Solving the supply of Resveratrol Tetramers from Papua New Guinean rainforest Anisoptera species (Dipterocarpaceae) that inhibit bacterial type III secretion systems
Article
Article Title | Solving the supply of Resveratrol Tetramers from Papua New Guinean rainforest Anisoptera species (Dipterocarpaceae) that inhibit bacterial type III secretion systems |
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ERA Journal ID | 40471 |
Article Category | Article |
Authors | Davis, Rohan A. (Author), Beattie, Karren D. (Author), Xu, Min (Author), Yang, Xinzhou (Author), Yin, Sheng (Author), Holla, Harish (Author), Healy, Peter C. (Author), Sykes, Melissa (Author), Shelper, Todd (Author), Avery, Vicky M. (Author), Elofsson, Mikael (Author), Sundin, Charlotta (Author) and Quinn, Ronald (Author) |
Journal Title | Journal of Natural Products |
Journal Citation | 77 (12), pp. 2633-2640 |
Number of Pages | 8 |
Year | 2014 |
Place of Publication | Washington, DC. United States |
ISSN | 0163-3864 |
1520-6025 | |
Digital Object Identifier (DOI) | https://doi.org/10.1021/np500433z |
Abstract | The supply of (–)-hopeaphenol was achieved via enzymatic biotransformation in order to provide material for pre-clinical investigation. High-throughput screening of a pre-fractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A. thurifera, and similarly A. polyandra, resulted in three known resveratrol tetramers, (–)-hopeaphenol (1), vatalbinoside A (2) and vaticanol B (3). Compounds 1–3 displayed IC50 values of 8.8, 12.5 and 9.9 M in the reporter-gene assay, and IC50 values of 2.9, 4.5 and 3.3 M in the YopH assay, respectively, which suggested that they could potentially act against the T3SS in Yersinia. The structures of 1-3 were confirmed through a combination of spectrometric, chemical methods and single crystal X-ray structure determinations of the natural product 1 and the permethyl ether analogue of 3. The enzymatic hydrolysis of the β-glycoside 2 to the aglycone 1 was achieved through biotransformation using the endogenous leaf enzymes, this significantly enhanced the yield of the desired bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (–)-hopeaphenol (1). |
Keywords | resveratrol; Anisoptera; hopeaphenol; enzymatic hydrolysis; T3SS inhibitors; anti-infectives |
ANZSRC Field of Research 2020 | 321402. Clinical pharmacology and therapeutics |
340401. Biologically active molecules | |
340502. Natural products and bioactive compounds | |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | Griffith University |
Umea University, Sweden | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q28qy/solving-the-supply-of-resveratrol-tetramers-from-papua-new-guinean-rainforest-anisoptera-species-dipterocarpaceae-that-inhibit-bacterial-type-iii-secretion-systems
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