Planta Med 2013; 79 - PC4
DOI: 10.1055/s-0033-1348560

New Advances with C20-Diterpenoid Alkaloids as Anticancer Agents

K Wada 1, 2, E Ohkoshi 2, KF Bastow 2, KH Lee 3
  • 1Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 1, Katsuraoka-cho, Otaru 047 – 0264, Japan
  • 2Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
  • 3Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA and Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan

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.