2. Academic Validation
  3. Generation of Stilbene Antimicrobials against Multiresistant Strains of Staphylococcus aureus through Biotransformation by the Enzymatic Secretome of Botrytis cinerea

Generation of Stilbene Antimicrobials against Multiresistant Strains of Staphylococcus aureus through Biotransformation by the Enzymatic Secretome of Botrytis cinerea

  • J Nat Prod. 2020 Aug 28;83(8):2347-2356. doi: 10.1021/acs.jnatprod.0c00071.
Davide Righi 1 2,  Robin Huber 1 2,  Alexey Koval 3,  Laurence Marcourt 1 2,  Sylvain Schnee 4,  Anaïs Le Floch 1 2,  Verena Ducret 5,  Remo Perozzo 1 2,  Concetta C de Ruvo 1 2,  Nicole Lecoultre 4,  Emilie Michellod 4,  Samad N Ebrahimi 6,  Elisabeth Rivara-Minten 1 2,  Vladimir L Katanaev 3 7,  Karl Perron 5,  Jean-Luc Wolfender 1 2,  Katia Gindro 4,  Emerson F Queiroz 1 2
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.
  • 2 Institute of Pharmaceutical Sciences of Western Switzerland (ISPSW), University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.
  • 3 Department of Cell Physiology and Metabolism, Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.
  • 4 Plant Protection Research Division, Mycology Group, Agroscope, Route de Duillier 50, P.O. Box 1012, 1260 Nyon, Switzerland.
  • 5 Microbiological Analysis Platform, Microbiology Unit, Department of Botany and Plant Biology, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
  • 6 Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
  • 7 School of Biomedicine, Far Eastern Federal University, Vladivostok 690090, Russia.
PMID: 32705864 DOI: 10.1021/acs.jnatprod.0c00071
Abstract

The biotransformation of a mixture of resveratrol and pterostilbene was performed by the protein secretome of Botrytis cinerea. Several reaction conditions were tested to overcome solubility issues and to improve enzymatic activity. Using MeOH as cosolvent, a series of unusual methoxylated compounds was generated. The reaction was scaled-up, and the resulting mixture purified by semipreparative HPLC-PDA-ELSD-MS. Using this approach, 15 analogues were isolated in one step. Upon full characterization by NMR and HRMS analyses, eight of the compounds were new. The Antibacterial activities of the isolated compounds were evaluated in vitro against the opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus. The selectivity index was calculated based on cytotoxic assays performed against human liver carcinoma cells (HepG2) and the human breast epithelial cell line (MCF10A). Some compounds revealed remarkable Antibacterial activity against multidrug-resistant strains of S. aureus with moderate human cell line cytotoxicity.

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