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The antimalarial activity of Ru–chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces

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Abstract

We have measured water/n-octanol partition coefficients, pK a values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium–π-arene–chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied.

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Acknowledgments

Financial support from the NIH through grants1S06GM 076168-04 and MARC GM08078 is gratefully acknowledged.

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Authors and Affiliations

  1. Chemistry Department, Brooklyn College and The Graduate Center, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY, 11210, USA

    Alberto Martínez, Chandima S. K. Rajapakse, Dalanda Jalloh, Cula Dautriche & Roberto A. Sánchez-Delgado

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  1. Alberto Martínez
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  2. Chandima S. K. Rajapakse
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  3. Dalanda Jalloh
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  4. Cula Dautriche
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  5. Roberto A. Sánchez-Delgado
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Correspondence to Roberto A. Sánchez-Delgado.

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Martínez, A., Rajapakse, C.S.K., Jalloh, D. et al. The antimalarial activity of Ru–chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces. J Biol Inorg Chem 14, 863–871 (2009). https://doi.org/10.1007/s00775-009-0498-4

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  • DOI: https://doi.org/10.1007/s00775-009-0498-4

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