Subcellular Localisation of a Quinoline-Containing Fluorescent Cyclometallated IrIII Complex in Plasmodium falciparum

A fluorescent analogue of a previously synthesised N,N-chelated Ir-III complex was prepared by coordination of the organic ligand to an extrinsic bis(2-phenylpyridine)iridium(III) fluorophore. This cyclometallated Ir-III complex in itself displays good, micromolar activity against the chloroquine-sensitive NF54 strain of Plasmodium falciparum. Live-cell confocal microscopy found negligible localisation of the fluorescent complex within the digestive vacuole of the parasite. This eliminated the haem detoxification pathway as a potential mechanism of action. Similarly, no localisation of the complex within the parasitic nucleus was found, thus suggesting that this complex probably does not interfere with the DNA replication process. A substantial saturation of fluorescence from the complex was found near phospholipid structures such as the plasma and nuclear membranes but not in neutral lipid bodies. This indicates that an association with these membranes, or organelles such as the endoplasmic reticulum or branched mitochondrion, could be essential to the efficacies of these types of antimalarial compounds.

Automated summary

The fluorescent analogue of a previously synthesised N,N-chelated Ir-III complex displayed micromolar activity against the chloroquine-sensitive NF54 strain of Plasmodium falciparum, without interfering with DNA replication. The fluorescence saturation near phospholipid structures suggests an essential association with membranes or organelles for the efficacy of these antimalarial compounds.