Identification of Metabolites Derived from the Anti-trypanosomal Drug Megazol

Clotilde Boudot, Emilie Pinault, Eden Lebrault, Julien Bonnet, Vincent Sol, Bertrand Courtioux


Background: African Trypanosomiasis is an endemic vector-borne parasitic disease in sub-Saharan Africa. It is caused by different parasites of the genus Trypanosoma and is transmitted through a tsetse fly (Glossina sp.) bite during a blood meal. This neglected tropical disease remains difficult to control due to the complexity of treatment protocols and use of toxic drugs. Over the decades, nitroimidazole compounds have been promising molecules for anti-parasite therapy. One of them, megazol, has proven to be an effective anti-trypanosomal drug, but interest dropped after reports were published concerning its mutagenic properties. Objectived: We therefore decided to characterize and identify megazol metabolites, with the hypothesis that they could be less toxic. Methods: We treated groups of mice with different derivatives and then detected metabolites by high performance liquid chromatography combined with mass spectrometry in urine, feces, and plasma samples from mice. Results: In vivo results showed that eleven metabolites were detected in urine (M1 to M11); six metabolites were detected in plasma (M1a/b, M2a/b, M5, M7a/b M9, andM10a/b) and in feces, only two (M1 a/b and M5) were found. Conclusions: The structures of metabolites were deduced using chromatograms and mass spectra data combined with usual metabolic patterns.



megazol, metabolites, HPLC-MS/MS, mice fluids


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