Garavito G., Monje M. C., Maurel S., Valentin A., Nepveu Françoise, Deharo Eric. (2007). A non-radiolabeled heme-GSH interaction test for the screening of antimalarial compounds. Experimental Parasitology, 116 (3), p. 311-313. ISSN 0014-4894.
Titre du document
A non-radiolabeled heme-GSH interaction test for the screening of antimalarial compounds
Garavito G., Monje M. C., Maurel S., Valentin A., Nepveu Françoise, Deharo Eric
Source
Experimental Parasitology, 2007,
116 (3), p. 311-313 ISSN 0014-4894
Intraerythrocytic Plasmodium produces large amounts of toxic heme during the digestion of hemoglobin, a parasite specific pathway. Heme is then partially biocristallized into hemozin 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 mu M of amodiaquine, arthemether, chloroquine, methylene blue, mefloquine and quinine inhibited the interaction between glutathione (50 mu M) and heme (50 mu M), 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.
