Cytotoxic Lanostanoids from Poria cocos

  • J Nat Prod. 2016 Nov 23;79(11):2805-2813. doi: 10.1021/acs.jnatprod.6b00575.
Kuei-Hung Lai  1  2 ,  Mei-Chin Lu  3  4 ,  Ying-Chi Du  1 ,  Mohamed El-Shazly  1  5 ,  Tung-Ying Wu  1 ,  Yu-Ming Hsu  1 ,  Astrid Henz  2 ,  Juan-Cheng Yang  6  7 ,  Anders Backlund  2 ,  Fang-Rong Chang  1  8  9 ,  Yang-Chang Wu  1  6  7  10
Affiliations
  • 1. Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
  • 2. Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Uppsala, Sweden.
  • 3. Graduate Institute of Marine Biology, National Dong Hwa University , Pingtung 944, Taiwan.
  • 4. National Museum of Marine Biology & Aquarium , Pingtung 944, Taiwan.
  • 5. Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University , Organization of African Unity Street, Abassia, Cairo 11566, Egypt.
  • 6. School of Pharmacy, College of Pharmacy, China Medical University , Taichung 40402, Taiwan.
  • 7. Chinese Medicine Research and Development Center, China Medical University Hospital , Taichung 40447, Taiwan.
  • 8. Cancer Center, Kaohsiung Medical University Hospital , Kaohsiung 80708, Taiwan.
  • 9. Department of Marine Biotechnology and Resources, National Sun Yat-sen University , Kaohsiung 80424, Taiwan.
  • 10. Center for Molecular Medicine, China Medical University Hospital , Taichung 40447, Taiwan.
PMID: 27808511 DOI: 10.1021/acs.jnatprod.6b00575
Abstract

Six new and 16 known lanostanoids were isolated from the sclerotia of Poria cocos. The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (1), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (2), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (3), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid (4), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (5), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (6), based on extensive spectroscopic analyses. The absolute configuration of 4 was determined using Mosher's method. The antiproliferative activity of the isolated compounds (except 3 and 4) 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 an antiproliferative effect on the CCRF-CEM Cancer cell line with IC50 values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid (9) and dehydroeburicoic acid (12) showed antiproliferative effects against Molt 4 (IC50 13.8 and 14.3 μM) and HL 60 (IC50 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from P. cocos suggested that targets Other than topoisomerases may be involved in the antiproliferative activity.