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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/102463
Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death
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Abstract
Malaria is a life-threatening disease caused by different
species of the protozoan parasite Plasmodium, with P. falciparum
being the deadliest. Increasing parasitic resistance to existing
antimalarials makes the necessity of novel avenues to treat this
disease an urgent priority. The enzymes responsible for the
synthesis of phosphatidylcholine and phosphatidylethanolamine
are attractive drug targets to treat malaria as their selective
inhibition leads to an arrest of the parasite's growth and cures
malaria in a mouse model. We present here a detailed study that
reveals a mode of action for two P. falciparum choline kinase
inhibitors both in vitro and in vivo. The compounds present
distinct binding modes to the choline/ethanolamine-binding site
of P. falciparum choline kinase, reflecting different types of
inhibition. Strikingly, these compounds primarily inhibit the
ethanolamine kinase activity of the P. falciparum choline
kinase, leading to a severe decrease in the
phosphatidylethanolamine levels within P. falciparum, which
explains the resulting growth phenotype and the parasites death.
These studies provide an understanding of the mode of action,
and act as a springboard for continued antimalarial development
efforts selectively targeting P. falciparum choline kinase.
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SERRAN AGUILERA, Lucía, et al. Plasmodium falciparum Choline Kinase Inhibition Leads to a Major
Decrease in Phosphatidylethanolamine Causing Parasite Death. Scientific Reports. 2016. Vol. 6, num. 33189. ISSN 2045-2322. [consulted: 18 of June of 2026]. Available at: https://hdl.handle.net/2445/102463