Structure-toxicity relationship of aminoglycosides: correlation of 2'-amine basicity with acute toxicity in pseudo-disaccharide scaffolds

Bioorg Med Chem. 2008 Oct 1;16(19):8940-51. doi: 10.1016/j.bmc.2008.08.053. Epub 2008 Aug 27.

Abstract

A new pseudo-disaccharide NB23 with a 3',4'-methylidene protection was designed and its properties were evaluated in comparison to other two structurally related pseudo-disaccharides. The basicity of the 2'-amine was found to be well correlated to acute toxicity data in mice: the increase in the basicity is associated with the toxicity increase. Based on these data, a new pseudo-trisaccharide NB45 was constructed. NB45 exhibited significant antibacterial activity while at the same time retained low acute toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Aminoglycosides / chemical synthesis
  • Aminoglycosides / pharmacology
  • Aminoglycosides / toxicity*
  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / toxicity*
  • Disaccharides / chemistry
  • Disaccharides / pharmacology
  • Disaccharides / toxicity*
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Structure-Activity Relationship
  • Toxicity Tests, Acute
  • Trisaccharides / chemistry
  • Trisaccharides / pharmacology
  • Trisaccharides / toxicity*

Substances

  • Amines
  • Aminoglycosides
  • Anti-Bacterial Agents
  • Disaccharides
  • Trisaccharides