Identification of Megazol metabolites from 2 models

Abstract : African Trypanosomiasis is endemic in nearly 30 countries in sub-Saharan Africa. The parasite responsible for this infection is Trypanosoma brucei, transmitted by the bite of glossina or tsetse fly. This parasitosis affects both animals (AAT - Animal African Trypanosomosis) and humans (HAT - Human African Trypanosomosis) and is fatal in absence of treatment. Its therapeutic care is complex and depends on trypanosome species, host and stage of the disease. Therefore, it is essential to find new treatments. Megazol, a molecule previously descripted with a trypanocid effect, has interesting derivates that are investigated in our work. The aim of our work is to highlight trypanocidal metabolites derived from megazol by two approaches: 1) an in vivo study on murine model then, 2) an approach of bioconversion by microorganisms. 1) Lots of mice received a dose of megazol at given times and a urine collection was carried out for analysis by high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) using GUS (General Unknown Screening) and MRM (Multiple Reaction Monitoring) methods. The results revealed 16 different ions. 2) The bioconversion approach by selecting microorganisms capable of transforming megazol by a combinatorial approach, after LC/MS-MS analysis, made it possible to show the formation of metabolites identical to those in the in vivo study. This detection confirms the fact that some fungal species are capable of mimicking mammalian metabolism. The production and purification of metabolites are underway to identify and study their activity and toxicity.
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Poster
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https://hal-unilim.archives-ouvertes.fr/hal-01936855
Contributeur : Elisabeth Grelier <>
Soumis le : mardi 27 novembre 2018 - 16:36:32
Dernière modification le : lundi 21 janvier 2019 - 15:05:24

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  • HAL Id : hal-01936855, version 1

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Clotilde Boudot, Emilie Pinault, Julien Bonnet, Didier Buisson, Bertrand Courtioux. Identification of Megazol metabolites from 2 models. Congrés Trypanosomatid Parasites from the field to the Lab, Dec 2017, Paris, France. ⟨hal-01936855⟩

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