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

Levrier, Claire, Sadowski, Martin C., Nelson, Colleen C., & Davis, Rohan A. (2015) Cytotoxic C20 Diterpenoid Alkaloids from the Australian Endemic Rainforest Plant Anopterus macleayanus. Journal of Natural Products, 78(12), pp. 2908-2916.

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Abstract

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, 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.

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ID Code: 97738
Item Type: Journal Article
Refereed: Yes
Additional URLs:
DOI: 10.1021/acs.jnatprod.5b00509
ISSN: 1520-6025
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 American Chemical Society and
American Society of Pharmacognosy
Copyright Statement: This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Deposited On: 31 Jul 2016 23:53
Last Modified: 02 Aug 2016 04:09

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