Modular Design of Mitochondrion-Targeted Iron Chelators Allows Highly Selective Antiparasitic Activity against Trypanosomes and Apicomplexan Parasites

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Modular Design of Mitochondrion-Targeted Iron Chelators Allows Highly Selective Antiparasitic Activity against Trypanosomes and Apicomplexan Parasites

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Modular Design of Mitochondrion-Targeted Iron Chelators Allows Highly Selective Antiparasitic Activity against Trypanosomes and Apicomplexan Parasites

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30303 - Infectious Diseases

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS infectious diseases

ISSN

2373-8227

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

119-127

Kód UT WoS článku

001644783300001

EID výsledku v databázi Scopus

2-s2.0-105026879937