Cytotoxic Lanostanoids from Poria cocos.
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 IC50values 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 (IC5013.8 and 14.3 μM) and HL 60 (IC507.3 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.
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.|Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Uppsala, Sweden.
Kuei-Hung
KH
Lai
Graduate Institute of Marine Biology, National Dong Hwa University , Pingtung 944, Taiwan.|National Museum of Marine Biology & Aquarium , Pingtung 944, Taiwan.
Mei-Chin
MC
Lu
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
Ying-Chi
YC
Du
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.|Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University , Organization of African Unity Street, Abassia, Cairo 11566, Egypt.
Mohamed
M
El-Shazly
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
Tung-Ying
TY
Wu
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
Yu-Ming
YM
Hsu
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Uppsala, Sweden.
Astrid
A
Henz
School of Pharmacy, College of Pharmacy, China Medical University , Taichung 40402, Taiwan.|Chinese Medicine Research and Development Center, China Medical University Hospital , Taichung 40447, Taiwan.
Juan-Cheng
JC
Yang
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Uppsala, Sweden.
Anders
A
Backlund
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.|Cancer Center, Kaohsiung Medical University Hospital , Kaohsiung 80708, Taiwan.|Department of Marine Biotechnology and Resources, National Sun Yat-sen University , Kaohsiung 80424, Taiwan.
Fang-Rong
FR
Chang
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung 807, Taiwan.|School of Pharmacy, College of Pharmacy, China Medical University , Taichung 40402, Taiwan.|Chinese Medicine Research and Development Center, China Medical University Hospital , Taichung 40447, Taiwan.|Center for Molecular Medicine, China Medical University Hospital , Taichung 40447, Taiwan.
Yang-Chang
YC
Wu
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D026942:DNA Topoisomerases / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology; D000070660:Wolfiporia / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D014315:Triterpenes; C547186:dehydroeburicoic acid; C497083:lanostanoid; D007810:Lanosterol; D026942:DNA Topoisomerases; C102487:pachymic acid