Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3220-4. doi: 10.1016/j.bmcl.2009.04.103. Epub 2009 May 3.

Abstract

A series of boron peptides 11, 13, 15 and 17 were designed and synthesized as proteasome inhibitors based on the structure of Belactosin C. Matteson homologation was a key step in the synthesis of the boron peptides. Compounds 11a and 13 showed significant inhibition of 20S proteasome chymotrypsin-like (beta5) activity (IC(50)=0.28 and 0.51 microM, respectively). Furthermore, like PS-341, compound 11a increased the G2/M cell distribution. A biparametric cytofluorimetric analysis with FITC-labeled annexin V and propidium iodide showed induction of apoptosis by compound 11a at >1 microM concentrations of compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents
  • Apoptosis / drug effects
  • Boron*
  • Chymotrypsin
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • G2 Phase / drug effects
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Proteasome Inhibitors*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Peptides
  • Proteasome Inhibitors
  • belactosin C
  • Chymotrypsin
  • Boron