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Cytotoxic C20 Diterpenoid Alkaloids from the Australian Endemic Rainforest Plant Anopterus macleayanus
Version 2 2015-12-17, 10:51
Version 1 2015-11-24, 22:11
journal contribution
posted on 2015-12-17, 10:51 authored by Claire Levrier, Martin
C. Sadowski, Colleen C. Nelson, Rohan A. DavisIn 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,
6α-acetoxyanopterine (1), 4′-hydroxy-6α-acetoxyanopterine
(2), 4′-hydroxyanopterine (3), and
11α-benzoylanopterine (4), along with four known
compounds, anopterine (5), 7β-hydroxyanopterine
(6), 7β,4′-dihydroxyanopterine (7), and 7β-hydroxy-11α-benzoylanopterine (8); all compounds were purified as their trifluoroacetate 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.