ArticlePLoS neglected tropical diseases2018
Benzoxaborole treatment perturbs S-adenosyl-L-methionine metabolism in Trypanosoma brucei.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 56 citations in OpenAlex.
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Comparative genome-wide identification and characterization of SET domain-containing and JmjC domain-containing proteins in piroplasms.BMC genomics · 2024Article
- Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024Review
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?Biomolecules · 2023Review
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- Current Treatments to Control African Trypanosomiasis and One Health Perspective.Microorganisms · 2022Review
- Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery.Metabolomics : Official journal of the Metabolomic Society · 2022Review
- Transcriptional differentiation of Trypanosoma brucei during in vitro acquisition of resistance to acoziborole.PLoS neglected tropical diseases · 2021Article
- Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series.Microorganisms · 2021Article
- Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis.Infection and immunity · 2021Review
- Liquid Chromatography-Mass Spectrometry for Clinical Metabolomics: An Overview.Advances in experimental medicine and biology · 2021Article
- Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs.PLoS pathogens · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story.Tropical medicine and infectious disease · 2020Review
- Genomewide Analysis of Mode of Action of themSystems · 2019Article
- Benzimidazole inhibitors of the major cysteine protease ofFuture medicinal chemistry · 2019Article
- Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing.PLoS pathogens · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The parasitic protozoan Trypanosoma brucei causes Human African Trypanosomiasis and Nagana in other mammals. These diseases present a major socio-economic burden to large areas of sub-Saharan Africa. Current therapies involve complex and toxic regimens, which can lead to fatal side-effects. In addition, there is emerging evidence for drug resistance. AN5568 (SCYX-7158) is a novel benzoxaborole class compound that has been selected as a lead compound for the treatment of HAT, and has demonstrated effective clearance of both early and late stage trypanosomiasis in vivo. The compound is currently awaiting phase III clinical trials and could lead to a novel oral therapeutic for the treatment of HAT. However, the mode of action of AN5568 in T. brucei is unknown. This study aimed to investigate the mode of action of AN5568 against T. brucei, using a combination of molecular and metabolomics-based approaches.Treatment of blood-stage trypanosomes with AN5568 led to significant perturbations in parasite metabolism. In particular, elevated levels of metabolites involved in the metabolism of S-adenosyl-L-methionine, an essential methyl group donor, were found. Further comparative metabolomic analyses using an S-adenosyl-L-methionine-dependent methyltransferase inhibitor, sinefungin, showed the presence of several striking metabolic phenotypes common to both treatments. Furthermore, several metabolic changes in AN5568 treated parasites resemble those invoked in cells treated with a strong reducing agent, dithiothreitol, suggesting redox imbalances could be involved in the killing mechanism.
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.