ArticleThe Journal of infectious diseases2012
Pharmacological validation of Trypanosoma brucei phosphodiesterases as novel drug targets.
Article in The Journal of infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 93 citations in OpenAlex.
- Adhesion ofmSphere · 2024Article
- A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in Trypanosoma congolense.PLoS pathogens · 2024Article
- Discovery of 5-Phenylpyrazolopyrimidinone Analogs as Potent Antitrypanosomal Agents with In Vivo Efficacy.Journal of medicinal chemistry · 2023Article
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- To Target or Not to TargetInternational journal of molecular sciences · 2023Article
- Cloning and Characterization ofInternational journal of molecular sciences · 2023Article
- Novel kinetoplastid-specific cAMP binding proteins identified by RNAi screening for cAMP resistance inFrontiers in cellular and infection microbiology · 2023Article
- A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission.Nature communications · 2022Article
- Perspectives for a new drug candidate for Chagas disease therapy.Memorias do Instituto Oswaldo Cruz · 2022Article
- Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei.Molecular microbiology · 2021Review
- Tetrahydrophthalazinone Inhibitor of Phosphodiesterase withAntimicrobial agents and chemotherapy · 2021Article
- Discovery of Amoebicidal Compounds by Combining Computational and Experimental Approaches.Antimicrobial agents and chemotherapy · 2021Article
- Large-Scale Phylogenetic Analysis of Trypanosomatid Adenylate Cyclases Reveals Associations with Extracellular Lifestyle and Host-Pathogen Interplay.Genome biology and evolution · 2020Article
- Efficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2020Article
- Cloning and functional complementation of ten Schistosoma mansoni phosphodiesterases expressed in the mammalian host stages.PLoS neglected tropical diseases · 2020Article
- Discovery of Diaryl Ether Substituted Tetrahydrophthalazinones as TbrPDEB1 Inhibitors Following Structure-Based Virtual Screening.Frontiers in chemistry · 2020Article
- Imidazole Derivatives as Promising Agents for the Treatment of Chagas Disease.Antimicrobial agents and chemotherapy · 2019Article
- Screening of a PDE-focused library identifies imidazoles with in vitro and in vivo antischistosomal activity.International journal for parasitology. Drugs and drug resistance · 2019Article
- Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma.Nature communications · 2019Article
- Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite.Frontiers in cellular and infection microbiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of drugs for neglected infectious diseases often uses parasite-specific enzymes as targets. We here demonstrate that parasite enzymes with highly conserved human homologs may represent a promising reservoir of new potential drug targets. The cyclic nucleotide-specific phosphodiesterases (PDEs) of Trypanosoma brucei, causative agent of the fatal human sleeping sickness, are essential for the parasite. The highly conserved human homologs are well-established drug targets. We here describe what is to our knowledge the first pharmacological validation of trypanosomal PDEs as drug targets. High-throughput screening of a proprietary compound library identified a number of potent hits. One compound, the tetrahydrophthalazinone compound A (Cpd A), was further characterized. It causes a dramatic increase of intracellular cyclic adenosine monophosphate (cAMP). Short-term cell viability is not affected, but cell proliferation is inhibited immediately, and cell death occurs within 3 days. Cpd A prevents cytokinesis, resulting in multinucleated, multiflagellated cells that eventually lyse. These observations pharmacologically validate the highly conserved trypanosomal PDEs as potential drug targets.
Indexed as
Identifiers
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.