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Dalton Trans. 2012 Mar 7;41(9):2764-73. doi: 10.1039/c2dt12083f. Epub 2012 Jan 17.

Ruthenium(II) arene complexes with chelating chloroquine analogue ligands: synthesis, characterization and in vitro antimalarial activity.

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  • 1Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, Lund, Sweden.

Abstract

Three new ruthenium complexes with bidentate chloroquine analogue ligands, [Ru(η(6)-cym)(L(1))Cl]Cl (1, cym = p-cymene, L(1) = N-(2-((pyridin-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine), [Ru(η(6)-cym)(L(2))Cl]Cl (2, L(2) = N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) and [Ru(η(6)-cym)(L(3))Cl] (3, L(3) = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine) have been synthesized and characterized. In addition, the X-ray crystal structure of 2 is reported. The antimalarial activity of complexes 1-3 and ligands L(1), L(2) and L(3), as well as the compound N-(2-(bis((pyridin-2-yl)methyl)amino)ethyl)-7-chloroquinolin-4-amine (L(4)), against chloroquine sensitive and chloroquine resistant Plasmodium falciparum malaria strains was evaluated. While 1 and 2 are less active than the corresponding ligands, 3 exhibits high antimalarial activity. The chloroquine analogue L(2) also shows good activity against both the chloroquine sensitive and the chloroquine resistant strains. Heme aggregation inhibition activity (HAIA) at an aqueous buffer/n-octanol interface (HAIR(50)) and lipophilicity (D, as measured by water/n-octanol distribution coefficients) have been measured for all ligands and metal complexes. A direct correlation between the D and HAIR(50) properties cannot be made because of the relative structural diversity of the complexes, but it may be noted that these properties are enhanced upon complexation of the inactive ligand L(3) to ruthenium, to give a metal complex (3) with promising antimalarial activity.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00563914 NCT00988507.

PMID:
22249579
PMCID:
PMC3303165
DOI:
10.1039/c2dt12083f
[PubMed - indexed for MEDLINE]
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