Solving the supply of resveratrol tetramers from Papua New Guinean rainforest anisoptera species that inhibit bacterial type III secretion systems
Autor: | Peter Conrad Healy, Ronald J. Quinn, Mikael Elofsson, Melissa Sykes, Xinzhou Yang, Rohan A. Davis, Karren D. Beattie, Charlotta Sundin, Sheng Yin, Min Xu, Harish Holla, Vicky M. Avery, Todd Shelper |
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Rok vydání: | 2014 |
Předmět: |
Rainforest
Odonata Pharmaceutical Science Microbial Sensitivity Tests Resveratrol Heterocyclic Compounds 4 or More Rings Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Inhibitory Concentration 50 Papua New Guinea Biotransformation Phenols Drug Discovery Stilbenes Animals Secretion Biological sciences 030304 developmental biology Benzofurans Pharmacology 0303 health sciences biology 030306 microbiology Chemistry Organic Chemistry Papua New Guinean biology.organism_classification Anti-Bacterial Agents Dipterocarpaceae Complementary and alternative medicine Biochemistry Yersinia pseudotuberculosis Molecular Medicine Anisoptera |
Zdroj: | Journal of natural products. 77(12) |
ISSN: | 1520-6025 |
Popis: | The supply of (-)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screening of a prefractionated 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 μM in a luminescent reporter-gene assay (YopE) and IC50 values of 2.9, 4.5, and 3.3 μM in an enzyme-based 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 target bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (-)-hopeaphenol (1). |
Databáze: | OpenAIRE |
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