Conformationally restrained ceramide analogues: effects of lipophilic modifications on the antiproliferative activity.
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.
Macchia
Marco
M
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy. mmacchia@farm.unipi.it
Antonello
Michela
M
Bertini
Simone
S
Di Bussolo
Valeria
V
Fogli
Stefano
S
Giovannetti
Elisa
E
Minutolo
Filippo
F
Rapposelli
Simona
S
Danesi
Romano
R
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
D002518:Ceramides; D006131:Growth Inhibitors; D008055:Lipids