Arene-Ru-chloroquine complexes as potential antimalarial or antitumor agents: DNA binding and heme aggregation inhibition properties

Abstract

The success of cisplatin has stimulated the area of inorganic medicinal chemistry. Ruthenium complexes are being developed for applications in several diseases including cancer and malaria. Chloroquine diphosphate (CQDP) is a common antimalarial treatment, but widespread resistance dramatically limits its use. We have previously shown that complexation of CQ to metals enhances the activity against resistant strains of Plasmodium falciparum, e.g. in [RuCl2(CQ)]2. CQDP has also increases the efficacy of standard anticancer treatments through a lysosomotropic effect, which raises an interesting possibility for cisplatin-resistant tumors. We synthesized a series of new Ru-chloroquine complexes including (arene)RuCl2(CQ), [(arene)Ru(CQ)][PF6]2 (arene = p-cymene or benzene) and Cp*RuCl(CQ) and characterized them by 1D/2D NMR and other methods. We have studied the interaction of the new complexes with DNA by several techniques and their potential as heme aggregation inhibitors. These compounds are promising candidates as dual-target antimalarial agents and possibly also as antitumor agents.