title: 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.
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-pi-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.
authors.affiliation: Chemistry Department, Brooklyn College, The City University of New York, Brooklyn, NY 11210, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez
authors.forename: Chandima S K
authors.initials: CS
authors.lastname: Rajapakse
authors.forename: Dalanda
authors.initials: D
authors.lastname: Jalloh
authors.forename: Cula
authors.initials: C
authors.lastname: Dautriche
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Sánchez-Delgado