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

Author:
Wibowo, Mario, Wang, Qian, Holst, Jeff, White, Jonathan M., Hofmann, Andreas, Davis, Rohan A.
Source:
Phytochemistry 2018 v.148 pp. 71-77
ISSN:
0031-9422
Subject:
Maytenus, X-ray diffraction, amino acid transporters, chemical constituents of plants, human cell lines, humans, inhibitory concentration 50, leucine, nuclear magnetic resonance spectroscopy, prostatic neoplasms, rain forests, roots, sesquiterpenoids, trees
Abstract:
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.
Agid:
5906696