Subcellular Localisation of a Quinoline-Containing Fluorescent Cyclometallated IrIII Complex in Plasmodium falciparum |
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Authors: | Diana R Melis Chiao-Yu Hsiao Dr Jill M Combrinck Prof Lubbe Wiesner Prof Gregory S Smith |
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Affiliation: | 1. Department of Chemistry, University of Cape Town, PD Hahn, Chemistry Mall, Rondebosch, 7701 Cape Town, South Africa;2. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, Observatory, 7925 Cape Town, South Africa |
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Abstract: | A fluorescent analogue of a previously synthesised N,N-chelated IrIII complex was prepared by coordination of the organic ligand to an extrinsic bis(2-phenylpyridine)iridium(III) fluorophore. This cyclometallated IrIII 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. |
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Keywords: | bioorganometallic chemistry cyclometallates fluorescence iridium Plasmodium falciparum |
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