Synthesis and structure-activity correlations of the cytotoxic bifunctional 1,4-diamidoanthraquinone derivatives

Hsu Shan Huang, Hui Fen Chiu, An Long Lee, Ching Long Guo, Chun Lung Yuan

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Anthraquinone-based compounds are attractive target for the design of new anticancer drugs. We have previously described a series of 1,5- and 1,4-difunctionalized anthraquinones, which exhibit different spectra of potency, together with human telomerase evaluation. The present study details the preparation of further, distinct series of regioisomeric difunctionalized amidoanthraquinone and examines their in vitro cytotoxicity in C6, Hepa G2, and 2.2.15 cell lines. Two structurally related compounds, mitoxantrone and adriamycin, were tested in parallel as positive controls. The structure-activity relationships indicated amido substitution may lead to a different mechanism of cytotoxicity. Compounds, which have -(CH 2) n- side chains terminating in basic groups such as aminoalkyl-substituted, showed cytotoxic activity in several cell lines. The exact mode of intercalative binding may be dictated by the positional placement of substituent side chains. Implications for amidoanthraquinone cytotoxicity as potential anticancer agents are discussed. In addition, we further delineate the nature of the pharmacophore for this class of compounds, which provides a rational basis for the structure-activity relationships.

Original languageEnglish
Pages (from-to)6163-6170
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number23
DOIs
Publication statusPublished - Dec 1 2004
Externally publishedYes

Fingerprint

Structure-Activity Relationship
Cytotoxicity
Derivatives
Cell Line
Anthraquinones
Mitoxantrone
Telomerase
Cells
Antineoplastic Agents
Doxorubicin
Substitution reactions
Pharmaceutical Preparations
1,4-anthraquinone
In Vitro Techniques

Keywords

  • Amidoanthraquinone
  • Anthraquinone
  • Cytotoxic
  • Mitoxantrone
  • Regioisomeric

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis and structure-activity correlations of the cytotoxic bifunctional 1,4-diamidoanthraquinone derivatives. / Huang, Hsu Shan; Chiu, Hui Fen; Lee, An Long; Guo, Ching Long; Yuan, Chun Lung.

In: Bioorganic and Medicinal Chemistry, Vol. 12, No. 23, 01.12.2004, p. 6163-6170.

Research output: Contribution to journalArticle

Huang, Hsu Shan ; Chiu, Hui Fen ; Lee, An Long ; Guo, Ching Long ; Yuan, Chun Lung. / Synthesis and structure-activity correlations of the cytotoxic bifunctional 1,4-diamidoanthraquinone derivatives. In: Bioorganic and Medicinal Chemistry. 2004 ; Vol. 12, No. 23. pp. 6163-6170.
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