ArticleAntimicrobial agents and chemotherapy2011
Thiostrepton and derivatives exhibit antimalarial and gametocytocidal activity by dually targeting parasite proteasome and apicoplast.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Ubiquitin-proteasome system inFrontiers in medicine · 2024Pooled it
- Deciphering Membrane Protein Complexes in Plasmodium falciparum Gametocytes via Integrative Structural Systems Biology.Molecular & cellular proteomics : MCP · 2026Article
- BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response.NPJ precision oncology · 2026Article
- Andrographolide as a selective anti-Theileria annulata drug molecule with low host cell cytotoxicity.Tropical animal health and production · 2026Article
- Natural products as transmission-blocking agents against malaria: a comprehensive review of bioactive compounds and their therapeutic potential.Malaria journal · 2025Review
- Ligand-Enabled Selective Coupling of MIDA Boronates to Dehydroalanine-Containing Peptides and Proteins.Journal of the American Chemical Society · 2025Article
- From Traditional Amazon Use to Food Applications:Foods (Basel, Switzerland) · 2025Article
- Thiostrepton: multifaceted biological activities and its applications in treatment of inflammatory diseases.Inflammopharmacology · 2025Review
- Micrococcin cysteine-to-thiazole conversion through transient interactions between the scaffolding protein TclI and the modification enzymes TclJ and TclN.Applied and environmental microbiology · 2024Article
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Article
- An antimicrobial thiopeptide producing novel actinomycetesFEMS microbes · 2023Article
- iAMAP-SCM: A Novel Computational Tool for Large-Scale Identification of Antimalarial Peptides Using Estimated Propensity Scores of Dipeptides.ACS omega · 2022Article
- The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures.BMC biology · 2022Article
- Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides.Chemical reviews · 2022Review
- Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions.Parasites & vectors · 2022Review
- Structural New Data for Mitochondrial Peroxiredoxin FromFrontiers in cellular and infection microbiology · 2022Article
- Targeting Gametocytes of the Malaria ParasitePathogens (Basel, Switzerland) · 2021Review
- Whole genome sequencing ofBiotechnology reports (Amsterdam, Netherlands) · 2021Article
- Thiopeptides: antibiotics with unique chemical structures and diverse biological activities.The Journal of antibiotics · 2021Review
5 more citing papers are in PubMed but not listed here.
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
No grant is acknowledged in the PubMed record.
Abstract
Ribosome-targeting antibiotics exert their antimalarial activity on the apicoplast of the malaria parasite, an organelle of prokaryote origin having essential metabolic functions. These antibiotics typically cause a delayed-death phenotype, which manifests in parasite killing during the second replication cycle following administration. As an exception, treatment with the antibiotic thiostrepton results in an immediate killing. We recently demonstrated that thiostrepton and its derivatives interfere with the eukaryotic proteasome, a multimeric protease complex that is important for the degradation of ubiquitinated proteins. Here, we report that the thiostrepton-based compounds are active against chloroquine-sensitive and -resistant Plasmodium falciparum, where they rapidly eliminate parasites before DNA replication. The minor parasite fraction that escapes the fast killing of the first replication cycle is arrested in the schizont stage of the following cycle, displaying a delayed-death phenotype. Thiostrepton further exhibits gametocytocidal activity by eliminating gametocytes, the sexual precursor cells that are crucial for parasite transmission to the mosquito. Compound treatment results in an accumulation of ubiquitinated proteins in the blood stages, indicating an effect on the parasite proteasome. In accordance with these findings, expression profiling revealed that the proteasome is present in the nucleus and cytoplasm of trophozoites, schizonts, and gametocytes. In conclusion, thiostrepton derivatives represent promising candidates for malaria therapy by dually acting on two independent targets, the parasite proteasome and the apicoplast, with the capacity to eliminate both intraerythrocytic asexual and transmission stages of the parasite.
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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.