Development of Metal Containing Anticancer Drugs Through Investigation of their Topoisomerase Inhibition

This research project focuses on the synthesis and characterization of alternative metal complexes as possible anticancer drugs by assessing their biological activity in terms of topoisomerase inhibition. Cisplatin is one of the most effective anticancer drugs used today however its efficacy is greatly limited by the cancer type. It is speculated that alternative metal centers could have a better effect on combating cancers that are Cisplatin resistant. Several copper (II) containing complexes have been successfully synthesized and published in the Tyler Lab. This work showed that Cu (II) complexes exhibit nuclease activity and they have IC50 values in the micromolar range against Hela and K562 cell lines. Current focus is on the synthesis and characterization of cobalt (III), zinc (II), and nickel (II) analogues for use in similar biological studies, as well as to assess the topoisomerase activity. Topoisomerase is an enzyme that relaxes supercoiled DNA and facilitates DNA replication. Their compounds that exhibit topoisomerase I inhibition may be capable of disrupting the rapid cell replication in cancer tumors and trigger apoptosis. The initial results of these studies will be presented.