration – the mechanism operational in the resistant strains VanA and VanB. The interaction of the carboxamide, thioamide and amidine fragments of vancomycin analogs with the targets in resistant and sensitive bacteria was investigated. The novel compounds demonstrated potent activity against VanA-resistant bacteria Enterococcus faecalis (minimal inhibitory concentration = 0.3 − 0.6 μg/ml). However data on susceptible strains and resistant clinical isolates are lacking to further document the interest of the compounds. The results provide evidence for structural modifications that can improve the therapeutic efficacy of vancomycin, in particular, for treatment of vancomycin-resistant infections.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 99.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,757.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.