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    Azole-based compounds as potential anti-Acanthamoeba agents
    (Royal Society of Chemistry, 2024) Qubais, Saeed, B.; Hamdy, R.; Akbar, N.; Sajeevan, S.E.; Khan, N.A.; Soliman, S.S.M.
    Acanthamoeba castellanii 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-Acanthamoeba activity with MIC50 values of 125.37 and 143.92 ?g 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 ?g 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-Acanthamoeba agents by both eliminating amoeba viability and preventing excystation, via 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 Acanthamoeba CYP51. They also display superior binding interactions. Further research is needed to understand their mechanisms and optimize their efficacy against Acanthamoeba infections. © 2024 RSC.
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    Nanomedicine: Patuletin-conjugated with zinc oxide exhibit potent effects against Gram-negative and Gram-positive bacterial pathogens
    (Springer Science and Business Media B.V., 2024) Khan, N.A.; Alvi, A.; Alqassim, S.; Akbar, N.; Khatoon, B.; Kawish, M.; Faizi S.
    With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO’ nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin’s effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work. © The Author(s), under exclusive licence to Springer Nature B.V. 2024.