Azole-based compounds as potential anti-<i>Acanthamoeba</i> agents

Abstract

<i>Acanthamoeba castellanii</i> is an opportunistic pathogen with public health implications, largely due to its invasive nature and non-specific symptoms. Our study focuses on the potential of azole compounds, particularly those with triazole scaffolds, as anti-amoebic agents. Out of 10 compounds, compounds T1 and T8 exhibited effective anti-<i>Acanthamoeba</i> activity with MIC₅₀ values of 125.37 and 143.92 μg mL^-1, respectively. Interestingly, compounds T1, T4, T5 and T8 revealed profound anti-excystation activity with MIC₅₀ at 32.01, 85.53, 19.54 and 80.57 μg mL^-1, respectively, alongside limited cytotoxicity to human cells. The study underscores the potential of T1, T4, T5, and T8, thiazole-based compounds, as anti-<i>Acanthamoeba</i> agents by both eliminating amoeba viability and preventing excystation, <i>via</i> preserving the amoeba in its latent cyst form, exposing them to elimination by the immune system. Notably, compounds T1, T4, T5, and T8 showed optimal molecular properties, moderate oral bioavailability, and stable complex formation with <i>Acanthamoeba</i> CYP51. They also display superior binding interactions. Further research is needed to understand their mechanisms and optimize their efficacy against <i>Acanthamoeba</i> infections.