ArticleChemistry & biology2012
The antimalarial natural product symplostatin 4 is a nanomolar inhibitor of the food vacuole falcipains.
Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 79 citations in OpenAlex.
- Harnessing Phytonanotechnology to Tackle Neglected Parasitic Diseases: Focus on Chagas Disease and Malaria.Pharmaceutics · 2025Review
- The Cyanobacterial Oxadiazine Nocuolin A Shows Broad-Spectrum Toxicity Against Protozoans and the Nematode C. elegans.Microbial ecology · 2025Article
- Marine Natural Products as Novel Treatments for Parasitic Diseases.Handbook of experimental pharmacology · 2025Review
- Marine Cyanobacteria: A Rich Source of Structurally Unique Anti-Infectives for Drug Development.Molecules (Basel, Switzerland) · 2024Review
- Sulfonamide based pyrimidine derivatives combatingRSC advances · 2024Article
- Nature-Inspired Gallinamides Are Potent Antischistosomal Agents: Inhibition of the Cathepsin B1 Protease Target and Binding Mode Analysis.ACS infectious diseases · 2024Article
- Reinvestigation of diphenylmethylpiperazine analogues of pyrazine as new class ofRSC medicinal chemistry · 2024Article
- Three Decades of Targeting Falcipains to Develop Antiplasmodial Agents: What have we Learned and What can be Done Next?Current medicinal chemistry · 2024Review
- Marine organisms as potential sources of natural products for the prevention and treatment of malaria.RSC advances · 2023Review
- Review
- Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L.Journal of medicinal chemistry · 2022Article
- A Mitochondria-Penetrating Peptide Exerts Potent Anti-Plasmodium Activity and Localizes at Parasites' Mitochondria.Antibiotics (Basel, Switzerland) · 2021Article
- Chemoproteomics for Plasmodium Parasite Drug Target Discovery.Chembiochem : a European journal of chemical biology · 2021Review
- Targeting eukaryotic proteases for natural products-based drug development.Natural product reports · 2020Review
- Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets.Molecules (Basel, Switzerland) · 2020Review
- The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms.Marine drugs · 2020Review
- Antiplasmodial natural products: an update.Malaria journal · 2019Review
- Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development ofRSC advances · 2019Article
- Design of Gallinamide A Analogs as Potent Inhibitors of the Cysteine Proteases Human Cathepsin L andJournal of medicinal chemistry · 2019Article
- Natural Products from Cyanobacteria: Focus on Beneficial Activities.Marine drugs · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The marine natural product symplostatin 4 (Sym4) has been recognized as a potent antimalarial agent. However, its mode of action and, in particular, direct targets have to date remained elusive. We report a chemical synthesis of Sym4 and show that Sym4-treatment of P. falciparum-infected red blood cells (RBCs) results in the generation of a swollen food vacuole phenotype and a reduction of parasitemia at nanomolar concentrations. We furthermore demonstrate that Sym4 is a nanomolar inhibitor of the P. falciparum falcipains in infected RBCs, suggesting inhibition of the hemoglobin degradation pathway as Sym4's mode of action. Finally, we reveal a critical influence of the unusual methyl-methoxypyrrolinone (mmp) group of Sym4 for potent inhibition, indicating that Sym4 derivatives with such a mmp moiety might represent viable lead structures for the development of antimalarial falcipain inhibitors.
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.