Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach

In the search for a more effective chemotherapy for the treatment of Chagas’ disease, caused by Trypanosoma cruzi parasite, the use of gold compounds may be a promising approach. In this work, four gold(I) compounds [AuCl(HL)], (HL = bioactive 5-nitrofuryl containing thiosemicarbazones) were studied...

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Published in:Inorganics 2024-05, Vol.12 (5), p.133
Main Authors: Órdenes-Rojas, Javiera, Risco, Paola, Ortega-Campos, José, Barriga-González, Germán, Liempi, Ana, Kemmerling, Ulrike, Gambino, Dinorah, Otero, Lucía, Olea Azar, Claudio, Rodríguez-Arce, Esteban
Format: Article
Language:English
Subjects:
Adducts
Antiparasitic agents
Biological activity
Cancer therapies
Chemotherapy
Clinical trials
Cytology
Disease
Drugs
Electron paramagnetic resonance
Electron spin
Electron spin resonance
Energy
Free radicals
Gold
Gold compounds
Ligands
Metal ions
Nitrogen dioxide
Oxidative stress
Parasites
Pharmaceutical industry
Protozoa
Redox properties
Spin resonance
thiosemicarbazones
Trypanosoma cruzi
Voltammetry
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Summary:In the search for a more effective chemotherapy for the treatment of Chagas’ disease, caused by Trypanosoma cruzi parasite, the use of gold compounds may be a promising approach. In this work, four gold(I) compounds [AuCl(HL)], (HL = bioactive 5-nitrofuryl containing thiosemicarbazones) were studied. The compounds were theoretically characterized, showing identical chemical structures with the metal ion located in a linear coordination environment and the thiosemicarbazones acting as monodentate ligands. Cyclic voltammetry and Electron Spin Resonance (ESR) studies demonstrated that the complexes could generate the nitro anion radical (NO2−) by reduction of the nitro moiety. The compounds were evaluated in vitro on the trypomastigote form of T. cruzi and human cells of endothelial morphology. The gold compounds studied showed activity in the micromolar range against T. cruzi. The most active compounds (IC50 of around 10 μM) showed an enhancement of the antiparasitic activity compared with their respective bioactive ligands and moderate selectivity. To get insight into the anti-chagasic mechanism of action, the intracellular free radical production capacity of the gold compounds was assessed by ESR and fluorescence measurements. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and redox cycling processes were characterized. The potential oxidative stress mechanism against T. cruzi was confirmed.
ISSN:2304-6740
2304-6740
DOI:10.3390/inorganics12050133