title: Cytotoxic C20 Diterpenoid Alkaloids from the Australian Endemic Rainforest Plant Anopterus macleayanus.
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.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.|Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute , Brisbane, QLD 4102, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Levrier
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute , Brisbane, QLD 4102, Australia.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Sadowski
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute , Brisbane, QLD 4102, Australia.
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001315:Australia; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy; D065947:Rainforest; D012639:Seeds / Q000737:chemistry; D014934:Wood / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes