Dihydro-β-agarofurans from the roots of the Australian endemic rainforest tree Maytenus bilocularis act as leucine transport inhibitors

• Published in: Phytochemistry (Oxford) Vol. 148; pp. 71 - 77
• Main Authors: Wibowo, Mario, Wang, Qian, Holst, Jeff, White, Jonathan M., Hofmann, Andreas, Davis, Rohan A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.04.2018; Elsevier
• Subjects: Australia; Bilocularin; Biochemistry & Molecular Biology; Celastraceae; Celastraceae - chemistry; Crystallography, X-Ray; Dihydro-β-agarofuran; Humans; Leucine - metabolism; Leucine uptake inhibitor; Life Sciences & Biomedicine; Maytenus - chemistry; Maytenus bilocularis; Molecular Structure; Plant Roots - chemistry; Plant Sciences; Prostate cancer; Rainforest; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenoid; Trees; Triterpenes - chemistry; Triterpenes - isolation & purification; Australia; Bilocularin; QLMJVTDLIWLUOI-LLXAYKLJSA-N; Maytenus bilocularis; Celastraceae; FBNNYUKQUYSKRK-GSCOXUHKSA-N; Leucine uptake inhibitor; AXKSNVSHYUXOCE-ZFGBTTGASA-N; OCPGEQPKVFRZAC-VDNXYZQKSA-N; MPTDJPLQAYWOPO-SPUQCMQWSA-N; Prostate cancer; BMYNLNSJEONNAK-YRNANSCDSA-N; Sesquiterpenoid; Dihydro-β-agarofuran; AMINO-ACID-TRANSPORT; QUINONE-METHIDE; SESQUITERPENOIDS; Dihydro-beta-agarofuran
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2018.01.009

Phytochemical studies of the roots of the Australian plant, Maytenus bilocularis, resulted in the identification of six previously undescribed dihydro-β-agarofuran sesquiterpenoids, bilocularins D–I, along with three known natural products, namely 1α,2α,6β,15-tetraacetoxy-9β-benzoyloxydihydro-β-agarofuran, pristimerin, and celastrol. The structures of all compounds were characterized via analysis of 1D/2D NMR and MS data. The absolute configuration of bilocularin D was defined by X-ray crystallography analysis. Bilocularins D and G, 1α,2α,6β,15-tetraacetoxy-9β-benzoyloxydihydro-β-agarofuran, and celastrol inhibited leucine transport in the human prostate cancer cell line LNCaP with IC50 values ranging from 2.5–27.9 μM, which were more potent than the L-type amino acid transporter (LAT) family inhibitor 2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid (BCH). Bilocularins D–F are the first examples of dihydro-β-agarofurans bearing a hydroxyacetate group. Six previously undescribed dihydro-β-agarofurans (bilocularins D–I) were isolated from the roots of Maytenus bilocularis. Compounds were evaluated for their leucine uptake inhibition in the human prostate cancer cell line, LNCaP. [Display omitted] •Six new compounds (bilocularins D–I) were isolated from Maytenus bilocularis (root).•Bilocularins D–F are the first dihydro-β-agarofurans bearing a hydroxyacetate group.•Several compounds showed inhibitory activity on leucine transport in LNCaP cells.•The IC50 values were ranging from 2.5–27.9 μM.•Absolute configurations were determined via X-ray diffraction and/or ECD studies.