ArticleChemMedChem2022
Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2.
Article in ChemMedChem, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Site-Selective C6-β-Aminoalkylation of Tetrahydroquinolines withThe Journal of organic chemistry · 2026Article
- Hepatoprotective Effects of Fused Pyridine Derivatives: Regulation of the TGF-β/Smad, miR-21/Smad7, and PPARγ Pathways in Carbon Tetrachloride-Induced Liver Fibrosis.Drug design, development and therapy · 2026Article
- Antimalarial Drug Discovery from Natural and Synthetic Sources.Current medicinal chemistry · 2025Review
- The hepatoprotective effect of 4-phenyltetrahydroquinolines on carbon tetrachloride induced hepatotoxicity in rats through autophagy inhibition.Biological research · 2024Article
- Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2.ChemMedChem · 2022Article
- The malaria parasite chaperonin containing TCP-1 (CCT) complex: Data integration with other CCT proteomes.Frontiers in molecular biosciences · 2022Article
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 (2) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 (PfeEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline (2) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency.
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