Bioactive Dihydro-β-agarofuran Sesquiterpenoids from the Australian Rainforest Plant Maytenus bilocularis
| Autor: | Colleen C. Nelson, Qian Wang, Mario Wibowo, Jeff Holst, Rohan A. Davis, Claire Levrier, Peter Conrad Healy, Andreas Hofmann, Martin C. Sadowski |
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| Rok vydání: | 2016 |
| Předmět: |
Rainforest
Stereochemistry Maytenus bilocularis Molecular Conformation Pharmaceutical Science Crystallography X-Ray 01 natural sciences Analytical Chemistry Drug Discovery LNCaP Potency Humans Pharmacology Ester derivatives biology Molecular Structure 010405 organic chemistry Chemistry Maytenus Organic Chemistry Australia biology.organism_classification 0104 chemical sciences 010404 medicinal & biomolecular chemistry Complementary and alternative medicine Molecular Medicine Efflux Two-dimensional nuclear magnetic resonance spectroscopy Sesquiterpenes |
| Zdroj: | Journal of natural products. 79(5) |
| ISSN: | 1520-6025 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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