NAPHTHOQUINONE ANTIMALARIALS

XIX. Antirespiratory Study of Protein Binding

¹ Chemical Laboratory, Harvard University

1. Satisfactory methods have been found for the accurate assay of naphthoquinone pigment in plasma samples and for the preparation of plasma extracts (alcohol) suitable for respiratory study.

2. Difficulties encountered in ether extraction are attributable to the binding of naphthoquinone to protein. Exploratory dialysis and solubility experiments show that the compounds are bound particularly to albumin; a typical naphthoquinone-albumin complex has an apparent acidity about 1.6 pK units lower than that of the free naphthoquinone. The drug-binding power of three plasmas, as judged by dialysis experiments, is in the order: human monkey duck.

3. Little if any naphthoquinone diffuses from the plasma into the red blood cells.

4. Protein antagonism to drug action as measured by the depression of the inhibitory action of naphthoquinones on the respiration of parasitized erythrocytes, decreases in the order: human serum chicken serum duck serum; the difference in protein antagonism between chicken and duck plasma may account for marked differences noted in the antimalarial potency of naphthoquinones in these species.

5. Susceptibility to human-protein antagonism varies markedly from compound to compound, and the characterization of naphthoquinones with respect to this factor affords a further criterion for the laboratory evaluation of their promise in therapy.