ArticleJournal of medicinal chemistry2012
Discovery of a Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase inhibitor (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Revisiting theNPJ drug discovery · 2025Article
- Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target inMicroorganisms · 2024Review
- Identifying inhibitors of β-haematin formation with activity against chloroquine-resistant Plasmodium falciparum malaria parasites via virtual screening approaches.Scientific reports · 2023Article
- Identification ofSaudi journal of biological sciences · 2022Article
- An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.Antimicrobial agents and chemotherapy · 2022Article
- Boosting the Discovery of Small Molecule Inhibitors of Glucose-6-Phosphate Dehydrogenase for the Treatment of Cancer, Infectious Diseases, and Inflammation.Journal of medicinal chemistry · 2022Review
- Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: characterization of the Plasmodium vivax enzyme and inhibitor studies.Malaria journal · 2019Article
- Predicted Biological Activity of Purchasable Chemical Space.Journal of chemical information and modeling · 2018Article
- A high susceptibility to redox imbalance of the transmissible stages of Plasmodium falciparum revealed with a luciferase-based mature gametocyte assay.Molecular microbiology · 2017Article
- The influence of host genetics on erythrocytes and malaria infection: is there therapeutic potential?Malaria journal · 2015Review
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Antimalarial NADPH-Consuming Redox-Cyclers As Superior Glucose-6-Phosphate Dehydrogenase Deficiency Copycats.Antioxidants & redox signaling · 2015Article
- Suitable in vitro Eimeria arloingi macromeront formation in host endothelial cells and modulation of adhesion molecule, cytokine and chemokine gene transcription.Parasitology research · 2015Article
- Small molecule screen for candidate antimalarials targeting Plasmodium Kinesin-5.The Journal of biological chemistry · 2014Article
- Classification of Plasmodium falciparum glucose-6-phosphate dehydrogenase inhibitors by support vector machine.Molecular diversity · 2013Article
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26 authors.
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Abstract
A high-throughput screen of the NIH's MLSMR collection of ∼340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (PfG6PD). PfG6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum , the bifunctional enzyme glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (PfGluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of PfGluPho. The lead compound identified from this effort, (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide, 11 (ML276), is a submicromolar inhibitor of PfG6PD (IC(50) = 889 nM). It is completely selective for the enzyme's human isoform, displays micromolar potency (IC(50) = 2.6 μM) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting PfG6PD in vivo are in progress.
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