Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs

Wolf Wrasidlo; Ulrike Schröder; Kathrin Bernt; Nicole Hübener; Doron Shabat; Gerhard Gaedicke; Holger Lode

doi:10.1016/S0960-894X(01)00801-0

Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs

Wolf Wrasidlo^*
, Ulrike Schröder
, Kathrin Bernt
, Nicole Hübener
, Doron Shabat
, Gerhard Gaedicke
, Holger Lode

^*Corresponding author for this work

School of Chemistry

Humboldt University of Berlin

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

24 Scopus citations

Abstract

Two 4′-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude.

Original language	English
Pages (from-to)	557-560
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/S0960-894X(01)00801-0
State	Published - 25 Feb 2002

Funding

Funders	Funder number
Deutsche Forschungsgemeinschaft	Lo 635/2-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/S0960-894X(01)00801-0

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title = "Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs",

abstract = "Two 4′-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude.",

author = "Wolf Wrasidlo and Ulrike Schr{\"o}der and Kathrin Bernt and Nicole H{\"u}bener and Doron Shabat and Gerhard Gaedicke and Holger Lode",

note = "Funding Information: We are very grateful to Dr. Muegge, Chemistry Department, for the determination of the NMR spectra and Dr. Janek, Biochemistry Department, for the mass spectra. This work was supported by the DFG, Emmy-Noether Program Lo 635/2-2. ",

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AU - Wrasidlo, Wolf

AU - Schröder, Ulrike

AU - Bernt, Kathrin

AU - Hübener, Nicole

AU - Shabat, Doron

AU - Gaedicke, Gerhard

AU - Lode, Holger

N1 - Funding Information: We are very grateful to Dr. Muegge, Chemistry Department, for the determination of the NMR spectra and Dr. Janek, Biochemistry Department, for the mass spectra. This work was supported by the DFG, Emmy-Noether Program Lo 635/2-2.

PY - 2002/2/25

Y1 - 2002/2/25

N2 - Two 4′-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude.

AB - Two 4′-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude.

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SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs

Abstract

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UN SDGs

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