A comparative study on the interaction with calf thymus DNA of a Ni(II) complex of the anticancer drug adriamycin and a Ni(II) complex of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate

摘要

The anthracycline drug adriamycin and its metal complexes are efficient in treating several forms of human cancers with recognized antineoplastic activity attributed to strong interactions with DNA within the target cells. The hydroxy-9,10-anthraquinone unit present in the molecule controls and regulates drug action. Metal ions when linked to adriamycin help to reduce the generation of radicals responsible for toxic side effects. A complex of adriamycin with Ni(II) was prepared and its physicochemical characteristics and DNA-binding ability were compared to a Ni(II) complex of sodium-l,4-dihydroxy-9,10-anthraquinone-2-sulphonate (NaLH_2), an analog of adriamycin. Interactions with calf thymus DNA of both complexes were studied by UV-Vis and fluorescence spectroscopy. Binding parameters determined for both complexes agree with each other. Binding of the Ni(II)-adriamycin complex to DNA was five to eight times stronger than for the Ni(II) complex of the hydroxy-9,10-anthraquinone analog, Na_2[Ni(NaLH)_2Cl_2] ·2H_2O, i.e., Ni(NaLH)_2. The difference in binding was attributed to the presence of sugar units in adriamycin and to its absence in NaLH_2. Although the Ni(II) complex of the hydroxy-9,10-anthraquinone analog of adriamycin [Ni(NaLH)_2] was slightly weaker in binding DNA than the drug and its Ni(II) complex, a much lower cost of the former justifies its consideration as a substitute for the anthracycline drugs that are now in use.