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A non-radiolabeled heme–GSH interaction test for the screening of antimalarial compounds

Garavito, Giovanny and Monje, Marie-Carmen and Maurel, Séverine and Valentin, Alexis and Nepveu, Françoise and Deharo, Eric A non-radiolabeled heme–GSH interaction test for the screening of antimalarial compounds. (2007) Experimental Parasitology, 116 (3). 311-313. ISSN 0014-4894

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Official URL: https://doi.org/10.1016/j.exppara.2007.01.005

Abstract

Intraerythrocytic Plasmodium produces large amounts of toxic heme during the digestion of hemoglobin, a parasite specific pathway. Heme is then partially biocristallized into hemozoin and mostly detoxified by reduced glutathione. We proposed an in vitro micro assay to test the ability of drugs to inhibit heme-glutathione dependent degradation. As glutathione and o-phthalaldehyde form a fluorescent adduct, we followed the extinction of the fluorescent signal when heme was added with or without antimalarial compounds. In this assay, 50 microM of amodiaquine, arthemether, chloroquine, methylene blue, mefloquine and quinine inhibited the interaction between glutathione (50 microM) and heme (50 microM), while atovaquone did not. Consequently, this test could detect drugs that can inhibit heme-GSH degradation in a fast, simple and specific way, making it suitable for high throughput screening of potential antimalarials.

Item Type:Article
HAL Id:hal-02143188
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Institut de Recherche pour le Développement - IRD (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UPS (FRANCE)
Other partners > Universidad Nacional de Colombia (COLOMBIA)
Laboratory name:
Funders:
European Union
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Deposited By: Loetitia MOYA
Deposited On:06 Mar 2019 11:58

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