In vivo antimalarial action of a lipophilic iron (III) chelator: Suppression of plasmodium vinckei infection by reversed siderophore

We assessed in vivo antimalarial action of a lipophilic iron (III) chelator belonging to a new synthetic family of biomimetic siderophores previously termed reversed siderophores (RSFs). The family member, RSF ileu_m2, was chosen for its high membrane permeability and fast irreversible inhibition of human malaria parasite growth in vitro. [Shanzer A, et al., Proc Natl Acad Sci USA 88:6585, 1991 and Lytton SD, et al., Blood 81:214, 1993]. The lipophilic drug was administered to Swiss mice by subcutaneous route in fractionated coconut oil at a dosage of 0.37 g/kg every 8 hr with no adverse reactions observed. After 3–4 injections demonstrable suppression of Plasmodium vinckei petteri infection was observed and an additional 3–4 injections resulted in 2–3‐fold lower parasitemia with prolonged survival time over sham‐injected control mice.