Azole-based compounds as potential anti- Acanthamoeba agents

• Published in: MedChemComm 2024-05, Vol.15 (5), p.1578-1588
• Main Authors: Qubais Saeed, Balsam, Hamdy, Rania, Akbar, Noor, Sajeevan, Sreedevi Edathadan, Khan, Naveed Ahmed, Soliman, Sameh S M
• Format: Article
• Language: English
• Subjects: Acanthamoeba; Amoeba; Bioavailability; Complex formation; Cytotoxicity; Immune system; Molecular properties; Opportunist infection; Optimization; Public health
• ISSN: 2632-8682; 2040-2503; 2632-8682; 2040-2511
• DOI: 10.1039/d4md00029c

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- activity with MIC values of 125.37 and 143.92 μg mL , respectively. Interestingly, compounds T1, T4, T5 and T8 revealed profound anti-excystation activity with MIC at 32.01, 85.53, 19.54 and 80.57 μg mL , respectively, alongside limited cytotoxicity to human cells. The study underscores the potential of T1, T4, T5, and T8, thiazole-based compounds, as anti- agents by both eliminating amoeba viability and preventing excystation, 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 CYP51. They also display superior binding interactions. Further research is needed to understand their mechanisms and optimize their efficacy against infections.