Design, synthesis and cytotoxic effect of hydroxy- and 3-alkylaminopropoxy-9,10-anthraquinone derivatives

Bioorg Med Chem. 2005 May 16;13(10):3439-45. doi: 10.1016/j.bmc.2005.03.001.

Abstract

In previous paper, we have reported the synthesis and the cytotoxic effect of 1,3-dihydroxy-9,10-anthraquinone derivatives. For further design of more potent compounds, a new series of 1-hydroxy-3-(3-alkylaminopropoxy)-9,10-anthraquinones and 3-(3-alkylaminopropoxy)-9,10-anthraquinones have been synthesized. The cytotoxicity of synthetic compounds were evaluated against human Hep G2, Hep 3B and HT-29 cells. Almost all compounds indicated significant inhibitory activity against Hep G2, Hep 3B and HT-29 cell lines in vitro. Compound 5 exhibited selective cytotoxicity against Hep G2 in a concentration-dependent manner with ED50 value of 1.23 +/- 0.05 microM. Structure-activity analysis revealed that most of the 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthraquinone showed stronger cytotoxic effects than those of 1-hydroxy-3- or 3-(3-alkylaminopropoxy)-9,10-anthraquinones against Hep 3B cell line in vitro. A sub-G1 cell stage and DNA fragmentation in MCF-7 cells were significantly observed after 72 h incubation with selective compound 16. The results show that 16 causes cell death by apoptosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / chemical synthesis*
  • Anthraquinones / chemistry
  • Anthraquinones / pharmacology*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy
  • Carcinoma, Hepatocellular / drug therapy
  • Colonic Neoplasms / drug therapy
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Liver Neoplasms / drug therapy
  • Molecular Structure
  • Tumor Cells, Cultured / drug effects

Substances

  • Anthraquinones
  • Antineoplastic Agents