A CobaltII/CobaltIII complex of alizarin that was analyzed from the stand point of binding with DNA, for ROS generation and anticancer drug prospecting was identified as an analogue of anthracyclines

Abstract

A coordination compound of CoII with alizarin was prepared to see if it resembles various activities that are reported for anthracyclines as anticancer agents. Alizarin, which has a comparatively simpler structure than anthracyclines, contain the same hydroxy-9,10-anthraquinone as found in anthracyclines. Hence, if tried in cancer chemotherapy, it is expected to show some advantages related to cost and for all those reasons that become applicable in using a relatively simpler compound. However, to be acceptable, it must show comparable efficacy as known for anthracyclines. Like anthracyclines, alizarin forms the semiquinone radical anion that generates superoxide radical anion, responsible for cardiotoxicity. Complex formation decreases generation of superoxide, that was verified by an enzyme assay that might help to decrease toxic side effects. Although hydroxy-9,10-anthraquinones (here alizarin), resemble anthracyclines, biophysical and/or biochemical interactions of the former at the cellular level are less efficient than the latter. Besides, under physiological conditions alizarin is anionic. Hence, increase in pH affects DNA binding adversely. The prepared complex, which is anionic, when it has CoII and neutral when CoIII, binds DNA better than alizarin under varying conditions of ionic strength and pH. Since reactive oxygen species are present in cells, there is a high probability that the CoII complex could either completely or partially convert to CoIII. The CoIII species would then manifest in several biological responses affecting the growth of cells. Experiments pertaining to ROS were performed on three human cell lines (SIHA, HepG2, WI 38) that suggest a shift in mechanism for the complex/complexes from that known for anthracyclines or hydroxy-9,10-anthraquinones. An expected loss in efficacy due to decreased semiquinone formation is compensated by the CoII/CoIII couple owing to the metal ion being present in two oxidation states in cellular medium thus promoting cytotoxicity. The CoII/CoIII complex tried on cells reveal several attributes that enable it/them to overcome some of the shortcomings of alizarin to become comparable to anthracyclines.