ArticleACS infectious diseases2018
Biological Studies and Target Engagement of the 2- C-Methyl-d-Erythritol 4-Phosphate Cytidylyltransferase (IspD)-Targeting Antimalarial Agent (1 R,3 S)-MMV008138 and Analogs.
Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Effect of Stereochemistry on the Antiplasmodial Activity and Metabolomic Profile of Novel Tadalafil Analogues.ACS medicinal chemistry letters · 2026Article
- β-Carboline: a privileged scaffold from nature for potential antimalarial activity.RSC medicinal chemistry · 2025Review
- Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.ACS infectious diseases · 2025Article
- Synthetic account on indoles and their analogues as potential anti-plasmodial agents.Molecular diversity · 2025Review
- Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights.Journal of medicinal chemistry · 2025Review
- Innovations in Antimalarial Drug Discovery: New Targets and Leads.Current drug targets · 2025Review
- TargetingJournal of medicinal chemistry · 2024Article
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Cloning and Functional Characterization of 2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase (LiMCT) Gene in Oriental Lily (Lilium 'Sorbonne').Molecular biotechnology · 2024Article
- Bibliometric analysis of antimalarial drug resistance.Frontiers in cellular and infection microbiology · 2024Review
- Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite.Molecules (Basel, Switzerland) · 2023Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway.Pharmaceutics · 2022Article
- Malaria Box-Inspired Discovery ofACS medicinal chemistry letters · 2022Article
- Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent AntimalarialsACS medicinal chemistry letters · 2022Article
- Synthesis, Molecular Docking and Antiplasmodial Activities of New Tetrahydro-β-Carbolines.International journal of molecular sciences · 2021Article
- Immuno-antibiotics: targeting microbial metabolic pathways sensed by unconventional T cells.Immunotherapy advances · 2021Review
- Probing the B- & C-rings of the antimalarial tetrahydro-β-carboline MMV008138 for steric and conformational constraints.Bioorganic & medicinal chemistry letters · 2020Article
- Resistance to Some But Not Other Dimeric Lindenane Sesquiterpenoid Esters Is Mediated by Mutations in aACS infectious diseases · 2020Article
- Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Malaria continues to be one of the deadliest diseases worldwide, and the emergence of drug resistance parasites is a constant threat. Plasmodium parasites utilize the methylerythritol phosphate (MEP) pathway to synthesize isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are essential for parasite growth. Previously, we and others identified that the Malaria Box compound MMV008138 targets the apicoplast and that parasite growth inhibition by this compound can be reversed by supplementation of IPP. Further work has revealed that MMV008138 targets the enzyme 2- C-methyl-d-erythritol 4-phosphate cytidylyltransferase (IspD) in the MEP pathway, which converts MEP and cytidine triphosphate (CTP) to cytidinediphosphate methylerythritol (CDP-ME) and pyrophosphate. In this work, we sought to gain insight into the structure-activity relationships by probing the ability of MMV008138 analogs to inhibit PfIspD recombinant enzyme. Here, we report PfIspD inhibition data for fosmidomycin (FOS) and 19 previously disclosed analogs and report parasite growth and PfIspD inhibition data for 27 new analogs of MMV008138. In addition, we show that MMV008138 does not target the recently characterized human IspD, reinforcing MMV008138 as a prototype of a new class of species-selective IspD-targeting antimalarial agents.
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