Small structural changes of pentacyclic lupane type triterpenoid derivatives lead to significant differences in their anticancer properties

In the present investigations five new derivatives of betulinic and betulonic acid were synthesized and the effect of this structural variations on anticancer activity was studied and discussed. The antiproliferative activity of betulinic and betulonic acid derivatives was studied against eight tumor cell lines of different histogenic origin. The derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. The apoptotic mode of cell death on colon cancer cell line HT-29 was induced by the most active compounds 5, 2-amino-3-hydroxy-2-(hydroxymethyl)propyl (3- O-acetyl)betulinate, and 9, 2-amino-3-hydroxy-2-(hydroxymethyl)propyl betulonate. Treatment of HT-29 cells with 5 and 9 induced apoptosis, as observed by dye exclusion test (trypan blue) and by the appearance of a typical ladder pattern in the DNA fragmentation assay and FITC annexin V assay. Cell cycle perturbations caused by compound 5 are also presented. Synthesis, characterization and in vitro antitumoral activity of novel betulinic ( 1) and betulonic acid ( 2) derivatives against eight tumor cell lines of different histogenic origin has been carried out. Furthermore, structure activity relationships and mode of cell death are described. The drastic influence of minor structural changes on the anticancer properties is shown. [Display omitted]