Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs

Palle J. Pedersen; Mikkel S. Christensen; Tristan Ruysschaert; Lars Linderoth; Thomas L. Andresen; Fredrik Melander; Ole G. Mouritsen; Robert Madsen; Mads H. Clausen

doi:10.1021/jm900091h

Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs

Palle J. Pedersen, Mikkel S. Christensen, Tristan Ruysschaert, Lars Linderoth, Thomas L. Andresen, Fredrik Melander, Ole G. Mouritsen, Robert Madsen, Mads H. Clausen

Section for Plant Glycobiology

62 Citations (Scopus)

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 A₂, 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 A₂, with IC₅₀ values in the 8-36 μM range.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	10
Pages (from-to)	3408-3415
Number of pages	8
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm900091h
Publication status	Published - 28 May 2009

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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 A2, 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 A2, with IC50 values in the 8-36 μM range.",

author = "Pedersen, {Palle J.} and Christensen, {Mikkel S.} and Tristan Ruysschaert and Lars Linderoth and Andresen, {Thomas L.} and Fredrik Melander and Mouritsen, {Ole G.} and Robert Madsen and Clausen, {Mads H.}",

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T1 - Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs

AU - Pedersen, Palle J.

AU - Christensen, Mikkel S.

AU - Ruysschaert, Tristan

AU - Linderoth, Lars

AU - Andresen, Thomas L.

AU - Melander, Fredrik

AU - Mouritsen, Ole G.

AU - Madsen, Robert

AU - Clausen, Mads H.

PY - 2009/5/28

Y1 - 2009/5/28

N2 - 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 A2, 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 A2, with IC50 values in the 8-36 μM range.

AB - 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 A2, 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 A2, with IC50 values in the 8-36 μM range.

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SN - 0022-2623

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EP - 3415

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 10

ER -

Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs

Abstract

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