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 journalArticle

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 languageEnglish (US)
Pages (from-to)104-107
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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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