ArticleMalaria journal2004
Anti-Plasmodium activity of ceramide analogs.
Article in Malaria journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
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- Erythrocyte sphingosine kinase regulates intraerythrocytic development of Plasmodium falciparum.Scientific reports · 2021Article
- Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.Nature communications · 2020Article
- First genome-wide association study of non-severe malaria in two birth cohorts in Benin.Human genetics · 2019Article
- Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis.Parasitology · 2018Review
- New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps.Scientific reports · 2016Article
- An integrative analysis of small molecule transcriptional responses in the human malaria parasite Plasmodium falciparum.BMC genomics · 2015Article
- Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum.Cell host & microbe · 2015Article
- Targeting lipid biosynthesis and salvage in apicomplexan parasites for improved chemotherapies.Nature reviews. Microbiology · 2013Review
- Antimalarial activity of axidjiferosides, new β-galactosylceramides from the African sponge Axinyssa djiferi.Marine drugs · 2013Article
- Network-based assessment of the selectivity of metabolic drug targets in Plasmodium falciparum with respect to human liver metabolism.BMC systems biology · 2012Article
- Sphingolipid analogues inhibit development of malaria parasites.ACS medicinal chemistry letters · 2012Article
- Potent inhibition of Acid ceramidase by novel B-13 analogues.Journal of lipids · 2011Article
- Sphingolipids in parasitic protozoa.Advances in experimental medicine and biology · 2010Review
- A sphingolipid inhibitor induces a cytokinesis arrest and blocks stage differentiation in Giardia lamblia.Antimicrobial agents and chemotherapy · 2008Article
- Mass spectrometry-based systems approach for identification of inhibitors of Plasmodium falciparum fatty acid synthase.Antimicrobial agents and chemotherapy · 2007Article
- Role of sphingolipids in microbial pathogenesis.Infection and immunity · 2006Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs.
methodsThe anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages) between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite.
resultsAnalogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range) than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range). The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target.
conclusionsIt has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the sphingoid core considerably influences the antiplasmodial activity and the selectivity of analogs when compared to their cytotoxicity on mammalian cells. By comparison with their inhibitory effect on cancer cell growth, the ceramide analogs might inhibit P. falciparum growth through modulation of the endogenous ceramide level.
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