ArticleBioorganic & medicinal chemistry letters2015
Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies.
Article in Bioorganic & medicinal chemistry letters, 2015. 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, 33 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
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.ACS infectious diseases · 2025Article
- Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights.Journal of medicinal chemistry · 2025Review
- β-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling.ACS infectious diseases · 2024Article
- Rational-Based Discovery of Novel β-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria.Pathogens (Basel, Switzerland) · 2022Article
- Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent AntimalarialsACS medicinal chemistry letters · 2022Article
- Malaria Box-Inspired Discovery ofACS medicinal chemistry letters · 2022Article
- Probing the B- & C-rings of the antimalarial tetrahydro-β-carboline MMV008138 for steric and conformational constraints.Bioorganic & medicinal chemistry letters · 2020Article
- Questioning the γ-gauche effect: stereoassignment of 1,3-disubstituted-tetrahydro-β-carbolines usingOrganic & biomolecular chemistry · 2019Article
- Synthesis and Evaluation of Antiplasmodial Efficacy of β-Carboline Derivatives against Murine Malaria.ACS omega · 2018Article
- 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.ACS infectious diseases · 2018Article
- Validation of Putative Apicoplast-Targeting Drugs Using a Chemical Supplementation Assay in Cultured Human Malaria Parasites.Antimicrobial agents and chemotherapy · 2018Article
- Molecular Mechanism of Action of Antimalarial Benzoisothiazolones: Species-Selective Inhibitors of the Plasmodium spp. MEP Pathway enzyme, IspD.Scientific reports · 2016Article
- Metabolomic Profiling of the Malaria Box Reveals Antimalarial Target Pathways.Antimicrobial agents and chemotherapy · 2016Article
- Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.PLoS pathogens · 2016Article
- New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium.Frontiers in microbiology · 2016Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Compounds that target isoprenoid biosynthesis in Plasmodium falciparum could be a welcome addition to malaria chemotherapy, since the methylerythritol phosphate (MEP) pathway used by the parasite is not present in humans. We previously reported that MMV008138 targets the apicoplast of P. falciparum and that its target in the MEP pathway differs from that of Fosmidomycin. In this Letter, we determine that the active stereoisomer of MMV008138 is 4a, which is (1R,3S)-configured. 2',4'-Disubstitution of the D ring was also found to be crucial for inhibition of the parasite growth. Limited variation of the C3-carboxylic acid substituent was carried out, and methylamide derivative 8a was found to be more potent than 4a; other amides, acylhydrazines, and esters were less potent. Finally, lead compounds 4a, 4e, 4f, 4h, 8a, and 8e did not inhibit growth of Escherichia coli, suggesting that protozoan-selective inhibition of the MEP pathway of P. falciparum can be achieved.
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