Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 10, Pages 3408-3415Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm900091h
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Funding
- Danish Council for Strategic Research (NABIIT Program)
- Danish National Research Foundation.
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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 IC50 values in the 8-36 mu M range.
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