Mode of action of iron (III) chelators as antimalarials: I. Membrane permeation properties and cytotoxic activity.

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

Blood

journal_title

Blood

authors

Lytton SD,Mester B,Dayan I,Glickstein H,Libman J,Shanzer A,Cabantchik ZI

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

214-21

issue

1

eissn

0006-4971

issn

1528-0020

journal_volume

81

pub_type

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