Synthesis and evaluation of fluorogenic 2-amino-1,8-naphthyridine derivatives for the detection of bacteria

Org Biomol Chem. 2012 Apr 7;10(13):2578-89. doi: 10.1039/c2ob06986e. Epub 2012 Feb 22.

Abstract

Several novel fluorogenic N-aminoacylnaphthyridine substrates were synthesized in good yield and tested for their ability to detect pathogenic bacteria in agar-based cell culture. Simple 2-N-(β-alanyl)amino-5,7-dialkylnaphthyridine substrates were selectively hydrolysed by β-alanylaminopeptidase expressing bacteria, but were subject to diffusion in the agar medium. Diffusion was reduced in the 2-N-(β-alanyl)amino-7-alkylnaphthyridine substrates with longer alkyl chains, but inhibition of growth was increased. 2-N-(β-Alanyl)amino-7-octylnaphthyridine inhibited the growth of all species tested, except for strains resistant to colistin/polymyxin, providing a rationale for the development of substrates for the selective detection of drug resistant species in clinical samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / metabolism
  • Bacteria / chemistry
  • Bacteria / isolation & purification
  • Fluorescent Dyes / chemistry*
  • Molecular Structure
  • Naphthyridines / chemistry*
  • Naphthyridines / metabolism
  • Peptides / chemistry
  • Structure-Activity Relationship

Substances

  • 2-amino-1,8-naphthyridine
  • Fluorescent Dyes
  • Naphthyridines
  • Peptides
  • Aminopeptidases