Modular Design of Mitochondrion-Targeted Iron Chelators Allows Highly Selective Antiparasitic Activity against Trypanosomes and Apicomplexan Parasites
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F25%3A00086115" target="_blank" >RIV/00023001:_____/25:00086115 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00548?ref=article_openPDF" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00548?ref=article_openPDF</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsinfecdis.5c00548" target="_blank" >10.1021/acsinfecdis.5c00548</a>
Alternative languages
Result language
angličtina
Original language name
Modular Design of Mitochondrion-Targeted Iron Chelators Allows Highly Selective Antiparasitic Activity against Trypanosomes and Apicomplexan Parasites
Original language description
Parasitic protozoa exhibit a high demand for iron, with mitochondrial iron metabolism representing a vulnerable target for chemotherapeutic intervention. We recently demonstrated that mitochondrial targeting of the iron chelator deferoxamine (DFO) via triphenylphosphonium (TPP) conjugation enhances its antiparasitic efficacy. To expand upon this strategy, mitochondrially targeted derivatives of DFO and deferasirox (DFX) were synthesized and evaluated for their activity against important human parasites. The DFX derivative mitoDFX was effective against Trypanosoma spp. and Toxoplasma gondii with remarkable selectivity. The fact that mitoDFX is a promising anticancer agent, which is likely safe to use in the context of human health, highlights the potential for drug repurposing in parasitology. Structure-activity relationship (SAR) studies and iron distribution analyses in trypanosomes revealed that mitochondrial targeting of the compounds, rather than iron chelation per se, is the main driver of the antiparasitic effects, underscoring the critical role of phosphonium salts in bioactivity.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30303 - Infectious Diseases
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS infectious diseases
ISSN
2373-8227
e-ISSN
—
Volume of the periodical
12
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
119-127
UT code for WoS article
001644783300001
EID of the result in the Scopus database
2-s2.0-105026879937