title: Synthesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid bilayers and monolayers.
abstract: Cytarabine (1-β-D-arabinofuranosylcytosine, Ara-C), a pyrimidine nucleoside analogue, is an attractive therapeutic agent for the treatment of both acute and chronic myeloblastic leukemias. 1,1',2-tris-nor-Squalene acid (squaleneCOOH) has been conjugated to cytarabine with the formation of the squalenoyl-cytarabine prodrug, in order to improve the drug lipophilicity and, consequently, the affinity towards the environment of biological membranes, as well as of lipophilic carriers. The interaction of cytarabine and its prodrug with dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles and monolayers has been studied by the differential scanning calorimetry and the Langmuir-Blodgett techniques. The interaction has been evaluated considering the effect of the compounds on the DMPC MLV and monolayers behaviour. The aim was to have information on the interaction of the drug and the prodrug with the biological membranes and on the possibility to use liposomes as carriers for the prodrug. The results showed an improved affinity of the prodrug with MLV and monolayers with respect to the free drug.
authors.affiliation: Dipartimento di Scienze Chimiche, Viale Andrea Doria 6, 95125 Catania, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sarpietro
authors.forename: Sara
authors.initials: S
authors.lastname: Ottimo
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Giuffrida
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceruti
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D013185:Squalene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008051:Lipid Bilayers; D008081:Liposomes; D011355:Prodrugs; C558489:n-squalenoyl-cytarabine; D003561:Cytarabine; D013185:Squalene; D004134:Dimyristoylphosphatidylcholine