The Anti-Parasite Action of Imidazole Derivatives Likely Involves Oxidative Stress but not HIF-1α Signaling.
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Date
2021-11-01
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Publisher
Elsevier
Abstract
Background: Therapeutic options for toxoplasmosis are limited. This fact underscores ongoing research efforts to
identify and develop better therapy. Previously, we reported the anti-parasitic potential of a new series of derivatives
of imidazole.
Objective: In the current investigation, we attempted the investigation of the possible action mechanism of few
promising anti-parasite imidazole derivatives namely C1 (bis-imidazole), C2 (phenyl-substituted 1H-imidazole)
and C3 (thiophene-imidazole)
Methods: We evaluated if oxidative stress, hypoxia as well as metabolic reprogramming of host L-tryptophan
pathway form part of the parasite growth inhibition by imidazoles. Anti-parasite assay was performed for imidazoles
at concentrations ranging from 0 to 10 μM, while pyrimethamine was used as reference drug to validate
assay.
Results: Imidazole compounds restricted parasite growth dose-dependently. However, in the presence of an
antioxidant (Trolox), L-tryptophan and/or CoCl2 (chemical inducer of hypoxia), the growth inhibitory efficacy of
imidazoles was appreciably abolished. Further, imidazole treatment led to elevated level of reactive oxygen
species, while reducing parasite mitochondrial membrane potential compared with control. In contrast, imidazole
had no effect on host HIF-1α level suggesting its exclusion in the anti-parasite action.
Conclusion: Taken together, imidazole-based compounds might restrict parasite growth by causing oxidative
stress. The findings provide new insight on the likely biochemical mechanisms of imidazoles as prospective antiparasite
therapy. Data gives new perspective that not only underscores the anti-parasite prospects of imidazoles,
but implicates the host L-tryptophan pathway as a feasible treatment option for T. gondii infections.
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Keywords
Anti-parasite, Imidazoles
Citation
Adeyemi OS, Eseola AO, Plass W, Kato K, Otuechere CA, Awakan OJ, Atolani O, Otohinoyi DA, Elebiyo TC, Evbuomwan IO (2021). The anti-parasite action of imidazole derivatives likely involves oxidative stress but not HIF-1α signaling. Chem Biol Interact. 349:109676. doi: 10.1016/j.cbi.2021.109676