Azole-based compounds as potential anti-Acanthamoeba agents.

Area of Science:

• Infectious Diseases
• Medicinal Chemistry
• Parasitology

Background:

• Acanthamoeba castellanii is an opportunistic pathogen causing public health concerns due to its invasive nature and vague symptoms.
• Azole compounds, especially those with triazole scaffolds, are being investigated for their anti-parasitic properties.

Purpose of the Study:

• To evaluate the anti-amoebic potential of novel azole compounds against Acanthamoeba castellanii.
• To assess the compounds' efficacy in inhibiting both amoeba viability and excystation, while evaluating their cytotoxicity to human cells.

Main Methods:

• Screening of ten azole compounds for anti-amoebic activity.
• Determination of minimum inhibitory concentration 50 (MIC50) for amoeba viability and anti-excystation.
• Cytotoxicity assays on human cells.
• In silico analysis of molecular properties, oral bioavailability, and binding interactions with Acanthamoeba CYP51.

Main Results:

• Compounds T1 and T8 demonstrated significant anti-Acanthamoeba activity (MIC50 values of 125.37 and 143.92 μg mL−1).
• Compounds T1, T4, T5, and T8 exhibited potent anti-excystation activity (MIC50 values ranging from 19.54 to 85.53 μg mL−1) with limited cytotoxicity.
• These selected compounds possess favorable molecular properties, moderate oral bioavailability, and strong binding affinity to Acanthamoeba CYP51.

Conclusions:

• Thiazole-based compounds T1, T4, T5, and T8 are promising anti-Acanthamoeba agents.
• Their dual action of eliminating amoeba viability and preventing excystation offers a novel therapeutic strategy.
• Further investigation into their mechanisms and optimization is warranted for treating Acanthamoeba infections.