Experimental pharmacological study of the antimalarial activity of a compound of synthesis: the methylthioninium chloride
Identifieur interne : 000093 ( Hal/Curation ); précédent : 000092; suivant : 000094Experimental pharmacological study of the antimalarial activity of a compound of synthesis: the methylthioninium chloride
Auteurs : Giovanny Garavito [France]Source :
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- topic : Pharmacologie.
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Abstract
We studied the antimalarial activity of methylene blue (BM), which was the first synthetic molecule used in the treatment of malaria. We showed that BM is active on Plasmodium falciparum strains from different geographical origins and chloroquino-sensitivities (IC50<10nM). It is also active on the blood cycle of rodent malaria (ED50<15mg/Kg), but not on the hepatic phase. The most sensitive erythrocytic stages are young stages. Associations with traditional treatments are: antagonist with amodiaquine; antagonism-additive with atovaquone, doxycycline, pyrimethamine; additive-pas d'interaction with artemether, chloroquine, mefloquine, primaquine and synergistic with quinine. We showed by spectrometry UV, TLC and mass spectrometry, that there is no association between BM and hem. We also developed a new technique to measure the transformation of hem by the glutathione and to measure the activity of drugs on this transformation.
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<front><div type="abstract" xml:lang="en"> <p>We studied the antimalarial activity of methylene blue (BM), which was the first synthetic molecule used in the treatment of malaria. We showed that BM is active on Plasmodium falciparum strains from different geographical origins and chloroquino-sensitivities (IC50<10nM). It is also active on the blood cycle of rodent malaria (ED50<15mg/Kg), but not on the hepatic phase. The most sensitive erythrocytic stages are young stages. Associations with traditional treatments are: antagonist with amodiaquine; antagonism-additive with atovaquone, doxycycline, pyrimethamine; additive-pas d'interaction with artemether, chloroquine, mefloquine, primaquine and synergistic with quinine. We showed by spectrometry UV, TLC and mass spectrometry, that there is no association between BM and hem. We also developed a new technique to measure the transformation of hem by the glutathione and to measure the activity of drugs on this transformation.</p>
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<abstract xml:lang="en"> <p>We studied the antimalarial activity of methylene blue (BM), which was the first synthetic molecule used in the treatment of malaria. We showed that BM is active on Plasmodium falciparum strains from different geographical origins and chloroquino-sensitivities (IC50<10nM). It is also active on the blood cycle of rodent malaria (ED50<15mg/Kg), but not on the hepatic phase. The most sensitive erythrocytic stages are young stages. Associations with traditional treatments are: antagonist with amodiaquine; antagonism-additive with atovaquone, doxycycline, pyrimethamine; additive-pas d'interaction with artemether, chloroquine, mefloquine, primaquine and synergistic with quinine. We showed by spectrometry UV, TLC and mass spectrometry, that there is no association between BM and hem. We also developed a new technique to measure the transformation of hem by the glutathione and to measure the activity of drugs on this transformation.</p>
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<abstract xml:lang="fr"> <p>Nous nous sommes intéressés à l'activité antipaludique du bleu de méthylène (BM), qui fut la première molécule de synthèse utilisée dans le traitement des accès palustres. Nous avons montré que le BM est actif sur des souches cultivées de Plasmodium falciparum d'origines géographiques et de chloroquino-sensibilités différentes (CI50<10nM). Il est aussi actif sur le cycle sanguin de Plasmodium murin (DE50<15mg/Kg), mais pas sur la phase hépatique. Les stades érythrocytaires les plus sensibles sont les stades jeunes. Les associations avec les traitements classiques sont de type : antagoniste avec amodiaquine ; antagonisme-additif avec atovaquone, doxycycline, pyrimethamine ; additive-pas d'interaction avec artemether, chloroquine, mefloquine, primaquine et synergique avec la quinine. Nous avons montré par spectrométrie UV, CCM et spectrométrie de masse, qu'il n'y a pas de liaison entre le BM et l'hème. Nous avons également mis au point une nouvelle technique pour mesurer la transformation de l'hème par le glutathion et mesurer ainsi l'activité des drogues sur cette transformation.</p>
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