The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

Chengzao Sun; Simon E. Aspland; Carlo Ballatore; Rosario Castillo; Amos B. Smith; Angelo J. Castellino

doi:10.1016/j.bmcl.2005.09.046

The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

Chengzao Sun, Simon E. Aspland, Carlo Ballatore, Rosario Castillo, Amos B. Smith, Angelo J. Castellino

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

8 Scopus citations

Abstract

The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3′-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3′-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven DOX-amino acid conjugates were prepared, each displaying similar inhibitory activity as the parent drug.

Original language	English (US)
Pages (from-to)	104-107
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2005.09.046
State	Published - Jan 1 2006
Externally published	Yes

Keywords

Anthracycline
Conjugate
Doxorubicin
Maleimide
Topoisomerase II

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2005.09.046

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AU - Aspland, Simon E.

AU - Ballatore, Carlo

AU - Castillo, Rosario

AU - Smith, Amos B.

AU - Castellino, Angelo J.

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AB - The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3′-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3′-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven DOX-amino acid conjugates were prepared, each displaying similar inhibitory activity as the parent drug.

KW - Anthracycline

KW - Conjugate

KW - Doxorubicin

KW - Maleimide

KW - Topoisomerase II

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The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

Abstract

Keywords

ASJC Scopus subject areas

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