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Solving the supply of resveratrol tetramers from Papua New Guinean rainforest anisoptera species that inhibit bacterial type III secretion systems
- Source :
- Journal of natural products. 77(12)
- Publication Year :
- 2014
-
Abstract
- 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).
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15206025
- Volume :
- 77
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of natural products
- Accession number :
- edsair.doi.dedup.....20fc9506585e52cca99ecf54b468b670