Generation of potent antibacterial compounds through enzymatic and chemical modifications of the <i>trans-δ</i>-viniferin scaffold

Article Article scientifique Article Generation of potent antibacterial compounds through enzymatic and chemical modifications of the <i>trans-δ</i>-viniferin scaffold eng 2023-09-25 2023-09-25 author Huber Robin School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland. 402520 author Marcourt Laurence 0000-0002-9614-1099 School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland. 729234 Section des sciences pharmaceutiques (FARMA) author Heritier Margaux School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland. 835570 author Luscher Alexandre 0009-0002-9247-7713 Department of Microbiology and Molecular Medicine, University of Geneva, Rue Michel-Servet 1, 1211, Genève 4, Switzerland. 660541 Département de médecine (DEMED) author Guebey Laurie Department of Microbiology and Molecular Medicine, University of Geneva, Rue Michel-Servet 1, 1211, Genève 4, Switzerland. 834878 author Schnee Sylvain Agroscope, Plant Protection Research Division, Mycology Group, Route de Duillier 50, P.O. Box 1012, 1260, Nyon, Switzerland. author Michellod Emilie Agroscope, Plant Protection Research Division, Mycology Group, Route de Duillier 50, P.O. Box 1012, 1260, Nyon, Switzerland. author Guerrier Stéphane School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland.,Geneva School of Economics and Management, University of Geneva, 1205, Geneva, Switzerland. 625357 Services communs du département des sciences de la terre (DETCO) author Wolfender Jean-Luc School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland. 135649 Section des sciences pharmaceutiques (FARMA) author Scapozza Leonardo School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland. 600318 Section des sciences pharmaceutiques (FARMA) author Kohler Thilo 0000-0003-4889-9492 Department of Microbiology and Molecular Medicine, University of Geneva, Rue Michel-Servet 1, 1211, Genève 4, Switzerland. 23327 author Gindro Katia 0000-0003-4344-1853 Agroscope, Plant Protection Research Division, Mycology Group, Route de Duillier 50, P.O. Box 1012, 1260, Nyon, Switzerland. katia.gindro@agroscope.admin.ch. author Ferreira Queiroz Emerson School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland. emerson.ferreira@unige.ch.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland. emerson.ferreira@unige.ch. 135675 Section des sciences pharmaceutiques (FARMA) 21 15986 10.1038/s41598-023-43000-5 37749179 2045-2322 PMC10520035 https://www.nature.com/articles/s41598-023-43000-5 Stilbene dimers are well-known for their diverse biological activities. In particular, previous studies have demonstrated the high antibacterial potential of a series of trans-δ-viniferin-related compounds against gram-positive bacteria such as Staphylococcus aureus. The trans-δ-viniferin scaffold has multiple chemical functions and can therefore be modified in various ways to generate derivatives. Here we report the synthesis of 40 derivatives obtained by light isomerization, O-methylation, halogenation and dimerization of other stilbene monomers. The antibacterial activities of all generated trans-δ-viniferin derivatives were evaluated against S. aureus and information on their structure-activity relationships (SAR) was obtained using a linear regression model. Our results show how several parameters, such as the O-methylation pattern and the presence of halogen atoms at specific positions, can determine the antibacterial activity. Taken together, these results can serve as a starting point for further SAR investigations. Staphylococcus aureus Anti-Bacterial Agents / pharmacology Benzofurans / pharmacology Dimerization Resorcinols Stilbenes Dewey 310 Dewey 615 Dewey 616 Swiss National Science Foundation Improving natural products chemical biodiversity for drug discovery by fungal secretome assisted biotransformation 182438 CH Swiss National Science Foundation NMR 600MHz for metabolomics and biomarker identification for life sciences, chemical biology and medical projects at the University of Geneva 164095 CH 31 Section des sciences pharmaceutiques 17 54 Département de microbiologie et médecine moléculaire 21B 117 Research Center for Statistics S5 false 882 Phytochimie et produits naturels bioactifs 235 Perception du Quorum et gènes de virulence 301 880 Biochimie pharmaceutique https://yareta.unige.ch/archives/a2fbdc04-48e5-4e74-8dcf-c8f6fa688ec2 Scientific reports 13 1 9d96a2ef-0f08-4f93-b780-70505bc5be42 Article (Published version) Public Article_scientifique_from_unpaywall.pdf 2065338 application/pdf CC BY-4.0 98cd1133bbf22119d502d1eefd3da66a37491c894bb0ff9f0f364581fe79e559 b1598786-300f-432e-8850-d843ad7d5706 Appendix Public 41598_2023_43000_MOESM1_ESM.pdf 12398175 application/pdf c29f3625195dd41510fb57e512f9fe8f2aafbafd70a0ef86b095ad9c769d015b openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté d'économie et de management / Research Center for Statistics

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Discovery of anti-infective compounds against Mycobacterium marinum after biotransformation of simple natural stilbene scaffolds by a fungal secretome		2024	25	147
Generation of potent antibacterial compounds through enzymatic and chemical modifications of the trans-δ-viniferin scaffold	Scientific reports	2023	2	0

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Huber, Robin