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Design, Synthesis and in vitro Anticancer Activity of a Cu(II) Complex of Carminic Acid: A Novel Small Molecule Inhibitor of Human DNA Topoisomerase I and Topoisomerase II
Author(s) -
Das Piyal,
Jain Chetan Kumar,
Roychoudhury Susanta,
Majumder Hemanta Kumar,
Das Saurabh
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201601152
Subject(s) - topoisomerase , anthraquinones , chemistry , dna , superoxide , biochemistry , reactive oxygen species , in vitro , enzyme , stereochemistry , biology , botany
The hydroxy‐9,10‐anthraquinones in anthracyclines form semiquinones and reactive oxygen species (ROS) that help in antitumor activity. ROS generation is cytotoxic to cells but cardiotoxic as well. Carminic acid (CA) with a sugar bound to a hydroxyanthraquinone resembles anthracyclines closely. Role of sugar in anthracyclines was realized from physicochemical parameters of CA that were found to be in between those of anthracyclines and hydroxy‐9,10‐anthraquinones. A Cu(II)complex of CA was prepared and its structure attempted from powder X‐ray diffraction. Studies with DNA revealed unlike CA, the complex did not show decrease in binding constant with increase in the pH of the medium. DNA relaxation assay showed the complex as a dual inhibitor of human DNA topoisomerase I and topoisomerase II stabilizing covalent topoisomerase‐DNA adducts in vitro. Inhibition of growth of ALL‐MOLT‐4 cells was higher for the complex supporting in vitro experiments. An enzyme assay revealed less superoxide formation for the complex suggesting that it might be less cardiotoxic. Decrease in superoxide for the complex does not affect anticancer activity, which was greater than CA.