Reversed siderophores as antimalarial agents. II. Selective scavenging of Fe(III) from parasitized erythrocytes by a fluorescent derivative of desferal

We introduce here a fluorescent derivative of desferrioxamine B (DFO) that retains the high affinity of the parent compound and displays a powerful inhibition of intraerythrocytic Plasmodium falciparum growth. NBD-DFO was synthesized by coupling 7-Nitrobenz-2-oxa-1,3-diazole (NBD) to the terminal amino group of DFO. The NBD group at this position renders the DFO molecule more lipophilic and imparts to it fluorescent properties. The novel NBD-DFO probe displays a unique combination of chemical and biological properties, such as 1) improved and selective permeation properties across membranes of P. falciparum-infected erythrocytes, 2) improved efficacy as an inhibitor of intraerythrocytic P. falciparum growth (including multidrug-resistant strains), 3) demonstrable Fe³⁺ scavenging within parasitized red cells, and 4) usefulness as a sensitive and versatile analytical tool for quantitative assessment of Fe³⁺ and for following iron-scavenging processes, because the fluorescence of NBD-DFO is demonstrably quenched upon complexation with Fe³⁺.