Synthesis and biological evaluation of penem inhibitors of bacterial signal peptidase

Bioorg Med Chem Lett. 2009 Jul 15;19(14):3787-90. doi: 10.1016/j.bmcl.2009.04.034. Epub 2009 Apr 18.

Abstract

We report the first synthesis of a 5S penem, known to bind bacterial type I signal peptidase, from the commercially available and inexpensive 6-aminopenicillanic acid. We report the first in vivo activity of the compound and use structure-activity relationship studies to begin to define the determinants of signal peptidase binding and also to begin to optimize the penem as an antibiotic.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Microbial Sensitivity Tests
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / chemical synthesis
  • Penicillanic Acid / chemistry
  • Penicillanic Acid / pharmacology
  • Serine Endopeptidases / metabolism
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Membrane Proteins
  • Serine Proteinase Inhibitors
  • Penicillanic Acid
  • Serine Endopeptidases
  • type I signal peptidase
  • aminopenicillanic acid