title: A novel jaspine B-ceramide hybrid modulates sphingolipid metabolism.
abstract: A new sphingolipid hybrid molecule was designed to assemble, within a tail-to-tail double-chain structure, the ceramide hydrophilic moiety and the tetrahydrofuran pharmacophore of jaspine B, a natural product known to interfere with sphingolipid metabolism. This compound was prepared through acylation of sphingosine with a jaspine B derivative bearing a COOH group in the terminal position of the aliphatic backbone. This new hybrid molecule was evaluated for its capacities to affect melanoma cell viability and sphingolipid metabolism. While retaining the cytotoxicity of ceramide itself, this compound was shown to lower the sphingomyelin cellular levels and significantly enhance the production of sphingosine-1-phosphate, thus representing a novel sphingolipid metabolism modulator.
authors.affiliation: INSERM UMR1037, CRCT (Centre de Recherches en Canćerolgie de Toulouse), Oncopole de Toulouse, 2, avenue Hubert Curien, CS 53717, 31037 Toulouse cedex 1.
authors.forename: Virginie
authors.initials: V
authors.lastname: Garcia
authors.affiliation: Lipidomic Core Facility, MetaToul platform, UMR1048 INSERM-Université Paul Sabatier-Toulouse III, CHU Rangueil, BP, FR-84225, Toulouse.
authors.forename: Pauline
authors.initials: P
authors.lastname: Le Faouder
authors.affiliation: Lipidomic Core Facility, MetaToul platform, UMR1048 INSERM-Université Paul Sabatier-Toulouse III, CHU Rangueil, BP, FR-84225, Toulouse.
authors.forename: Aude
authors.initials: A
authors.lastname: Dupuy
authors.affiliation: INSERM UMR1037, CRCT (Centre de Recherches en Canćerolgie de Toulouse), Oncopole de Toulouse, 2, avenue Hubert Curien, CS 53717, 31037 Toulouse cedex 1.
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.affiliation: LSPCMIB, UMR-5068, CNRS, Université de Toulouse, UPS, FR-31062, Toulouse, (phone: +33-561-556299; fax: +33-561-556011). ballereau@chimie.ups-tlse.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ballereau
authors.affiliation: LSPCMIB, UMR-5068, CNRS, Université de Toulouse, UPS, FR-31062, Toulouse, (phone: +33-561-556299; fax: +33-561-556011). genisson@chimie.ups-tlse.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Génisson
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008968:Molecular Conformation; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D002518:Ceramides; D013107:Sphingolipids; C468594:pachastrissamine; D013110:Sphingosine
keywords: Ceramide; Hydrid molecules; Jaspine B; Pachastrissamine; Sphingolipid