# REVERSED SIDEROPHORES AS ANTI-MALARIAL AGENTS

> **NIH NIH R01** · HEBREW UNIVERSITY OF JERUSALEM · 1993 · $169,753

## Abstract

Global spread of malaria and resurgence of drug resistant parasites in
various regions of the world has created an urgent need for novel
chemotherapies. The goal of malaria chemotherapy in general, and of this
proposal in particular, is two fold: to selectively affect infected cells
with minimal damage to the host organism and to eliminate parasites,
including those of highest drug resistance nature. The means by which this
goal is meant to be accomplished comprises synthesis and evaluation of
novel agents as well as assessment of their mode of action. Two concepts
developed in the participating laboratories provide the basis of the
proposal: a. selective targeting of drugs based on differential permeation
(the ostensible differences in permeation properties of P. falciparum
infected red blood cells previously characterized in biophysical terms,
serve here as the main route for drug access into infected cells and b.
drug design based on a biomimetic approach of iron(III) chelation and
modular building for optimizing drug properties (biochemical and
pharmacological).  The novel drugs are iron carriers based on both
ferrichrome and ferrioxamine which are synthesized with requisite
hydrophobicity and/or dimensions so as to exert differential deprivation
of intracellular iron (III) pools. Novel agents tested for their ability
(dose and speed of action) to arrest in vivo parasite growth including
drug resistant P. falciparum strains and to arrest in vivo growth in model
rodent animals,provided ample support for the feasibility of all the
proposed approaches. The additional rationale on which the work lies, is
that unlike cells of the mammalian organism which can demonstrably
withstand temporary iron deprivation (chelator treatment) regimes and can
fully recover from them, intracellular parasites apparently can not.
Support for that hypothesis encompasses: modular drug design of traceable
(fluorescent and radioactive) forms of chelators with variable size and
hydrophobicities and their application for time-resolved tracing of drug
permeation into parasitized cells (at various developmental stages), for
compartmental drug distribution, for identification of putative
biochemical targets (activities associated with iron containing enzymes
and parasite-derived endogenous iron(III) shuttles/ carriers) and for
assessment of iron acquisition paths in parasitized cells.

The project is meant to provide both scientific and applicative grounds
for alternative or supplemental chemotherapy for a disease whose
eradication is still considered a major health target for mankind.

## Key facts

- **NIH application ID:** 3129959
- **Project number:** 2R01AI020342-07A1
- **Recipient organization:** HEBREW UNIVERSITY OF JERUSALEM
- **SAM.gov UEI:** HJDLWK8DNDL7
- **Principal Investigator:** ZVI IOAV CABANTCHIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $169,753
- **Award type:** 2
- **Project period:** 1983-09-01 → 1996-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129959

## Citation

> US National Institutes of Health, RePORTER application 3129959, REVERSED SIDEROPHORES AS ANTI-MALARIAL AGENTS (2R01AI020342-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129959. Licensed CC0.

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