Synthesis and Biophysical Characterization of Chlorambucil Anticancer Ether Lipid Prodrugs

被引：72

作者：

Pedersen, Palle J. ^{[1
]}

Christensen, Mikkel S. ^{[1
]}

Ruysschaert, Tristan ^{[2
]}

Linderoth, Lars ^{[1
]}

Andresen, Thomas L. ^{[3
]}

Melander, Fredrik ^{[4
]}

Mouritsen, Ole G. ^{[2
]}

Madsen, Robert ^{[1
]}

Clausen, Mads H. ^{[1
]}

机构：

[1] Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark

[2] Univ So Denmark, Dept Chem & Phys, MEMPHYS Ctr Biomembrane Phys, DK-5230 Odense M, Denmark

[3] Tech Univ Denmark, Dept Micro & Nanotechnol, DK-4000 Roskilde, Denmark

[4] Tech Univ Denmark, LiPlasome Pharma AS, DK-2800 Lyngby, Denmark

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

PLATELET-ACTIVATING-FACTOR; GROUP-II PHOSPHOLIPASE-A2; IONIZATION MASS-SPECTROMETRY; ASSISTED LASER-DESORPTION; PH-SENSITIVE LIPOSOMES; SECRETORY PHOSPHOLIPASE-A2; MPM; 4-METHOXYBENZYL; IN-VITRO; EXPRESSION; RELEASE;

D O I：

10.1021/jm900091h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：3408 / 3415

页数：8

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