Topoisomerase II poisoning by indazole and imidazole complexes of ruthenium

Trans-imidazolium (bis imidazole) tetrachloro ruthenate (RuIm) and trans-in dazolium (bis indazole) tetrachloro ruthenate (RuInd) are ruthenium coordin ation complexes, which were first synthesized and exploited for their antic ancer activity. Those molecules constitute two of the few most effective an ticancer ruthenium compounds. The clinical use of these compounds however w as hindered due to toxic side effects on the human body. Our present study on topoisomerase II poisoning by these compounds shows that they effectivel y poison the activity of topoisomerase II by forming a ternary cleavage com plex of DNA, drug and topoisomerase II. The thymidine incorporation assays show that the inhibition of cancer cell proliferation correlates with topoi somerase II poisoning. The present study on topoisomerase II poisoning by t hese two compounds opens a new avenue for renewing further research on thes e compounds. This is because they could be effective lead candidates for th e development of more potent and less toxic ruthenium containing topoisomer ase II poisons. Specificity of action on this molecular target may reduce t he toxic effects of these ruthenium-containing molecules and thus improve t heir therapeutic index.