Planta Med 2015; 81 - PM_104
DOI: 10.1055/s-0035-1565481

Antileukemic lanostanoids from Poria cocos

KH Lai 1, 2, A Backlund 2, MC Lu 3, 4, YC Du 1, M El-Shazly 1, 5, TY Wu 1, YM Hsu 1, A Henz 2, FR Chang 1, 6, 7, 8, YC Wu 1, 9, 10, 11
  • 1Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 2Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
  • 3Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan
  • 4National Museum of Marine Biology & Aquarium, Pingtung, Taiwan
  • 5Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo, Egypt
  • 6Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 7Research Center for Natural Product and New Drug, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
  • 9School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan
  • 10Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
  • 11Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan

Seven new lanostanoids, isolated from the sclerotia of Poria cocos, were elucidated to be (20ξ)-16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (1), (20ξ)-3β, 16α, 29-trihydroxy-24-methyllanosta-7, 9(11), 24(31)-trien-21-oic acid (2), (20ξ)-3β, 16α, 30-trihydroxy-24-methyllanosta-7, 9(11), 24(31)-trien-21-oic acid (3), (20ξ)-3β-acetyloxy-16α, 24α-dihydroxy-lanosta-7, 9(11), 25-trien-21-oic acid (4), (20ξ)-5α, 8α-epidioxy-3-O-hydroxyacetoxy-3β, 16α-dihydroxy-24-methyllanosta-6, 9(11), 24(31)-trien-21-oic acid (5), (20ξ)-3β, 16α-dihydroxy-7-oxo-24-methyllanosta-8, 24(31)-dien-21-oic acid (6) and (20ξ)-3α, 16α-dihydroxy-7-oxo-24-methyllanosta-8, 24(31)-dien-21-oic acid (7), based on the extensive spectroscopic analyses. The antileukemic activity of the new compounds (except 3 and 4), along with the fifteen known lanostane-type triterpenoids, was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60 and K562). Dehydropachymic acid (9), dehydroeburicoic acid (12), pachymic acid (14) and lanosta-7, 9(11), 24-trien-21-oic acid (20) exhibited cytotoxic effect on CCRF-CEM cancer cell line with IC50 values of 1.43, 2.96, 2.61 and 5.96 µg/mL, respectively. Both dehydropachymic acid (9) and dehydroeburicoic acid (12) showed cytotoxicity against Molt 4 (IC50 7.26 and 6.67 µg/mL) and HL 60 (IC50 3.84 and 2.79 µg/mL) leukemic cell lines. ChemGPS-NP analysis on the active lanostanoids from P. cocos suggested that targets other than topoisomerases may be involved in the cytotoxic effect.