1. Phidianidine A and Synthetic Analogues as Naturally Inspired Marine Antifoulants
- Author
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Karine Réhel, Lindon W. K. Moodie, Johan Svenson, Jannie Staffansson, Christophe Labriere, Hugo Denardou, Gunnar Cervin, Jørn H. Hansen, Henrik Pavia, Claire Hellio, Vijayaragavan Elumalai, Tiffany Le Norcy, Department of Chemistry [Tromsø], University of Tromsø (UiT), Department of Marine Sciences [Gothenburg], University of Gothenburg (GU), Laboratoire de Biotechnologie et Chimie Marines (LBCM), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Uppsala Universitet [Uppsala], Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), RISE Bioscience and Materials/Chemistry and Materials, and RISE Research Institutes of Sweden
- Subjects
Biofouling ,Pharmaceutical Science ,panorama ,01 natural sciences ,Analytical Chemistry ,Indole Alkaloids ,chemistry.chemical_compound ,Marine bacteriophage ,Ascomycota ,Drug Discovery ,Ic50 values ,Animals ,Seawater ,14. Life underwater ,UBO ,Pharmacology ,Oxadiazoles ,Natural product ,010405 organic chemistry ,Chemistry ,ACL ,Organic Chemistry ,Thoracica ,Combinatorial chemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Molecular Medicine ,Chemical defense ,Pharmacophore ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology - Abstract
Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants. Phidianidine A and synthetic analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds displayed inhibitory activities at low micromolar concentrations with IC50 values down to 0.7 μg/mL observed. The settlement study highlights that phidianidine A is a potent natural antifoulant and that the scaffold can be tuned to generate simpler and improved synthetic analogues. The bioactivity is closely linked to the size of the compound and to its basicity. The study also illustrates that active analogues can be prepared in the absence of the natural constrained 1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A was incorporated in a coating and included in antifouling field trials, where it was shown that the coating induced potent inhibition of marine bacteria and microalgae settlement.
- Published
- 2020