Selectively guanidinylated derivatives of neamine. Syntheses and inhibition of anthrax lethal factor protease

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5183-9. doi: 10.1016/j.bmcl.2006.07.005. Epub 2006 Jul 25.

Abstract

A series of mono-, di-, and tri-guanidinylated derivatives of neamine were prepared via selective guanidinylation of neamine. These molecules represent a novel scaffold as inhibitors of anthrax lethal factor zinc metalloprotease. Methods for the synthesis of these compounds are described, and structure-activity relationships among the series are analyzed. In addition, initial findings regarding the mechanism of LF inhibition for these molecules are presented.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aminoglycosides / chemical synthesis*
  • Aminoglycosides / pharmacology*
  • Antigens, Bacterial
  • Bacillus anthracis / enzymology
  • Bacterial Toxins / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Framycetin / chemical synthesis*
  • Framycetin / pharmacology*
  • Guanidine / chemistry
  • Kinetics
  • Metalloendopeptidases / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Aminoglycosides
  • Antigens, Bacterial
  • Bacterial Toxins
  • Enzyme Inhibitors
  • anthrax toxin
  • Framycetin
  • neamine
  • Metalloendopeptidases
  • Guanidine