Synthesis and antibacterial properties under blue LED light of conjugates between the siderophore desferrioxamine B (DFOB) and an Iridium(III) complex.

Autor: Faucon A; CNRS, UMR7242 Biotechnologie et Signalisation Cellulaire, 300 Boulevard Sébastien Brant, F-67412 Illkirch, Strasbourg, France; Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg (IREBS), 300 Boulevard Sébastien Brant, F-67412 Illkirch, Strasbourg, France., Renault J; Normandie University, LCMT, ENSICAEN, UNICAEN, CNRS, 6 Bd du Maréchal Juin, 14050 Caen, France., Josts I; The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR), 22761 Hamburg, Germany; Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, 22761 Hamburg, Germany., Couchot J; Université de Franche-Comté, UMR6249 CNRS Chrono-environnement, F-25000 Besançon, France., Renaud JL; Normandie University, LCMT, ENSICAEN, UNICAEN, CNRS, 6 Bd du Maréchal Juin, 14050 Caen, France; Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 75005 Paris, France., Hoegy F; CNRS, UMR7242 Biotechnologie et Signalisation Cellulaire, 300 Boulevard Sébastien Brant, F-67412 Illkirch, Strasbourg, France; Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg (IREBS), 300 Boulevard Sébastien Brant, F-67412 Illkirch, Strasbourg, France., Plésiat P; Université de Franche-Comté, UMR6249 CNRS Chrono-environnement, F-25000 Besançon, France., Tidow H; The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR), 22761 Hamburg, Germany; Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, 22761 Hamburg, Germany., Gaillard S; Normandie University, LCMT, ENSICAEN, UNICAEN, CNRS, 6 Bd du Maréchal Juin, 14050 Caen, France., Mislin GLA; CNRS, UMR7242 Biotechnologie et Signalisation Cellulaire, 300 Boulevard Sébastien Brant, F-67412 Illkirch, Strasbourg, France; Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg (IREBS), 300 Boulevard Sébastien Brant, F-67412 Illkirch, Strasbourg, France. Electronic address: mislin@unistra.fr.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Oct 01; Vol. 112, pp. 117842. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1016/j.bmc.2024.117842
Abstrakt: The decline of antibiotics efficacy worldwide has recently reached a critical point urging for the development of new strategies to regain upper hand on multidrug resistant bacterial strains. In this context, the raise of photodynamic therapy (PDT), initially based on organic photosensitizers (PS) and more recently on organometallic PS, offers promising perspectives. Many PS exert their biological effects through the generation of reactive oxygen species (ROS) able to freely diffuse into and to kill surrounding bacteria. Hijacking of the bacterial iron-uptake systems with siderophore-PS conjugates would specifically target pathogens. Here, we report the synthesis of unprecedented conjugates between the siderophore desferrioxamine B (DFOB) and an antibacterial iridium(III) PS. Redox properties of the new conjugates have been determined at excited states and compared to that of an antibacterial iridium PS previously reported by our groups. Tested on nosocomial pathogen Pseudomonas aeruginosa and other bacteria, these conjugates demonstrated significant inhibitory activity when activated with blue LED light. Ir(III) conjugate and iridium free DFOB-2,2'-dipyridylamine ligands were crystallized in complex with FoxA, the outer membrane transporter involved in DFOB uptake in P. aeruginosa and revealed details of the binding mode of these unprecedented conjugates.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: