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Conformationally restrained ceramide analogues: effects of lipophilic modifications on the antiproliferative activity
Authors:Macchia Marco  Antonello Michela  Bertini Simone  Di Bussolo Valeria  Fogli Stefano  Giovannetti Elisa  Minutolo Filippo  Rapposelli Simona  Danesi Romano
Institution:Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy. mmacchia@farm.unipi.it
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.
Keywords:Apoptosis  Ceramide analogues  Thiouracil  Uracil  Lipophilicity
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