Understanding the biology of the Plasmodium falciparum apicoplast; an excellent target for antimalarial drug development

Life Sciences ◽  
2016 ◽  
Vol 158 ◽  
pp. 104-110 ◽  
Author(s):  
Arnish Chakraborty
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Antimalarial Drug

scholarly journals Plasmodium falciparum: new molecular targets with potential for antimalarial drug development

2009 ◽  
Vol 7 (9) ◽  
pp. 1087-1098 ◽  
Author(s):  
Donald L Gardiner ◽  
Tina S Skinner-Adams ◽  
Christopher L Brown ◽  
Katherine T Andrews ◽  
Colin M Stack ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Antimalarial Drug ◽  
Molecular Targets ◽  
New Molecular Targets

Antimalarial Drugs as Inspiration for Herbicides

2020 ◽  
Vol 31 (5) ◽  
pp. 216-220
Author(s):  
Joshua S. Mylne ◽  
Keith A. Stubbs
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Herbicide Resistance ◽  
Antimalarial Drug ◽  
Antimalarial Drugs ◽  
Malarial Parasite ◽  
Malaria Research ◽  
Close Relationship ◽  
Popular Subject ◽  
Drug Leads

In addition to good stewardship, the unabated rise in herbicide resistance and dearth of truly new herbicides demands that new molecules be found. Over 30 years ago, a chloroplast-like organelle was found in the malarial parasite Plasmodium falciparum and herbicides demonstrated a close relationship existed to plants. Recently this idea was turned on its head by exploiting the boom in malaria research to search for new herbicide chemistry and it provided interesting starting points for development. The merit of such an approach is underlined by tetflupyrolimet, the first truly novel herbicide in 30 years, and whose target has been a popular subject for antimalarial drug development for 15 years. Which other antimalarial targets, drugs and drug leads might reach across the parasite-plant divide to inspire new herbicides?

Novel inhibitors of the Plasmodium falciparum electron transport chain

Parasitology ◽  
2014 ◽  
Vol 141 (1) ◽  
pp. 50-65 ◽  
Author(s):  
P. A. STOCKS ◽  
V. BARTON ◽  
T. ANTOINE ◽  
G. A. BIAGINI ◽  
S. A. WARD ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Electron Transport ◽  
Drug Development ◽  
Antimalarial Drug ◽  
Electron Transport Chain ◽  
Type Ii ◽  
Dihydroorotate Dehydrogenase ◽  
Cytochrome Bc ◽  
Transport Chain ◽  
Promising Area

SUMMARYDue to an increased need for new antimalarial chemotherapies that show potency against Plasmodium falciparum, researchers are targeting new processes within the parasite in an effort to circumvent or delay the onset of drug resistance. One such promising area for antimalarial drug development has been the parasite mitochondrial electron transport chain (ETC). Efforts have been focused on targeting key processes along the parasite ETC specifically the dihydroorotate dehydrogenase (DHOD) enzyme, the cytochrome bc1 enzyme and the NADH type II oxidoreductase (PfNDH2) pathway. This review summarizes the most recent efforts in antimalarial drug development reported in the literature and describes the evolution of these compounds.

scholarly journals Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor

2014 ◽  
Vol 59 (1) ◽  
pp. 686-689 ◽  
Author(s):  
Jennifer L. Guler ◽  
John White ◽  
Margaret A. Phillips ◽  
Pradipsinh K. Rathod
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Cross Talk ◽  
Antimalarial Drug ◽  
Pyrimidine Biosynthesis ◽  
Dihydroorotate Dehydrogenase ◽  
Development Programs ◽  
Genetic Cross ◽  
High Level ◽  
Level Resistance

ABSTRACTAtovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such “genetic cross talk” between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.

Antimalarial Drug Targets and Drugs Targeting Dolichol Metabolic Pathway of Plasmodium falciparum

2014 ◽  
Vol 15 (4) ◽  
pp. 374-409 ◽  
Author(s):  
Tabish Qidwai ◽  
Avantika Priya ◽  
Nihal Khan ◽  
Himanshu Tripathi ◽  
Feroz Khan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Metabolic Pathway ◽  
Antimalarial Drug ◽  
Drug Targets

scholarly journals Identification of Heparin Modifications and Polysaccharide Inhibitors of Plasmodium falciparum Merozoite Invasion That Have Potential for Novel Drug Development

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Michelle J. Boyle ◽  
Mark Skidmore ◽  
Benjamin Dickerman ◽  
Lynsay Cooper ◽  
Anthony Devlin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Inhibitory Activity ◽  
Sulfated Polysaccharides ◽  
Merozoite Invasion ◽  
Content Type ◽  
Molecular Weights ◽  
Falciparum Merozoite ◽  
Successful Control ◽  
Novel Drug

ABSTRACT Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing and the development of new drug families is needed to maintain malaria control. Current antimalarials target the intraerythrocytic developmental stage of the Plasmodium falciparum life cycle. However, the invasive extracellular parasite form, the merozoite, is also an attractive target for drug development. We have previously demonstrated that heparin-like molecules, including those with low molecular weights and low anticoagulant activities, are potent and specific inhibitors of merozoite invasion and blood-stage replication. Here we tested a large panel of heparin-like molecules and sulfated polysaccharides together with various modified chemical forms for their inhibitory activity against P. falciparum merozoite invasion. We identified chemical modifications that improve inhibitory activity and identified several additional sulfated polysaccharides with strong inhibitory activity. These studies have important implications for the further development of heparin-like molecules as antimalarial drugs and for understanding merozoite invasion.

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