ArticleMalaria journal2003
The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin.
Article in Malaria journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 104 citations in OpenAlex.
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- Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.Bioorganic & medicinal chemistry · 2025Article
- The possibilities and challenges associated with selective targetingTransactions of the Royal Society of South Africa. Royal Society of South Africa · 2025Article
- Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome.Cell chemical biology · 2024Article
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- Pharmacophore Model-Based Virtual Screening Workflow for Discovery of Inhibitors TargetingACS omega · 2023Article
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Hsp90 and Associated Co-Chaperones of the Malaria Parasite.Biomolecules · 2022Review
- Inhibitors of theCells · 2021Review
- The Role of Hsp70s in the Development and Pathogenicity of Plasmodium falciparum.Advances in experimental medicine and biology · 2021Article
- Heat Shock Proteins as Targets for Novel Antimalarial Drug Discovery.Advances in experimental medicine and biology · 2021Article
- Role of Heat Shock Proteins in Immune Modulation in Malaria.Advances in experimental medicine and biology · 2021Article
- Partners in Mischief: Functional Networks of Heat Shock Proteins ofBiomolecules · 2019Review
- Novobiocin-ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
- HSQC-TOCSY Fingerprinting-Directed Discovery of Antiplasmodial Polyketides from the Marine Ascidian-DerivedMarine drugs · 2018Article
- Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity.Antimicrobial agents and chemotherapy · 2018Article
- Tools for surveillance of anti-malarial drug resistance: an assessment of the current landscape.Malaria journal · 2018Review
- Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed,Frontiers in cellular and infection microbiology · 2018Article
- Identification and characterization of the antiplasmodial activity of Hsp90 inhibitors.Malaria journal · 2017Article
- An integrative analysis of small molecule transcriptional responses in the human malaria parasite Plasmodium falciparum.BMC genomics · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe naturally occurring benzoquinone ansamycin compound, geldanamycin (GA), is a specific inhibitor of heat shock protein 90 (Hsp90) and is a potential anticancer agent. Since Plasmodium falciparum has been reported to have an Hsp90 ortholog, we tested the possibility that GA might inhibit it and thereby display antiparasitic activity.
resultsWe provide direct recombinant DNA evidence for the Hsp90 protein of Plasmodium falciparum, the causative agent of fatal malaria. While the mRNA of Hsp90 was mainly expressed in ring and trophozoite stages, the protein was found in all stages, although schizonts contained relatively lower amounts. In vitro the parasitic Hsp90 exhibited an ATP-binding activity that could be specifically inhibited by GA. Plasmodium growth in human erythrocyte culture was strongly inhibited by GA with an IC50 of 20 nM, compared to the IC50 of 15 nM for chloroquine (CQ) under identical conditions. When used in combination, the two drugs acted synergistically. GA was equally effective against CQ-sensitive and CQ-resistant strains (3D7 and W2, respectively) and on all erythrocytic stages of the parasite.
conclusionsTogether, these results suggest that an active and essential Hsp90 chaperone cycle exists in Plasmodium and that the ansamycin antibiotics will be an important tool to dissect its role in the parasite. Additionally, the favorable pharmacology of GA, reported in human trials, makes it a promising antimalarial drug.
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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.