Dihydro-beta-agarofurans from the Australian Endemic Rainforest Plant Denhamia pittosporoides Inhibit Leucine Transport in Prostate Cancer Cells

作者：Wibowo Mario; Wang Qian; Holst Jeff; White Jonathan M; Hofmann Andreas; Davis Rohan A

来源：Asian Journal of Organic Chemistry, 2016, 5(12): 1461-1466.

DOI：10.1002/ajoc.201600462

• cancer
• dihydro-beta-agarofurans
• heterocycles
• inhibitors
• natural products

Two previously unknown dihydro-beta-agarofuran sesquiterpenoids, denhaminolI (1) and denhaminolJ (2), together with four related and known metabolites, 1,2,6,15-tetraacetoxy-9-benzoyloxy-8-oxodihydro--agarofuran (3), wilforsinineF (4), 1,2,6,8,15-pentaacetoxy-9-benzoyloxydihydro--agarofuran (5), and 1,2,6,15-tetraacetoxy-9-benzoyloxydihydro--agarofuran (6), were isolated from the leaves of an Australian rainforest plant, Denhamia pittosporoides. The structures of compounds 1 and 2 were determined by analysis of their 1D/2DNMR and MS data. The absolute configuration of compound 1 was established by single-crystal X-ray diffraction analysis. Compounds 1 and 4 were shown to inhibit leucine transport in the human prostate cancer cell line LNCaP, with IC50 values of 51.5 and 95.5m, respectively. Both compounds 1 and 4 were more potent than the l-type amino acid transporter (LAT) family inhibitor 2-aminobicyclo[2.2.1]-heptane-2-carboxylic acid (BCH). This is the first report of dihydro--agarofurans from D.pittosporoides.

• 出版日期2016-12