Volume 275, February 2026, 113131Author links open overlay panel, , , , , , , , Highlights•

First novel cationic gold(I)-thiosemicarbazone compounds.

•

Gold compounds exhibited activity and selectivity against Trypanosoma cruzi.

•

Aurophilic interactions play a key role in antiparasitic activity.

•

Mitochondria-mediated apoptotic cell death.

•

DNA interaction.

Abstract

Searching for more effective chemotherapeutic agents for the treatment of American Trypanosomiasis, a disease caused by the parasite Trypanosoma cruzi (T. cruzi), the development of gold(I) compounds represents a promising strategy. In this work, four new cationic gold(I) compounds, [Au(HL)₂]Cl, where HL = 5-nitrofuryl-containing thiosemicarbazones, were synthesized and characterized in the solid state and in DMSO solution. Their cationic and radical structures were experimentally and theoretically studied. The formation of intermolecular aurophilic interactions and the lipophilicity of the complexes were also analyzed. Three gold(I) compounds displayed micromolar IC₅₀ values (around 10 μM) against T. cruzi bloodstream trypomastigotes and showed moderate selectivity towards the parasites with respect to human cells of endothelial morphology. Two of these complexes were more active than their respective thiosemicarbazone ligands and exhibited antiparasitic activity comparable to that of Nifurtimox. Lipophilicity and the presence of aurophilic interactions appear to play a key role in their antitrypanosomal activity. The active gold(I) compounds induced cytosolic reactive oxygen species (ROS) generation, disrupted mitochondrial membrane potential, and promoted mitochondrial ROS production, suggesting they may act as crucial precursors to mitochondria-mediated apoptotic cell death. In addition, DNA competitive binding with ethidium bromide, evaluated by fluorescence measurements, demonstrated that the compounds interact with this biomolecule. Overall, these three active gold(I) complexes can be considered promising hits for the development of prospective agents against T. cruzi.

Graphical abstractCationic gold(I) compounds with 5-nitrofuryl containing thiosemicarbazone ligands as promising antitrypanosomal agents.Download: Download high-res image (94KB)Download: Download full-size imageKeywords

Gold

Thiosemicarbazones

Trypanosoma cruzi

Free radicals

Mitochondria

DNA

AbbreviationsNTD

Neglected tropical disease

T. cruzi

Trypanosoma cruzi

WHO

World Health Organization

HL

5-nitrofuryl containing thiosemicarbazone ligands

ROS

Reactive Oxygen Species

p-TsOH

p-toluenesulfonic acid

FTIR

Fourier transform infrared spectroscopy

ATR

Attenuated Total Reflection

NMR

nuclear magnetic resonance

1H NMR

proton nuclear magnetic resonance

13C NMR

carbon nuclear magnetic resonance

HMBC

heteronuclear multiple bond correlation

UV-Vis

ultraviolet-visible spectroscopy

ESR

electron spin resonance

TBAP

tetrabutyl ammonium perchlorate

TLC

thin layer chromatography

PBS

phosphate-buffered saline

MOI

multiplicity of infection

RPMI

Roswell Park Memorial Institute

FBSi

inactivated fetal bovine serum

MTT

3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide

DMEM

Dulbecco's Modified Eagle's Medium

DCFH2-DA

2′,7′-dihydrodichlorofluorescein diacetate

HBSS

Hanks' balanced salt solution

ΔΨm

mitochondrial membrane potential

TMRM

tetramethylrhodamine methyl ester

CCCP

carbonyl cyanide m-chlorophenylhydrazone

KSV

Stern–Volmer constant

Epc

cathodic peak potential

E2PERT

second-order perturbation analysis

Data availability

No data was used for the research described in the article.

View Abstract

© 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.