Hydrazino-aza and N-azapeptoids with therapeutic potential as anticancer agents

Bioorg Med Chem. 2003 Nov 17;11(23):4881-9. doi: 10.1016/j.bmc.2003.09.018.

Abstract

The ubiquitin-proteasome-mediated degradation pathway plays an important role in regulating protein turnover in eucaryotic cells and, consequently, regulates both cell proliferation and cell death. The proteasome influences many cellular regulatory signals and is thus a potential target for pharmacological agents. The study of proteasome function has led to the identification of several natural and synthetic compounds that can act as tumor cell growth inhibitors. In this study, we have developed a series of hydrazino-aza and N-azapeptoids, analogues of Ac-Leucyl-Leucyl-Norleucinal (ALLN) a non-specific peptidyl aldehyde inhibitor of the proteasome. These peptide analogues share a common backbone and bear different C- and N-terminal functions. Their antiproliferative activity on murine leukemia L1210 cells is reported here.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology
  • Aza Compounds / therapeutic use*
  • Cell Line, Tumor
  • Hydrazines / chemistry*
  • Leukemia L1210 / pathology
  • Magnetic Resonance Spectroscopy
  • Mice
  • Peptoids / chemistry*

Substances

  • Antineoplastic Agents
  • Aza Compounds
  • Hydrazines
  • Peptoids