Cytotoxic C20 Diterpenoid Alkaloids from the Australian Endemic Rainforest Plant Anopterus macleayanus

被引:24
作者
Levrier, Claire [1 ,2 ]
Sadowski, Martin C. [2 ]
Nelson, Colleen C. [2 ]
Davis, Rohan A. [1 ]
机构
[1] Griffith Univ, Eskitis Inst Drug Discovery, Brisbane, Qld 4111, Australia
[2] Queensland Univ Technol, Princess Alexandra Hosp, Translat Res Inst, Australian Prostate Canc Res Ctr Queensland,Inst, Brisbane, Qld 4102, Australia
来源
JOURNAL OF NATURAL PRODUCTS | 2015年 / 78卷 / 12期
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
ENT-KAURENE TYPE; MARINE SPONGE;
D O I
10.1021/acs.jnatprod.5b00509
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
In order to identify new anticancer compounds from nature, a prefractionated library derived from Australian endemic plants was generated and screened against the prostate cancer cell line LNCaP using a metabolic assay. Fractions from the seeds, leaves, and wood of Anopterus macleayanus showed cytotoxic activity and were subsequently investigated using a combination of bioassay-guided fractionation and mass-directed isolation. This led to the identification of four new diterpenoid alkaloids, 6 alpha-acetoxyanopterine (1), 4'-hydroxy-6 alpha-acetoxyanopterine (2), 4'-hydroxyanopterine (3), and 11 alpha-benzoylanopterine (4), along with four known compounds, anopterine (5), 7 beta-hydroxyanopterine (6), 7 beta,4'-dihydroxyanopterine (7), and 7 beta-hydroxy-11 alpha-benzoylanopterine (8); all compounds were purified as their trifiuoroacetate salt. The chemical structures of 1-8 were elucidated after analysis of 1D/2D NMR and MS data. Compounds 1-8 were evaluated for cytotoxic activity against a panel of human prostate cancer cells (LNCaP, C4-2B, and DuCaP) and nonmalignant cell lines (BPH-1 and WPMY-1), using a live-cell imaging system and a metabolic assay. All compounds showed potent cytotoxicity with IC50 values of <400 nM; compound 1 was the most active natural product from this series, with an IC50 value of 3.1 nM toward the LNCaP cell line. The live-cell imaging assay on 1-8 showed a concentration- and time-dependent effect on the cell morphology and proliferation of LNCaP cells.
引用
收藏
页码:2908 / 2916
页数:9
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