ArticleThe Journal of antimicrobial chemotherapy2011
Symmetrical choline-derived dications display strong anti-kinetoplastid activity.
Article in The Journal of antimicrobial chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
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- Multi-target mode of action of a Clerodane-type diterpenoid from Polyalthia longifolia targeting African trypanosomes.Scientific reports · 2018Article
- Targeting Channels and Transporters in Protozoan Parasite Infections.Frontiers in chemistry · 2018Review
- Functional and structural analysis of AT-specific minor groove binders that disrupt DNA-protein interactions and cause disintegration of the Trypanosoma brucei kinetoplast.Nucleic acids research · 2017Article
- The animal trypanosomiases and their chemotherapy: a review.Parasitology · 2016Review
- Reduced Mitochondrial Membrane Potential Is a Late Adaptation of Trypanosoma brucei brucei to Isometamidium Preceded by Mutations in the γ Subunit of the F1Fo-ATPase.PLoS neglected tropical diseases · 2016Article
- Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei.International journal for parasitology. Drugs and drug resistance · 2016Article
- Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes.International journal for parasitology. Drugs and drug resistance · 2015Article
- Targeting the parasite's DNA with methyltriazenyl purine analogs is a safe, selective, and efficacious antitrypanosomal strategy.Antimicrobial agents and chemotherapy · 2015Article
- An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.PLoS pathogens · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesto investigate the anti-kinetoplastid activity of choline-derived analogues with previously reported antimalarial efficacy.
methodsfrom an existing choline analogue library, seven antimalarial compounds, representative of the first-, second- and third-generation analogues previously developed, were assessed for activity against Trypanosoma and Leishmania spp. Using a variety of techniques, the effects of choline analogue exposure on the parasites were documented and a preliminary investigation of their mode of action was performed.
resultsthe activities of choline-derived compounds against Trypanosoma brucei and Leishmania mexicana were determined. The compounds displayed promising anti-kinetoplastid activity, particularly against T. brucei, to which 4/7 displayed submicromolar EC(50) values for the wild-type strain. Low micromolar concentrations of most compounds cleared trypanosome cultures within 24-48 h. The compounds inhibit a choline transporter in Leishmania, but their entry may not depend only on this carrier; T. b. brucei lacks a choline carrier and the mode of uptake remains unclear. The compounds had no effect on the overall lipid composition of the cells, cell cycle progression or cyclic adenosine monophosphate production or short-term effects on intracellular calcium levels. However, several of the compounds, displayed pronounced effects on the mitochondrial membrane potential; this action was not associated with production of reactive oxygen species but rather with a slow rise of intracellular calcium levels and DNA fragmentation.
conclusionsthe choline analogues displayed strong activity against kinetoplastid parasites, particularly against T. b. brucei. In contrast to their antimalarial activity, they did not act on trypanosomes by disrupting choline salvage or phospholipid metabolism, instead disrupting mitochondrial function, leading to chromosomal fragmentation.
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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.