ArticleEuropean journal of medicinal chemistry2014
Development of potent and selective Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) inhibitors that block the transmission of malaria to mosquitoes.
Article in European journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
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- De Novo Molecular Design and Bioactivity Prediction of Novel Hexahydroquinolines asBioinformatics and biology insights · 2026Article
- Anti-Cryptosporidium efficacy of BKI-1708, an inhibitor of Cryptosporidium calcium-dependent protein kinase 1.PLoS neglected tropical diseases · 2025Article
- Proteome selectivity profiling of photoaffinity probes derived from imidazopyrazine-kinase inhibitors.Communications chemistry · 2025Article
- Employing Hexahydroquinolines asAdvances and applications in bioinformatics and chemistry : AABC · 2024Article
- Identification of Fungus-Derived Natural Products as New Antigiardial Scaffolds.Microbiology spectrum · 2023Article
- 7H-Pyrrolo[2,3-d]pyrimidine-4-amines as Potential Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinases.ChemMedChem · 2022Article
- Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy.Antimicrobial agents and chemotherapy · 2022Article
- 1,2,3-Triazolyl-tetrahydropyrimidine Conjugates as Potential Sterol Carrier Protein-2 Inhibitors: Larvicidal Activity against the Malaria VectorMolecules (Basel, Switzerland) · 2022Article
- Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.Frontiers in cellular and infection microbiology · 2022Review
- Drug Target Validation of the Protein KinaseMicrobiology spectrum · 2021Article
- Calcium in the Backstage of Malaria Parasite Biology.Frontiers in cellular and infection microbiology · 2021Review
- CDPKs: The critical decoders of calcium signal at various stages of malaria parasite development.Computational and structural biotechnology journal · 2021Review
- One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases.Veterinary parasitology · 2021Review
- An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice.International journal of antimicrobial agents · 2020Article
- Overlapping and distinct roles of CDPK family members in the pre-erythrocytic stages of the rodent malaria parasite, Plasmodium berghei.PLoS pathogens · 2020Article
- Taming the Boys for Global Good: Contraceptive Strategy to Stop Malaria Transmission.Molecules (Basel, Switzerland) · 2020Review
- Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria VectorMolecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Malaria remains a major health concern for a large percentage of the world's population. While great strides have been made in reducing mortality due to malaria, new strategies and therapies are still needed. Therapies that are capable of blocking the transmission of Plasmodium parasites are particularly attractive, but only primaquine accomplishes this, and toxicity issues hamper its widespread use. In this study, we describe a series of pyrazolopyrimidine- and imidazopyrazine-based compounds that are potent inhibitors of PfCDPK4, which is a calcium-activated Plasmodium protein kinase that is essential for exflagellation of male gametocytes. Thus, PfCDPK4 is essential for the sexual development of Plasmodium parasites and their ability to infect mosquitoes. We demonstrate that two structural features in the ATP-binding site of PfCDPK4 can be exploited in order to obtain potent and selective inhibitors of this enzyme. Furthermore, we demonstrate that pyrazolopyrimidine-based inhibitors that are potent inhibitors of the in vitro activity of PfCDPK4 are also able to block Plasmodium falciparum exflagellation with no observable toxicity to human cells. This medicinal chemistry effort serves as a valuable starting point in the development of safe, transmission-blocking agents for the control of malaria.
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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.