ArticleAntimicrobial agents and chemotherapy2010
Chemical validation of phosphodiesterase C as a chemotherapeutic target in Trypanosoma cruzi, the etiological agent of Chagas' disease.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Cyclic AMP compartmentalization drives signal specificity to control vector colonization and mammalian host infection by American trypanosomes.PLoS pathogens · 2026Article
- Cyclic AMP compartmentalization drives signal specificity to control vector colonization and mammalian host infection by American trypanosomes.bioRxiv : the preprint server for biology · 2025Article
- Outlining the structure of cAMP compartments in Trypanosoma cruzi.Trends in parasitology · 2025Review
- Article
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- Article
- The old and the new about the contractile vacuole of Trypanosoma cruzi.The Journal of eukaryotic microbiology · 2022Review
- New insights into the role of acidocalcisomes in trypanosomatids.The Journal of eukaryotic microbiology · 2022Review
- Signaling pathways involved in environmental sensing in Trypanosoma cruzi.Molecular microbiology · 2021Review
- Computational approaches for drug discovery against trypanosomatid-caused diseases.Parasitology · 2020Review
- Quantitative Structure-Activity Relationships for Structurally Diverse Chemotypes Having Anti-International journal of molecular sciences · 2019Article
- Cyclic Nucleotide-Specific Phosphodiesterases as Potential Drug Targets for Anti-Leishmania Therapy.Antimicrobial agents and chemotherapy · 2018Article
- Polyphosphate and acidocalcisomes.Biochemical Society transactions · 2016Review
- cAMP signalling in trypanosomatids: role in pathogenesis and as a drug target.Trends in parasitology · 2015Review
- Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure.Journal of medicinal chemistry · 2013Article
- New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists.International review of cell and molecular biology · 2013Review
- Biological and structural characterization of Trypanosoma cruzi phosphodiesterase C and Implications for design of parasite selective inhibitors.The Journal of biological chemistry · 2012Article
- Acidocalcisomes.Cell calcium · 2011Review
- Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite.Future medicinal chemistry · 2011Article
- Target repurposing for neglected diseases.Future medicinal chemistry · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Trypanosoma cruzi phosphodiesterase (PDE) C (TcrPDEC), a novel and rather unusual PDE in which, unlike all other class I PDEs, the catalytic domain is localized in the middle of the polypeptide chain, is able to hydrolyze cyclic GMP (cGMP), although it prefers cyclic AMP (cAMP), and has a FYVE-type domain in its N-terminal region (S. Kunz et al., FEBS J. 272:6412-6422, 2005). TcrPDEC shows homology to the mammalian PDE4 family members. PDE4 inhibitors are currently under development for the treatment of inflammatory diseases, such as asthma, chronic pulmonary diseases, and psoriasis, and for treating depression and serving as cognitive enhancers. We therefore tested a number of compounds originally synthesized as potential PDE4 inhibitors on T. cruzi amastigote growth, and we obtained several useful hits. We then conducted homology modeling of T. cruzi PDEC and identified other compounds as potential inhibitors through virtual screening. Testing of these compounds against amastigote growth and recombinant TcrPDEC activity resulted in several potent inhibitors. The most-potent inhibitors were found to increase the cellular concentration of cAMP. Preincubation of cells in the presence of one of these compounds stimulated volume recovery after hyposmotic stress, in agreement with their TcrPDEC inhibitory activity in vitro, providing chemical validation of this target. The compounds found could be useful tools in the study of osmoregulation in T. cruzi. In addition, their further optimization could result in the development of new drugs against Chagas' disease and other trypanosomiases.
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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.