Synthesis and studies of anticancer properties of lupane-type triterpenoid derivatives containing a cisplatin fragment

• A new series of betulinic acid–cisplatin conjugates were synthesized.
• Cytotoxicity and selectivity were assessed against five different tumor cell lines and one non-tumor cell line.
• The aim was to combine two structural units, both related with apoptosis induction.
• Interestingly, betulinic acid–cisplatin conjugates were less cytotoxic than the precursors.

Both betulinic acid 1 and cisplatin are promising antitumor agents, which induce apoptotic cell death of cancer cells. In the present investigation a new series of betulinic acid–cisplatin conjugates were synthesized and cytotoxicity and selectivity were assessed against five different tumor cell lines. The aim was to combine two structural units, both related with apoptosis induction. The derivatives exerted a dose-dependent antiproliferative action at micromolar concentrations and the effect of these structural variations on anticancer activity was studied and discussed. Several compounds revealed significant antitumor activity, as the most active substance 3-O-acetylbetulinic (2-(2-aminoethyl)aminoethyl)amide (IC50 = 1.30–2.24 μM). Interestingly, Betulinic acid–cisplatin conjugates were less cytotoxic than the precursors.

Figure optionsDownload as PowerPoint slide