Please use this identifier to cite or link to this item: http://hdl.handle.net/10637/5541

Plasmodium falciparum: Stage speciWc eVects of a selective inhibitor of lactate dehydrogenase

Title: Plasmodium falciparum: Stage speciWc eVects of a selective inhibitor of lactate dehydrogenase
Authors : Vivas, Livia
Easton, Anna
Kendrick, Howard
Cameron, Angus
Lavandera Díaz, José Luis
Barros, David
Gómez de las Heras, Federico
Brady, R. Leo
Croft, Simon L.
Keywords: Compuestos heterocíclicos.Lactate dehydrogenaseIntraerythrocytic cycle
Abstract: Plasmodium falciparum lactate dehydrogenase (PfLDH) is essential for ATP generation. Based on structural diVerences within the active site between P. falciparum and human LDH, we have identiWed a series of heterocyclic azole-based inhibitors that selectively bind within the PfLDH but not the human LDH (hLDH) active site and showed anti-malarial activity in vitro and in vivo. Here we expand on an azole, OXD1, from this series and found that the anti-P. falciparum activity was retained against a panel of strains independently of their anti-malarial drug sensitivity proWle. Trophozoites had relatively higher PfLDH enzyme activity and PfLDH-RNA expression levels than rings and were the most susceptible stages to OXD1 exposure. This is probably linked to their increased energy requirements and consistent with glycolysis being an essential metabolic pathway for parasite survival within the erythrocyte. Further structural elaboration of these azoles could lead to the identiWcation of compounds that target P. falciparum through such a novel mechanism and with more potent anti-malarial activity.
Description: En: Experimental Parasitology. ISSN 0014-4894. v. 111, 2005, págs 105-114
URI: http://hdl.handle.net/10637/5541
Rights : http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
Issue Date: 1-Nov-2005
Center : Universidad San Pablo-CEU
Appears in Collections:Medicina





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