| Title | Synthesis and Biophysical Characterization of Chlorambucil Anticancer Ether Lipid Prodrugs. | | Author(s) | Pedersen PJ, Christensen MS, Ruysschaert T, Linderoth L, Andresen TL, Melander F, Mouritsen OG, Madsen R, Clausen MH | | Institution | Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, DK-2800 Kgs. Lyngby, Denmark, Department of Physics and Chemistry, MEMPHYSCenter for Biomembrane Physics, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark, Department of Micro- and Nanotechnology, Technical University of Denmark, DK-4000 Roskilde, Denmark, and LiPlasome Pharma A/S, Technical University of Denmark, Kemitorvet, Building 207, DK-2800 Kgs. Lyngby, Denmark. | | Source | J Med Chem 2009 Apr 29. | | 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 muM range. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19402667 |
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