Synthesis and antitumor evaluation of symmetrical 1,5-diamidoanthraquinone derivatives as compared to their disubstituted homologues

Hsu Shan Huang, Hui F. Chiu, Chi W. Tao, In Been Chen

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A series of symmetrical 1,5-diamidoanthraquinone derivatives with potentially bioreducible groups has been synthesized and their cytostatic activity against the panel of various cancer cell lines in vitro has been studied. Preliminary structure-activity relationships were established. The results indicated that compounds 5 and 18 exhibited significant potent cytotoxicity at 1.24-1.75 μM for Hepa G2 cell line; compounds 5, 16, and 18 exhibited cytotoxicity at 0.14-1.82 μM for 2.2.15 cell line as determined by XTT colorimetric assay. Two structurally related compounds, mitoxantrone and adriamycin, were tested in parallel as positive controls. In addition, it was found that compounds 5 and 18 were a more potent and specific human hepatoma cell line than mitoxantrone and showed comparable activity to adriamycin. Among them, compound 18 was the most potent for 2.2.15 cells. We have demonstrated that the anthraquinone moiety is essential for activity and that less sterically hindered substituents contribute to enhanced in vitro efficacy. Implications for amidoanthraquinone cytotoxicity as potential anticancer agents are discussed. 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)458-464
Number of pages7
JournalChemical and Pharmaceutical Bulletin
Volume54
Issue number4
DOIs
Publication statusPublished - Apr 2006
Externally publishedYes

Fingerprint

Cytotoxicity
Cells
Derivatives
Cell Line
Mitoxantrone
Structure-Activity Relationship
Doxorubicin
Anthraquinones
Cytostatic Agents
Antineoplastic Agents
Hepatocellular Carcinoma
Assays
1,5-diamidoanthraquinone
compound 18
Neoplasms
In Vitro Techniques

Keywords

  • Adriamycin
  • Amidoanthraquinone
  • Cytotoxicity
  • Mitoxantrone
  • Structure-activity relationship
  • XTT colorimetric assay

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

Synthesis and antitumor evaluation of symmetrical 1,5-diamidoanthraquinone derivatives as compared to their disubstituted homologues. / Huang, Hsu Shan; Chiu, Hui F.; Tao, Chi W.; Chen, In Been.

In: Chemical and Pharmaceutical Bulletin, Vol. 54, No. 4, 04.2006, p. 458-464.

Research output: Contribution to journalArticle

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