New Advances with C20-Diterpenoid Alkaloids as Anticancer Agents
The cytotoxicity against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines was investigated for various types of novel derivatives of diterpenoid alkaloids. Novel derivatives prepared from C20-diterpenoid alkaloids showed significant suppressive effects against all human tumor cell lines tested. Nine acylated C20-diterpenoid alkaloid derivatives were found to be the most potent cytotoxic derivatives against human tumor cell lines (ED50 < 9µM). For atisine-type alkaloids, the presence of an acyl group at both C-11 and C-15 resulted enhanced activity compared with the parent alkaloids that have hydroxy groups at these positions, and the presence of a hydroxy group at the C-6 position was required for the maximal cytotoxic effects. 6,11-Diveratroylpseudokobusine and 6,15-diveratroylpseudokobusine appear to be promising new leads for further development into antitumor agents as these compounds exhibited stronger inhibitory activity against KB-VIN cells than KB cells.