# Amebicidal Effect of Adamantane–Azole Gold(I) Complexes: Cell Death Mechanisms and Synergistic Action with Chlorhexidine against Acanthamoeba castellanii

## TL;DR

This study shows that new gold-based compounds can effectively kill Acanthamoeba, a protozoan causing serious infections, with minimal toxicity and potential synergy with chlorhexidine.

## Contribution

The study introduces novel adamantane–azole gold(I) complexes with potent amoebicidal activity and identifies their synergistic effect with chlorhexidine.

## Key findings

- Complexes C2, C3, and C4 showed potent amoebicidal activity with IC50 values of 0.12, 14, and 6.2 μM.
- C4 triggered mitochondrial depolarization and phosphatidylserine exposure in Acanthamoeba.
- Molecular docking confirmed thioredoxin reductase as a potential target of the gold complexes.

## Abstract

Acanthamoeba spp. are free-living protozoa associated
with severe infections such as amebic keratitis and granulomatous
amebic encephalitis. The absence of effective treatments highlights
the need for new bioactive molecules targeting both trophozoite and
cyst forms. This study evaluated the anti-Acanthamoeba activity of adamantane-azole gold­(I) complexes (C1 and C4) and their
interaction with thioredoxin reductase (TrxR). Complexes C2, C3, and
C4 exhibited potent amoebicidal activity with IC50 values
of 0.12, 14, and 6.2 μM, respectively. They disrupted the cell
cycle and induced phosphatidylserine exposure, while C4 also triggered
mitochondrial depolarization. Ultrastructural alterations, synergy
with chlorhexidine, and absence of toxicity in vitro and in vivo models
were observed. Molecular docking confirmed TrxR as a potential target.
These findings demonstrate the therapeutic promise of C2, C3, and
C4 gold­(I) complexes against Acanthamoeba spp. infections,
combining potent activity with minimal toxicity and supporting further
investigation of their mechanisms of action.