Planta Med 2014; 80 - PD11
DOI: 10.1055/s-0034-1382432

Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei

Y Ren 1, DD Lantvit 2, Y Deng 3, R Kanagasabai 4, JC Gallucci 5, TN Ninh 6, HB Chai 1, DD Soejarto 2, 7, JR Fuchs 1, JC Yalowich 4, J Yu 3, 8, SM Swanson 2, AD Kinghorn 1
  • 1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210
  • 2Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612
  • 3Division of Hematology, Department of Internal Medicine, College of Medicine
  • 4Division of Pharmacology, College of Pharmacy
  • 5Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210
  • 6Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
  • 7Department of Botany, Field Museum of Natural History, Chicago, IL 60605
  • 8Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210

Two new and six known arylnaphthalene lignan lactones were discovered from Phyllanthus poilanei Beille (Phyllanthaceae) collected in South Vietnam. The structures of the new compounds were determined by interpretation of their spectroscopic data, with the structure of one of these new compounds, phyllanthusmin D, being confirmed by single-crystal X-ray diffraction analysis. Several of these compounds were cytotoxic toward the HT-29 human colon cancer cells, with phyllanthusmin D found to be potently cytotoxic in vitro showing an IC50 value of 170 nM and active when tested in an in vivo hollow fiber assay. This compound showed a different mechanism of action when compared with etoposide. It mediated its cytotoxicity toward the HT-29 cells by induction of tumor cell apoptosis through activation of caspase-3 with no inhibitory activity against DNA topoisomerase IIα.