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
Pages 122-129
Sayantani Mukherjee, Priya Kalyan Gopal, Santanu Paul and Saurabh Das
DOI: http://dx.doi.org/10.6000/1927-7229.2014.03.03.2
Published: 12 August 2014

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.