Utilizing coordination chemistry through formation of a CuII-quinalizarin complex to manipulate cell biology: An in vitro, in silico approach

Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A CuII complex was prepared and characterized by elemental analysis, UV-Vis & IR spectroscopy, mass spectrometry, EPR and DFT. The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. While the first two attributes of complex formation lead to increased efficacy, decrease in semiquinone generation could results in a compromise with efficacy. Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. The complex unlike quinalizarin, does not catalyze flow of electrons from NADH to O2 to the extent known for quinalizarin. Hence, decrease in semiquinone or superoxide radical anion could make modified quinalizarin [as CuII complex] less efficient in free radical pathway. However, it would be less cardiotoxic and that would be advantageous to qualify it as a better anticancer agent. Although binding to calf thymus DNA was comparable to quinalizarin, it was weaker than anthracyclines. Low cost of quinalizarin could justify consideration as a substitute for anthracyclines but the study revealed IC50 of quinalizarin/CuII-quinalizarin was much higher than anthracyclines or their complexes. Even then, there is a possibility that CuII-quinalizarin could be an improved and less costly form of quinalizarin as anticancer agent. Synopsis: A CuII complex of quinalizarin was prepared with the intention of increasing cellular uptake, study binding with DNA, modulate formation of semiquinone and check for inhibition of human DNA topoisomerase I and II to correlate observed anticancer activity. Low cost of quinalizarin justifies its consideration as a substitute for anthracyclines. [Display omitted] •Quinalizarin (THAQ), an analogue of anthracyclines, is active pharmacologically.•Complex formation modulates generation of free radicals that affect its mechanism of action.•The complex is an efficient inhibitor of topoisomerase enzymes, crucial for drug action.•Interaction of [CuII(THAQ)2(H2O)2] with topoisomerase was realized by molecular docking.•THAQ, the acetylated form, shows more efficacy on ALL MOLT 4