Organoruthenium Anticancer Agents: Scope and Reactivity

Organometallic compounds have emerged as attractive scaffolds for drug development due to the reactivity that is intrinsic to metal centers and ligand variability leads to several geometries. 2 Cisplatin, PtCl2(NH3)2, and related platinum based drugs have been extensively used as anti-cancer treatments and are highly effective, but suffer from several problems: some cancer lines are resistant to Cisplatin, and these drugs cause severe side effects. Tremendous effort is being expended to develop better platinum drug therapies, but this talk will focus on recent advances in the use of alternative metal centers for organometallic based drugs, primarily those based on ruthenium. Interest in ruthenium based complexes arose from Clarke et al. discovery that the ruthenium(III) ammine RuCl3(NH3)3 showed anticancer activity but was insufficiently soluble to be a competitive anti-cancer agent. Two ruthenium compounds, NAMI-A and KP1019 (Figure 1), were developed from Clarke’s work that have favorable solubility and have displayed anticancer and antitumor activity in clinical trials.