title: Lipocarbazole, an efficient lipid peroxidation inhibitor anchored in the membrane.
abstract: Lipid peroxidation is a major deleterious effect caused by oxidative stress. It is involved in various diseases such as atherosclerosis, rheumatoid arthritis and neurodegenerative diseases. In order to inhibit lipid peroxidation, antioxidants must efficiently scavenge free radicals and penetrate inside biological membranes. Lipocarbazole has recently been shown to be a powerful antioxidant in solution. Here, we show its powerful capacity as lipid peroxidation inhibitor. Its mechanism of action is rationalized based on molecular dynamics simulations on a biomembrane model, quantum calculations and experimental evaluation. The role of the lipocarbazole side chain is particularly highlighted as a critical chemical feature responsible for its antioxidant activity.
authors.affiliation: LCSN-EA1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr. Marcland, 87025 Limoges, France; Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 1192/12, 77146 Olomouc, Czech Republic.
authors.forename: Gabin
authors.initials: G
authors.lastname: Fabre
authors.affiliation: Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Hänchen
authors.affiliation: LCSN-EA1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr. Marcland, 87025 Limoges, France.
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Calliste
authors.affiliation: Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 1192/12, 77146 Olomouc, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Berka
authors.affiliation: Institute for Experimental Molecular Imaging (ExMI), University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Banala
authors.affiliation: Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 1192/12, 77146 Olomouc, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
authors.affiliation: Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
authors.affiliation: Institute for Experimental Molecular Imaging (ExMI), University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; UMR 850 INSERM, Univ. Limoges, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France. Electronic address: patrick.trouillas@unilim.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trouillas
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D013816:Thermodynamics; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002227:Carbazoles; D005227:Fatty Acids; D053835:Unilamellar Liposomes; C013584:lipid peroxidation inhibitor; C041514:carbazole
keywords: Antioxidant; Lipid bilayer membrane; Lipid peroxidation; Molecular dynamics