ArticleACS infectious diseases2020
Probing the Open Global Health Chemical Diversity Library for Multistage-Active Starting Points for Next-Generation Antimalarials.
Article in ACS infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Vicinal disubstitution of alkyl C-X synthons via alkene radical cation generation.Science (New York, N.Y.) · 2026Article
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- A Machine Learning Platform for Isoform-Specific Identification and Profiling of Human Carbonic Anhydrase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Development and experimental validation of a machine learning model for the prediction of new antimalarials.BMC chemistry · 2025Article
- Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.Journal of medicinal chemistry · 2025Article
- The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods.Nucleic acids research · 2024Article
- Repurposing the Open Global Health Library for the discovery of novel Mpro destabilizers with scope as broad-spectrum antivirals.Frontiers in pharmacology · 2024Article
- Design of the Global Health chemical diversity library v2 for screening against infectious diseases.PLoS neglected tropical diseases · 2023Article
- Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity.Journal of medicinal chemistry · 2023Article
- Machine Learning Approaches Identify Chemical Features for Stage-Specific Antimalarial Compounds.ACS omega · 2023Article
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- 7-ACS infectious diseases · 2023Article
- Promising antimalarial hits from phenotypic screens: a review of recently-described multi-stage actives and their modes of action.Frontiers in cellular and infection microbiology · 2023Review
- New Transmission-Selective Antimalarial Agents through Hit-to-Lead Optimization of 2-([1,1'-Biphenyl]-4-carboxamido)benzoic Acid Derivatives.Chembiochem : a European journal of chemical biology · 2022Article
- Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs.Nature communications · 2022Article
- Streamlined and Robust Stage-Specific Profiling of Gametocytocidal Compounds AgainstFrontiers in cellular and infection microbiology · 2022Article
- Phthalimide analogs for antimalarial drug discovery.RSC medicinal chemistry · 2021Review
- Prioritization of Molecular Targets for Antimalarial Drug Discovery.ACS infectious diseases · 2021Article
- High-content approaches to anthelmintic drug screening.Trends in parasitology · 2021Review
- MalDA, Accelerating Malaria Drug Discovery.Trends in parasitology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Most phenotypic screens aiming to discover new antimalarial chemotypes begin with low cost, high-throughput tests against the asexual blood stage (ABS) of the malaria parasite life cycle. Compounds active against the ABS are then sequentially tested in more difficult assays that predict whether a compound has other beneficial attributes. Although applying this strategy to new chemical libraries may yield new leads, repeated iterations may lead to diminishing returns and the rediscovery of chemotypes hitting well-known targets. Here, we adopted a different strategy to find starting points, testing ∼70,000 open source small molecules from the Global Health Chemical Diversity Library for activity against the liver stage, mature sexual stage, and asexual blood stage malaria parasites in parallel. In addition, instead of using an asexual assay that measures accumulated parasite DNA in the presence of compound (SYBR green), a real time luciferase-dependent parasite viability assay was used that distinguishes slow-acting (delayed death) from fast-acting compounds. Among 382 scaffolds with the activity confirmed by dose response (<10 μM), we discovered 68 novel delayed-death, 84 liver stage, and 68 stage V gametocyte inhibitors as well. Although 89% of the evaluated compounds had activity in only a single life cycle stage, we discovered six potent (half-maximal inhibitory concentration of <1 μM) multistage scaffolds, including a novel cytochrome bc1 chemotype. Our data further show the luciferase-based assays have higher sensitivity. Chemoinformatic analysis of positive and negative compounds identified scaffold families with a strong enrichment for activity against specific or multiple stages.
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