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Dihydro‐ β ‐agarofurans from the Australian Endemic Rainforest Plant Denhamia pittosporoides Inhibit Leucine Transport in Prostate Cancer Cells
Author(s) -
Wibowo Mario,
Wang Qian,
Holst Jeff,
White Jonathan M.,
Hofmann Andreas,
Davis Rohan A.
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600462
Subject(s) - lncap , chemistry , rainforest , stereochemistry , celastraceae , absolute configuration , cancer cell lines , amino acid transporter , prostate cancer , biochemistry , transporter , botany , cancer cell , cancer , biology , gene , genetics
Two previously unknown dihydro‐ β ‐agarofuran sesquiterpenoids, denhaminol I ( 1 ) and denhaminol J ( 2 ), together with four related and known metabolites, 1 α ,2 α ,6 β ,15‐tetraacetoxy‐9 α ‐benzoyloxy‐8‐oxodihydro‐ β ‐agarofuran ( 3 ), wilforsinine F ( 4 ), 1 α ,2 α ,6 β ,8 α ,15‐pentaacetoxy‐9 α ‐benzoyloxydihydro‐ β ‐agarofuran ( 5 ), and 1 α ,2 α ,6 β ,15‐tetraacetoxy‐9 β ‐benzoyloxydihydro‐ β ‐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/2D NMR 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 IC 50 values of 51.5 and 95.5 μ m , 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‐ β ‐agarofurans from D. pittosporoides .