Cytotoxic betulin-derived hydroxypropargylamines trigger apoptosis.

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.