title: Solid-phase synthesis of a combinatorial library of dihydroceramide analogues and its activity in human alveolar epithelial cells.
abstract: Solid-phase synthesis of a small combinatorial library of dihydroceramide analogues as mixtures of erythro and threo diastereomers is described. Some dihydroceramide analogues cause growth arrest and apoptosis in a dose-dependent manner in human alveolar epithelial cells. This activity is likely due to the threo isomers, as evidenced by cellular studies with a pair of diastereomerically pure N-acyldihydrosphingosines. The apoptotic activity reported in this work provides information for the design of new compounds that may provide the basis for the generation of biochemical tools for the study of different pathologies where ceramide and/or dihydroceramide are involved.
authors.affiliation: Research Unit on BioActive Molecules (RUBAM), Departament de Química Orgànica Biològica, Institut d'Investigacions Químiques i Ambientals de Barcelona (IIQAB-C.S.I.C), Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Villorbina
authors.forename: Daniel
authors.initials: D
authors.lastname: Canals
authors.forename: Lydia
authors.initials: L
authors.lastname: Carde
authors.forename: Santiago
authors.initials: S
authors.lastname: Grijalvo
authors.forename: Rosalia
authors.initials: R
authors.lastname: Pascual
authors.forename: Obdulia
authors.initials: O
authors.lastname: Rabal
authors.forename: Jordi
authors.initials: J
authors.lastname: Teixidó
authors.forename: Gemma
authors.initials: G
authors.lastname: Fabriàs
authors.forename: Amadeu
authors.initials: A
authors.lastname: Llebaria
authors.forename: Josefina
authors.initials: J
authors.lastname: Casas
authors.forename: Antonio
authors.initials: A
authors.lastname: Delgado
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D015394:Molecular Structure; D011650:Pulmonary Alveoli / Q000187:drug effects; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D002518:Ceramides; C109343:dihydroceramide