Bioorg Med Chem 2007 Jan 17;15(1):50-62. Epub 2006 Oct 17.
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.
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.