Bioactive Dihydro-β-agarofuran Sesquiterpenoids from the Australian Rainforest Plant Maytenus bilocularis

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Wibowo, Mario
Levrier, Claire
Sadowski, Martin C
Nelson, Colleen C
Wang, Qian
Holst, Jeff
Healy, Peter C
Hofmann, Andreas
Davis, Rohan A
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2016
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Abstract

Chemical investigations of the CH2Cl2 extract obtained from the leaves of the Australian rainforest tree Maytenus bilocularis afforded three new dihydro-β-agarofurans, bilocularins A–C (1–3), and six known congeners, namely, celastrine A (4), 1α,6β,8α-triacetoxy-9α-benzoyloxydihydro-β-agarofuran (5), 1α,6β-diacetoxy-9α-benzoyloxy-8α-hydroxydihydro-β-agarofuran (6), Ejap-10 (11), 1α,6β-diacetoxy-9β-benzoyloxydihydro-β-agarofuran (12), and Ejap-2 (13). The major compound 1 was used in semisynthetic studies to afford four ester derivatives (7–10). The chemical structures of 1–3 were elucidated following analysis of 1D/2D NMR and MS data. The absolute configurations of bilocularins A (1) and B (2) were determined by single-crystal X-ray diffraction analysis. All compounds were evaluated for cytotoxic activity against the human prostate cancer cell line LNCaP; none of the compounds were active. However, several compounds showed similar potency to the drug efflux pump inhibitor verapamil in reversing the drug resistance of the human leukemia CEM/VCR R cell line. In addition, similar to verapamil, compound 5 was found to inhibit leucine uptake in LNCaP cells (IC50 = 15.5 μM), which was more potent than the leucine analogue 2-aminobicyclo[2.2.1]heptane-2-carbocyclic acid. This is the first report of secondary metabolites from Maytenus bilocularis.

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Journal of Natural Products

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79

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Natural Products, copyright 2016 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see 10.1021/acs.jnatprod.6b00190.

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Chemical sciences

Other chemical sciences not elsewhere classified

Biological sciences

Biomedical and clinical sciences

Traditional, complementary and integrative medicine

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