Acetylation of 1,2,5,8-tetrahydroxy-9,10-anthraquinone Improves Binding to DNA and Shows Enhanced Superoxide Formation that Explains Better Cytotoxicity on JURKAT T Lymphocyte Cells

Authors

  • Sayantani Mukherjee Department of Chemistry, Jadavpur University, Kolkata – 700 032, India
  • Priya Kalyan Gopal Laboratory of Experimental Immunology, Department of Botany, Gurudas College, Kolkata 700 054, India
  • Santanu Paul Laboratory of Experimental Immunology, Department of Botany, Gurudas College, Kolkata 700 054, India
  • Saurabh Das Department of Chemistry, Jadavpur University, Kolkata – 700 032, India

DOI:

https://doi.org/10.6000/1927-7229.2014.03.03.2

Keywords:

Acetylated1,2,5,8-tetrahydroxy-9,10-anthraquinone (THAQ-ace), anthracycline, calf thymus DNA, superoxide, JURKAT T lymphocyte cells.

Abstract

 Background: Hydroxy-9,10-anthraquinones form the core unit of anthracycline anticancer drugs and are close structural analogues to these drugs. Although they show close resemblance to anthracyclines in physicochemical characteristics and electrochemical behavior their biophysical interactions are somewhat weaker than anthracyclines which is a disadvantage. One reason is the formation of anionic species by hydroxy-9,10-anthraquinones. Hence if formation of anionic species is prevented there could be a possibility hydroxy-9,10-anthraquinones would bind DNA better.

Procedure: For this 1, 2, 5, 8-tetrahydroxy-9,10-anthraquinone (THAQ) was acetylated to obtain a tetra-acetylated derivative (THAQ-ace) whose interaction with calf thymus DNA was studied using UV-Vis spectroscopy at different pH.

Results: Binding constant values for THAQ-ace (~105) were higher than THAQ at different pH. Increase in binding constant was attributed to anionic species not formed for THAQ-ace at physiological pH. Hence, unlike THAQ, binding constant values for THAQ-ace interacting with calf thymus DNA did not show variation with pH. In fact, it remained more or less constant. Increase in size of the acetylated form (THAQ-ace) compared to THAQ had a negative influence on binding. THAQ-ace showed enhanced superoxide formation. Both DNA binding and superoxide formation were responsible for a significant improvement in anticancer activity for THAQ-ace compared to THAQ on Jurkat T lymphocyte cells.

Conclusion: Binding constant values for THAQ-ace binding to DNA were close to that reported for some standard anthracyclines. Hence, suitable modification of the less costly hydroxy-9,10-anthraquinones could provide alternatives to anthracyclines in cancer chemotherapy.

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Published

2014-08-03

How to Cite

Sayantani Mukherjee, Priya Kalyan Gopal, Santanu Paul, & Saurabh Das. (2014). Acetylation of 1,2,5,8-tetrahydroxy-9,10-anthraquinone Improves Binding to DNA and Shows Enhanced Superoxide Formation that Explains Better Cytotoxicity on JURKAT T Lymphocyte Cells. Journal of Analytical Oncology, 3(3),  122–129. https://doi.org/10.6000/1927-7229.2014.03.03.2

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