title: Conformationally restrained ceramide analogues: effects of lipophilic modifications on the antiproliferative activity.
abstract: Conformationally restrained analogues of ceramide containing thiouracil or uracil moieties in their polar head, substituted with an ethyl group in their 6-positions, proved to inhibit cell proliferation and induce apoptosis. A series of new thiouracil and uracil analogues of ceramide possessing several 6-alkyl- or 6-arylalkyl-substituents, were synthesized and tested as inhibitors of cell proliferation. The lipophilic substituents introduced in the 6-position were pure alkyls (n-propyl, n-butyl, i-butyl, neo-pentyl), or aryl-alkyls (2-phenylethyl). Although a significant antiproliferative activity was maintained in most compounds synthesized, none of them showed any improvement with respect to their 6-ethyl-substituted counterparts.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy. mmacchia@farm.unipi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.forename: Michela
authors.initials: M
authors.lastname: Antonello
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Valeria
authors.initials: V
authors.lastname: Di Bussolo
authors.forename: Stefano
authors.initials: S
authors.lastname: Fogli
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
mesh_terms: D002236:Carbohydrate Conformation; D002518:Ceramides / Q000737:chemistry* / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002518:Ceramides; D006131:Growth Inhibitors; D008055:Lipids