ArticleAngewandte Chemie (Weinheim an der Bergstrasse, Germany)2016
A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.
Article in Angewandte Chemie (Weinheim an der Bergstrasse, Germany), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 23 citations in OpenAlex.
- Structure-Activity Relationship Study of Antimalarial Asparagine-Derived Proteasome Inhibitors.ACS omega · 2026Article
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
- Chemoproteomics for Plasmodium Parasite Drug Target Discovery.Chembiochem : a European journal of chemical biology · 2021Review
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Artesunate Activation by Heme in an Aqueous Medium.Inorganica chimica acta · 2019Article
- Artemisinin-Based Antimalarial Drug Therapy: Molecular Pharmacology and Evolving Resistance.Tropical medicine and infectious disease · 2019Review
- Inhibition of Cytomegalovirus Replication with Extended-Half-Life Synthetic Ozonides.Antimicrobial agents and chemotherapy · 2019Article
- Enantioselective Synthesis and in Vivo Evaluation of Regioisomeric Analogues of the Antimalarial Arterolane.Journal of medicinal chemistry · 2017Article
- A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2016Article
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 1 country.
Funding
Abstract
In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities.
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.