Synthesis and evaluation of Taxol-folic acid conjugates as targeted antineoplastics

Jae Wook Lee; June Y. Lu; P. S. Low; P. L. Fuchs

doi:10.1016/S0968-0896(02)00019-6

Synthesis and evaluation of Taxol-folic acid conjugates as targeted antineoplastics

Jae Wook Lee, June Y. Lu, P. S. Low, P. L. Fuchs

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

A series of Taxol derivatives tethered at C2′ and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their α-alkoxy and α-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid. One agent (54), further evaluated in animal studies was found to increase the lifespan in mice, but was less effective than Taxol itself.

Original language	English (US)
Pages (from-to)	2397-2414
Number of pages	18
Journal	Bioorganic and Medicinal Chemistry
Volume	10
Issue number	7
DOIs	https://doi.org/10.1016/S0968-0896(02)00019-6
State	Published - 2002

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0968-0896(02)00019-6

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title = "Synthesis and evaluation of Taxol-folic acid conjugates as targeted antineoplastics",

abstract = "A series of Taxol derivatives tethered at C2′ and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their α-alkoxy and α-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid. One agent (54), further evaluated in animal studies was found to increase the lifespan in mice, but was less effective than Taxol itself.",

author = "Lee, {Jae Wook} and Lu, {June Y.} and Low, {P. S.} and Fuchs, {P. L.}",

note = "Funding Information: We thank Endocyte, Inc. for financial support of this research. Dr. Doug Lantrip is thanked for assistance in preparation of this manuscript. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2002",

doi = "10.1016/S0968-0896(02)00019-6",

language = "English (US)",

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journal = "Bioorganic and Medicinal Chemistry",

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T1 - Synthesis and evaluation of Taxol-folic acid conjugates as targeted antineoplastics

AU - Lee, Jae Wook

AU - Lu, June Y.

AU - Low, P. S.

AU - Fuchs, P. L.

N1 - Funding Information: We thank Endocyte, Inc. for financial support of this research. Dr. Doug Lantrip is thanked for assistance in preparation of this manuscript. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2002

Y1 - 2002

N2 - A series of Taxol derivatives tethered at C2′ and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their α-alkoxy and α-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid. One agent (54), further evaluated in animal studies was found to increase the lifespan in mice, but was less effective than Taxol itself.

AB - A series of Taxol derivatives tethered at C2′ and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their α-alkoxy and α-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid. One agent (54), further evaluated in animal studies was found to increase the lifespan in mice, but was less effective than Taxol itself.

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Synthesis and evaluation of Taxol-folic acid conjugates as targeted antineoplastics

Abstract

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