Arene-Ru(II)-Chloroquine Complexes as Potential Antimalarial Agents

Abstract

Malaria is one of the most important parasitic diseases causing over nine million deaths annually. Chloroquine diphosphate (CQDP) was the most widely used drug against malaria but resistant strains of the parasite (Plasmodium falciparum) have emerged throughout the world. Complexation of CQ to metals has been previously shown by us to enhance the activity against resistant strains of the malaria parasite, for instance [RuCl2(CQ)]2. Here we report the synthesis of new Arene-Ru-Chloroquine complexes and their characterization by NMR techniques and DFT calculations. The new complexes are heme aggregation inhibitors, and intercalate in DNA. Preliminary results indicate antimalarial activity and the main mechanism of action is most likely related to the heme aggregation inhibition activity and the lipophilicity of the metal complexes.