Cytotoxic betulin-derived hydroxypropargylamines trigger apoptosis

Bioorg Med Chem. 2013 Jan 15;21(2):425-35. doi: 10.1016/j.bmc.2012.11.016. Epub 2012 Nov 24.

Abstract

Several novel betulin derivatives were prepared and evaluated for their antitumor activity. Among others, 3-O-acetylbetulinic aldehyde served as an ideal starting material for the synthesis of 28-acetylenic derivatives that were further transformed into Mannich bases. These hydroxypropargylamines were screened for their antitumor activity in a panel of nine human cancer cell lines in a sulforhodamine B (SRB) assay. Several compounds showed a noteworthy antitumor activity. The results from acridine orange/propidium iodide staining and annexinV-FITC assays as well as DNA laddering experiments provided evidence for an apoptotic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects*
  • Cell Line
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • Mice
  • NIH 3T3 Cells
  • Pargyline / analogs & derivatives*
  • Pargyline / chemistry
  • Propylamines / chemistry*
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry*
  • Triterpenes / toxicity

Substances

  • Antineoplastic Agents
  • Propylamines
  • Triterpenes
  • propargylamine
  • betulin
  • Pargyline