ArticleScientific reports2016
Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Novel sugar-conjugated Knoevenagel condensate curcumin derivatives as promising bioactive hybrids with antimalarial potential.RSC advances · 2026Article
- Shared host, distinct invaders: metabolomic footprints of plasmodium and babesia in host red cells.Current opinion in hematology · 2025Review
- Inner-mitochondrial membrane protein PfMPV17 is linked to P. falciparum in vitro resistance to the indoloquinolizidine alkaloid alstonine.The Journal of antimicrobial chemotherapy · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Dobinin K Displays Antiplasmodial Activity through Disruption ofMolecules (Basel, Switzerland) · 2024Article
- A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays.Communications biology · 2023Article
- A screen of drug-like molecules identifies chemically diverse electron transport chain inhibitors in apicomplexan parasites.PLoS pathogens · 2023Article
- Novel Therapeutics for Malaria.Pharmaceutics · 2023Review
- The delayed bloodstream clearance ofFrontiers in cellular and infection microbiology · 2023Article
- Current and emerging target identification methods for novel antimalarials.International journal for parasitology. Drugs and drug resistance · 2022Review
- Design of Anti-infectious Agents from Lawsone in a Three-Component Reaction with Aldehydes and Isocyanides.ACS omega · 2022Article
- The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.Traffic (Copenhagen, Denmark) · 2022Article
- Optimized Pyridazinone Nutrient Channel Inhibitors Are Potent and Specific Antimalarial Leads.Molecular pharmacology · 2022Article
- In-depth biological analysis of alteration in Plasmodium knowlesi-infected red blood cells using a noninvasive optical imaging technique.Parasites & vectors · 2022Article
- Plasmodium vivax infection compromises reticulocyte stability.Nature communications · 2021Article
- Duration of Storage Reduced Erythrocytes Profiles andJournal of blood medicine · 2021Article
- The relative rate of kill of the MMV Malaria Box compounds provides links to the mode of antimalarial action and highlights scaffolds of medicinal chemistry interest.The Journal of antimicrobial chemotherapy · 2020Article
- Antimalarial Drug Resistance and Novel Targets for Antimalarial Drug Discovery.Infection and drug resistance · 2020Review
- Recent Progress in the Development of New Antimalarial Drugs with Novel Targets.Drug design, development and therapy · 2020Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium parasites are responsible for the devastating disease malaria that affects hundreds of millions of people each year. Blood stage parasites establish new permeability pathways (NPPs) in infected red blood cell membranes to facilitate the uptake of nutrients and removal of parasite waste products. Pharmacological inhibition of the NPPs is expected to lead to nutrient starvation and accumulation of toxic metabolites resulting in parasite death. Here, we have screened a curated library of antimalarial compounds, the MMV Malaria Box, identifying two compounds that inhibit NPP function. Unexpectedly, metabolic profiling suggested that both compounds also inhibit dihydroorotate dehydrogense (DHODH), which is required for pyrimidine synthesis and is a validated drug target in its own right. Expression of yeast DHODH, which bypasses the need for the parasite DHODH, increased parasite resistance to these compounds. These studies identify two potential candidates for therapeutic development that simultaneously target two essential pathways in Plasmodium, NPP and DHODH.
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