Kinetics of quinine-deuterohemin binding

Interaction of Iron(III)-5,10,15,20-Tetrakis (4-Sulfonatophenyl) Porphyrin with Chloroquine, Quinine and Quinidine

“…The pH values were measured with a glass electrode, which was soaked and kept in aqueous solution of KCl (3 M) and was calibrated with aqueous standard buffers. A series of titration solutions at pH 7.40 were prepared as previously described [4] [28] in which the concentrations of FeTPPS μ-oxo dimer (D), TRIS and NaNO 3 were held constant, at 5 × 10 −6 M, 0.01 M and 0 or 0.1 M, respectively, while the concentrations of the antimalarial ligand (L) were varied from 0 to 1.5 M.…”

“…Iron(III)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (FeTPPS), widely used in medicine to attenuate neurological damages, but also to treat the retinopathy of prematurity and for reanimation [8], is a synthetic derivative of the natural Iron(III)-protoporphyrin IX (FePPIX) (Figure 1). FePPIX has been suggested as drug target of quinoline-based antimalarials [4] [9] [10] [11] [12] [13]. FePPIX is the oxidized form of heme released by the malarial parasite during the blood stage.…”

“…The parasite digests hemoglobin in infected erythrocytes to recuperate the amino acids it needs. Detoxification of free heme into the acidic digestive vacuole is achieved by the formation of a polymer well known as hemozoin (β-hematin) or malarial pigment [4] [14]. The interaction of quinoline antimalarial with FePPIX plays the important role of bringing back the porphyrin into solution in order to block FePPIX unities, and to prevent the formation of hemozoin.…”

“…The interaction of quinoline antimalarial with FePPIX plays the important role of bringing back the porphyrin into solution in order to block FePPIX unities, and to prevent the formation of hemozoin. The binding of FePPIX and its derivate Iron(III)-deuteroporphyrin IX (FeDPIX) to quinoline-based antimalarials Chloroquine, Quinine and Quinidine (Figure 2) have been demonstrated in vitro using mixtures of water with ethylene glycol, propylene glycol and DMSO [4] [11] [12] [15] [16] [17] [18]. It has been shown that the interaction depends on steric, stereochemical and electrostatic effects.…”

“…However, quantitative studies of the interaction of the iron (III) porphyrin FePPIX in pure aqueous solution, the physiological medium, are hampered by the tendency of FePPIX to form aggregates considerably larger than dimers. In weakly acid and neutral solutions of FePPIX, a stable state cannot be achieved probably due to colloidal precipitation leading to artefacts in quantitative investigations [4] …”