Solving the supply of Resveratrol Tetramers from Papua New Guinean rainforest Anisoptera species (Dipterocarpaceae) that inhibit bacterial type III secretion systems

Davis, Rohan A. and Beattie, Karren D. and Xu, Min and Yang, Xinzhou and Yin, Sheng and Holla, Harish and Healy, Peter C. and Sykes, Melissa and Shelper, Todd and Avery, Vicky M. and Elofsson, Mikael and Sundin, Charlotta and Quinn, Ronald (2014) Solving the supply of Resveratrol Tetramers from Papua New Guinean rainforest Anisoptera species (Dipterocarpaceae) that inhibit bacterial type III secretion systems. Journal of Natural Products, 77 (12). pp. 2633-2640. ISSN 0163-3864

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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).

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2014 American Chemical Society and American Society of Pharmacognosy. Permanent restricted access to published version due to publisher copyright policy.
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - No Department
Date Deposited: 20 Apr 2015 00:56
Last Modified: 20 Apr 2015 00:56
Uncontrolled Keywords: resveratrol; Anisoptera; hopeaphenol; enzymatic hydrolysis; T3SS inhibitors; anti-infectives
Fields of Research : 11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics
03 Chemical Sciences > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules
03 Chemical Sciences > 0305 Organic Chemistry > 030502 Natural Products Chemistry
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970103 Expanding Knowledge in the Chemical Sciences
Identification Number or DOI: 10.1021/np500433z

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