ArticleJournal of chemical information and modeling2016
Identification of New Human Malaria Parasite Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors by Pharmacophore and Structure-Based Virtual Screening.
Article in Journal of chemical information and modeling, 2016. 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, 67 citations in OpenAlex.
- New thinking for the next generation of antimalarials.EMBO molecular medicine · 2026Review
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Article
- Characterisation of plasmodial transketolases and identification of potential inhibitors: an in silico study.Malaria journal · 2020Article
- Driving antimalarial design through understanding of target mechanism.Biochemical Society transactions · 2020Review
- A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation.Molecules (Basel, Switzerland) · 2020Article
- Pharmacophore-Based Virtual Screening Toward the Discovery of Novel Anti-echinococcal Compounds.Frontiers in cellular and infection microbiology · 2020Article
- In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model.Science translational medicine · 2019Article
- The Development of Novel Compounds Against Malaria: Quinolines, Triazolpyridines, Pyrazolopyridines and Pyrazolopyrimidines.Molecules (Basel, Switzerland) · 2019Review
- Synthesis and Antiplasmodial Activity of 1,2,3-Triazole-Naphthoquinone Conjugates.Molecules (Basel, Switzerland) · 2019Article
- Enzymatic Transition States and Drug Design.Chemical reviews · 2018Review
- Selection ofProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Insights into Integrated Lead Generation and Target Identification in Malaria and Tuberculosis Drug Discovery.Accounts of chemical research · 2017Article
- Article
- Oral Multiple Sclerosis Drugs Inhibit theFrontiers in cellular and infection microbiology · 2017Article
- Drug target identification in protozoan parasites.Expert opinion on drug discovery · 2016Review
- Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway, which the Plasmodium falciparum relies on exclusively for survival, has emerged as a promising target for antimalarial drugs. In an effort to discover new and potent PfDHODH inhibitors, 3D-QSAR pharmacophore models were developed based on the structures of known PfDHODH inhibitors and the validated Hypo1 model was used as a 3D search query for virtual screening of the National Cancer Institute database. The virtual hit compounds were further filtered based on molecular docking and Molecular Mechanics/Generalized Born Surface Area binding energy calculations. The combination of the pharmacophore and structure-based virtual screening resulted in the identification of nine new compounds that showed >25% inhibition of PfDHODH at a concentration of 10 μM, three of which exhibited IC50 values in the range of 0.38-20 μM. The most active compound, NSC336047, displayed species-selectivity for PfDHODH over human DHODH and inhibited parasite growth with an IC50 of 26 μM. In addition to this, 13 compounds inhibited parasite growth with IC50 values of ≤ 50 μM, 4 of which showed IC50 values in the range of 5-12 μM. These compounds could be further explored in the identification and development of more potent PfDHODH and parasite growth inhibitors.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.