Abstract:
:We have designed two subfamilies of lipophilic iron (III) chelators previously termed reversed siderophores (RSFs). The agents display physicochemical properties that favor extraction of iron beyond membrane barriers of Plasmodium falciparum-infected red blood cells. We studied the in vitro antimalarial potency of RSFs and their relationship to the membrane permeation properties of these agents. The mode of RSF action involves: (1) fast access to intracellular compartments of parasitized cells; (2) selective and high-affinity chelation of iron (III) from parasitized cells; (3) fast exit from cells after iron (III) complexation; and (4) exertion of cell damage on parasites exposed for 3 to 5 hours to drugs, irrespective of the stage of parasite development. These results suggest that on reaching a critical intraerythrocyte target, RSFs induce an iron deficit that parasites in general, and rings in particular, have limited capacity to restore.
journal_name
Bloodjournal_title
Bloodauthors
Lytton SD,Mester B,Dayan I,Glickstein H,Libman J,Shanzer A,Cabantchik ZIsubject
Has Abstractpub_date
1993-01-01 00:00:00pages
214-21issue
1eissn
0006-4971issn
1528-0020journal_volume
81pub_type
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