title: Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs.
abstract: The synthesis and biophysical characterization of four prodrug ether phospholipid conjugates are described. The lipids are prepared from the anticancer drug chlorambucil and have C16 and C18 ether chains with phosphatidylcholine or phosphatidylglycerol headgroups. All four prodrugs have the ability to form unilamellar liposomes (86-125 nm) and are hydrolyzed by phospholipase A(2), resulting in chlorambucil release. Liposomal formulations of prodrug lipids displayed cytotoxicity toward HT-29, MT-3, and ES-2 cancer cell lines in the presence of phospholipase A(2), with IC(50) values in the 8-36 microM range.
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Palle J
authors.initials: PJ
authors.lastname: Pedersen
authors.forename: Mikkel S
authors.initials: MS
authors.lastname: Christensen
authors.forename: Tristan
authors.initials: T
authors.lastname: Ruysschaert
authors.forename: Lars
authors.initials: L
authors.lastname: Linderoth
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andresen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Melander
authors.forename: Ole G
authors.initials: OG
authors.lastname: Mouritsen
authors.forename: Robert
authors.initials: R
authors.lastname: Madsen
authors.forename: Mads H
authors.initials: MH
authors.lastname: Clausen
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D008081:Liposomes; D054467:Phospholipases A2 / Q000378:metabolism; D010742:Phospholipid Ethers / Q000138:chemical synthesis; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008081:Liposomes; D010742:Phospholipid Ethers; D011355:Prodrugs; D002699:Chlorambucil; D054467:Phospholipases A2