ArticleAntimicrobial agents and chemotherapy2010
Probing the antimalarial mechanism of artemisinin and OZ277 (arterolane) with nonperoxidic isosteres and nitroxyl radicals.
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 29 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
29 citing papers in PubMed, 62 citations in OpenAlex.
- Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol.Malaria journal · 2024Article
- Characterization of antimalarial activity of artemisinin-based hybrid drugs.Antimicrobial agents and chemotherapy · 2024Article
- Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin-proteasome system to kill malaria parasites while overcoming drug resistance.Cell chemical biology · 2023Article
- Antileishmanial Anthracene Endoperoxides: Efficacy In Vitro, Mechanisms and Structure-Activity Relationships.Molecules (Basel, Switzerland) · 2022Article
- Dimeric Artesunate Glycerophosphocholine Conjugate Nano-Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance.Antimicrobial agents and chemotherapy · 2022Article
- Peroxide Antimalarial Drugs Target Redox Homeostasis inACS infectious diseases · 2022Article
- Activation of artemisinin and heme degradation in Leishmania tarentolae promastigotes: A possible link.Biochemical pharmacology · 2020Article
- Inhibition of Cytomegalovirus Replication with Extended-Half-Life Synthetic Ozonides.Antimicrobial agents and chemotherapy · 2019Article
- Activation of Anthracene Endoperoxides inMolecules (Basel, Switzerland) · 2018Article
- New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum.Malaria journal · 2018Article
- Parasite-Mediated Degradation of Synthetic Ozonide Antimalarials ImpactsAntimicrobial agents and chemotherapy · 2018Article
- Article
- In vitro activity of anti-malarial ozonides against an artemisinin-resistant isolate.Malaria journal · 2017Article
- Comparison of the Exposure Time Dependence of the Activities of Synthetic Ozonide Antimalarials and Dihydroartemisinin against K13 Wild-Type and Mutant Plasmodium falciparum Strains.Antimicrobial agents and chemotherapy · 2016Article
- Monoclonal Antibodies That Recognize the Alkylation Signature of Antimalarial Ozonides OZ277 (Arterolane) and OZ439 (Artefenomel).ACS infectious diseases · 2016Article
- In Vitro Susceptibility of Leishmania infantum to Artemisinin Derivatives and Selected Trioxolanes.Antimicrobial agents and chemotherapy · 2015Article
- Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance.PLoS biology · 2015Article
- Efficient and stereocontrolled synthesis of 1,2,4-trioxolanes useful for ferrous iron-dependent drug delivery.Organic letters · 2014Article
- Fixed dose combination of arterolane and piperaquine: a newer prospect in antimalarial therapy.Annals of medical and health sciences research · 2014Review
- Identification and optimization of an aminoalcohol-carbazole series with antimalarial properties.ACS medicinal chemistry letters · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxidic antimalarials such as the semisynthetic artemisinins are critically important in the treatment of drug-resistant malaria. Nevertheless, their peroxide bond-dependent mode of action is still not well understood. Using combination experiments with cultured Plasmodium falciparum cells, we investigated the interactions of the nitroxide radical spin trap, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), and four of its analogs with artemisinin and the ozonide drug development candidate OZ277. The antagonism observed for combinations of artemisinin or OZ277 with the TEMPO analogs supports the hypothesis that the formation of carbon-centered radicals is critical for the activity of these two antimalarial peroxides. The TEMPO analogs showed a trend toward greater antagonism with artemisinin than they did with OZ277, an observation that can be explained by the greater tendency of artemisinin-derived carbon-centered radicals to undergo internal self-quenching reactions, resulting in a lower proportion of radicals available for subsequent chemical reactions such as the alkylation of heme and parasite proteins. In a further mechanistic experiment, we tested both artemisinin and OZ277 in combination with their nonperoxidic analogs. The latter had no effect on the antimalarial activities of the former. These data indicate that the antimalarial properties of peroxides do not derive from reversible interactions with parasite 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.